Gary Kelsberg, MD

Evidence summary

There are 3 prospective randomized controlled trials studying the effect of ACE inhibitors on albumin excretion for patients with diabetes who do not have microalbuminuria. A 2-year randomized controlled trial compared lisinopril (Prinivil; Zestril) 10 mg/d with placebo in 530 normotensive adults (aged 20–59 years) with insulin-dependent diabetes, defined as those diagnosed with diabetes before age 36 and using continuous insulin therapy within 1 year of diagnosis. At the beginning of the study, 90 patients had microalbuminuria—defined as an albumin excretion rate (AER) >29 mg/24 hr—and 440 patients did not. When the results for all patients who had and did not have microalbuminuria were combined, there was a significantly smaller rise in the AER for the lisinopril group vs the placebo group (3.2 mg/24 hr lower; P=.03). However, for the patients without initial microalbuminuria, the reduction in the rise of AER with lisinopril was not significant (1.4 mg/24 hr lower; P=.10). The decreased rate of developing new microalbuminuria was also not significant (relative risk reduction [RRR]=12.7%; P=.10).¹

A subsequent trial compared enalapril (Vasotec) 10 mg/d with placebo in 194 normotensive patients (aged 40–60) with type 2 diabetes and without microalbuminuria, defined as AER >30 mg/24 hr. Over the 6-year course of the study, the AER in the placebo group rose from 10.8 mg/24 hr to 26.5 mg/24 hr. The AER of the treatment group dropped from 11.6 mg/24 hr initially to 9.7 mg/24 hr at 2 years, then rose to 15.8 mg/24 hr at 6 years. Enalapril significantly slowed the rise in AER (RRR=0.4; P=.001). Nineteen percent of the placebo group developed microalbuminuria, compared with 6.5% of those taking enalapril (absolute risk reduction[ARR]=12.5%; number needed to treat=8; P=.042). While this study described a modest and statistically significant renal protective effect of enalapril, it did not use an intention-to-treat analysis.²

MICRO-HOPE, a subset of the HOPE trial, studied ramipril (Altace) 10 mg/d vs placebo in 2437 patients with diabetes who did not have clinical proteinuria. Patients were aged 55 years or older and had either a previous cardiovascular event or at least 1 other cardiovascular risk factor. There were 1140 patients with microalbuminuria, defined as an albumin/creatinine ratio 2 mg/mmol, and 2437 patients without. After 4.5 years, 10% of patients had developed overt nephropathy, defined as albumin/creatinine >36 mg/mmol.

When all patients in the study were examined together, ramipril provided significant renal protection over placebo (RRR=24%; ARR=1%; P=.027). It also lowered the risk of MI by 22%, stroke by 33%, and cardiovascular death by 37%. But in a separate analysis of the patients without microalbuminuria, ramipril did not significantly reduce overt nephropathy (P=.50). Ramipril also did not significantly reduce the risk of developing new microalbuminuria in this group (RRR=9%; P=.17). Further, for patients without microalbuminuria, ramipril did not reduce the combined outcomes of myocardial infarction, stroke, or cardiovascular death (odds ratio=0.85; 95% CI, 0.70–1.02).³

Recommendations from others

We could find no guidelines recommending for or against the use of ACE inhibitors for patients with diabetes without microalbuminuria.

Evidence summary

There are 3 prospective randomized controlled trials studying the effect of ACE inhibitors on albumin excretion for patients with diabetes who do not have microalbuminuria. A 2-year randomized controlled trial compared lisinopril (Prinivil; Zestril) 10 mg/d with placebo in 530 normotensive adults (aged 20–59 years) with insulin-dependent diabetes, defined as those diagnosed with diabetes before age 36 and using continuous insulin therapy within 1 year of diagnosis. At the beginning of the study, 90 patients had microalbuminuria—defined as an albumin excretion rate (AER) >29 mg/24 hr—and 440 patients did not. When the results for all patients who had and did not have microalbuminuria were combined, there was a significantly smaller rise in the AER for the lisinopril group vs the placebo group (3.2 mg/24 hr lower; P=.03). However, for the patients without initial microalbuminuria, the reduction in the rise of AER with lisinopril was not significant (1.4 mg/24 hr lower; P=.10). The decreased rate of developing new microalbuminuria was also not significant (relative risk reduction [RRR]=12.7%; P=.10).¹

A subsequent trial compared enalapril (Vasotec) 10 mg/d with placebo in 194 normotensive patients (aged 40–60) with type 2 diabetes and without microalbuminuria, defined as AER >30 mg/24 hr. Over the 6-year course of the study, the AER in the placebo group rose from 10.8 mg/24 hr to 26.5 mg/24 hr. The AER of the treatment group dropped from 11.6 mg/24 hr initially to 9.7 mg/24 hr at 2 years, then rose to 15.8 mg/24 hr at 6 years. Enalapril significantly slowed the rise in AER (RRR=0.4; P=.001). Nineteen percent of the placebo group developed microalbuminuria, compared with 6.5% of those taking enalapril (absolute risk reduction[ARR]=12.5%; number needed to treat=8; P=.042). While this study described a modest and statistically significant renal protective effect of enalapril, it did not use an intention-to-treat analysis.²

MICRO-HOPE, a subset of the HOPE trial, studied ramipril (Altace) 10 mg/d vs placebo in 2437 patients with diabetes who did not have clinical proteinuria. Patients were aged 55 years or older and had either a previous cardiovascular event or at least 1 other cardiovascular risk factor. There were 1140 patients with microalbuminuria, defined as an albumin/creatinine ratio 2 mg/mmol, and 2437 patients without. After 4.5 years, 10% of patients had developed overt nephropathy, defined as albumin/creatinine >36 mg/mmol.

When all patients in the study were examined together, ramipril provided significant renal protection over placebo (RRR=24%; ARR=1%; P=.027). It also lowered the risk of MI by 22%, stroke by 33%, and cardiovascular death by 37%. But in a separate analysis of the patients without microalbuminuria, ramipril did not significantly reduce overt nephropathy (P=.50). Ramipril also did not significantly reduce the risk of developing new microalbuminuria in this group (RRR=9%; P=.17). Further, for patients without microalbuminuria, ramipril did not reduce the combined outcomes of myocardial infarction, stroke, or cardiovascular death (odds ratio=0.85; 95% CI, 0.70–1.02).³

Recommendations from others

We could find no guidelines recommending for or against the use of ACE inhibitors for patients with diabetes without microalbuminuria.

Evidence summary

There are 3 prospective randomized controlled trials studying the effect of ACE inhibitors on albumin excretion for patients with diabetes who do not have microalbuminuria. A 2-year randomized controlled trial compared lisinopril (Prinivil; Zestril) 10 mg/d with placebo in 530 normotensive adults (aged 20–59 years) with insulin-dependent diabetes, defined as those diagnosed with diabetes before age 36 and using continuous insulin therapy within 1 year of diagnosis. At the beginning of the study, 90 patients had microalbuminuria—defined as an albumin excretion rate (AER) >29 mg/24 hr—and 440 patients did not. When the results for all patients who had and did not have microalbuminuria were combined, there was a significantly smaller rise in the AER for the lisinopril group vs the placebo group (3.2 mg/24 hr lower; P=.03). However, for the patients without initial microalbuminuria, the reduction in the rise of AER with lisinopril was not significant (1.4 mg/24 hr lower; P=.10). The decreased rate of developing new microalbuminuria was also not significant (relative risk reduction [RRR]=12.7%; P=.10).¹

A subsequent trial compared enalapril (Vasotec) 10 mg/d with placebo in 194 normotensive patients (aged 40–60) with type 2 diabetes and without microalbuminuria, defined as AER >30 mg/24 hr. Over the 6-year course of the study, the AER in the placebo group rose from 10.8 mg/24 hr to 26.5 mg/24 hr. The AER of the treatment group dropped from 11.6 mg/24 hr initially to 9.7 mg/24 hr at 2 years, then rose to 15.8 mg/24 hr at 6 years. Enalapril significantly slowed the rise in AER (RRR=0.4; P=.001). Nineteen percent of the placebo group developed microalbuminuria, compared with 6.5% of those taking enalapril (absolute risk reduction[ARR]=12.5%; number needed to treat=8; P=.042). While this study described a modest and statistically significant renal protective effect of enalapril, it did not use an intention-to-treat analysis.²

MICRO-HOPE, a subset of the HOPE trial, studied ramipril (Altace) 10 mg/d vs placebo in 2437 patients with diabetes who did not have clinical proteinuria. Patients were aged 55 years or older and had either a previous cardiovascular event or at least 1 other cardiovascular risk factor. There were 1140 patients with microalbuminuria, defined as an albumin/creatinine ratio 2 mg/mmol, and 2437 patients without. After 4.5 years, 10% of patients had developed overt nephropathy, defined as albumin/creatinine >36 mg/mmol.

When all patients in the study were examined together, ramipril provided significant renal protection over placebo (RRR=24%; ARR=1%; P=.027). It also lowered the risk of MI by 22%, stroke by 33%, and cardiovascular death by 37%. But in a separate analysis of the patients without microalbuminuria, ramipril did not significantly reduce overt nephropathy (P=.50). Ramipril also did not significantly reduce the risk of developing new microalbuminuria in this group (RRR=9%; P=.17). Further, for patients without microalbuminuria, ramipril did not reduce the combined outcomes of myocardial infarction, stroke, or cardiovascular death (odds ratio=0.85; 95% CI, 0.70–1.02).³

Recommendations from others

We could find no guidelines recommending for or against the use of ACE inhibitors for patients with diabetes without microalbuminuria.

TABLE
Medications for Parkinson’s disease

Evidence summary

Five randomized controlled trials¹⁵ have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials^1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.⁶ A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.^7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.^11,12 There was no change in off-time with the combination.¹² A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.¹³

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.¹³ There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.^13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.¹⁵ Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.¹⁶ Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.^17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

• selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
• either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
• levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,²⁰ and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).

TABLE
Medications for Parkinson’s disease

Evidence summary

Five randomized controlled trials¹⁵ have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials^1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.⁶ A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.^7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.^11,12 There was no change in off-time with the combination.¹² A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.¹³

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.¹³ There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.^13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.¹⁵ Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.¹⁶ Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.^17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

• selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
• either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
• levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,²⁰ and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).

TABLE
Medications for Parkinson’s disease

Evidence summary

Five randomized controlled trials¹⁵ have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials^1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.⁶ A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.^7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.^11,12 There was no change in off-time with the combination.¹² A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.¹³

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.¹³ There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.^13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.¹⁵ Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.¹⁶ Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.^17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

• selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
• either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
• levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,²⁰ and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).

Evidence summary

Standardized clinical criteria (Table) exist to determine the risk of serious bacterial infection, which includes meningitis; of particular note, these criteria do not require cerebrospinal fluid examination. Infants aged <3 months who fall into the “high-risk” category or appear toxic have 21% probability of a serious bacterial infection, 10% probability of bacteremia, and 2% probability of bacterial meningitis.¹ The “low-risk” infants have a correspondingly lower incidence of serious bacterial infection: the negative predictive value of the Rochester classification is 98.9% (95% confidence interval [CI], 97.2–99.6%).²

The negative predictive value for bacterial meningitis (a subset of serious bacterial infection) is even greater. Five studies applied the standardized criteria to febrile infants and monitored them for the development of serious bacterial infection, including meningitis. Two prospective cohort studies of outpatients aged 0 to 2 months used the Rochester criteria to assign infants to risk groups. They studied a total of 1294 infants; 659 (51%) were low-risk. None of the low-risk infants developed bacterial meningitis.^2,3

One prospective cohort study of infants aged <1 month hospitalized for fever used a similar method for assessing risk, but added a C-reactive protein value <20 mg/L to criteria for low-risk. Of 250 infants studied, 131 (52%) were low-risk; none of these developed bacterial meningitis.⁴

A retrospective chart review of 492 infants aged <3 months who were hospitalized due to fever included 108 infants aged <1 month. Thirty percent (114) of the infants aged 1 to 3 months and 67% (72) of the younger infants underwent lumbar puncture at the discretion of the treating physician. All infants were retrospectively assigned to low- or high-risk groups for serious bacterial infection using the Rochester criteria. Of the 296 infants rated “low-risk,” none developed bacterial meningitis. Ten of these infants subsequently developed evidence of another bacterial focus (predominantly urinary tract infection).⁵

RECOMMENDATIONS FROM OTHERS

The American Academy of Pediatrics has not issued a clinical practice guideline or clinical report addressing this issue. An evidence-based guideline developed at Cincinnati Children’s Hospital Medical Center in 1998 recommends hospitalization and a full sepsis workup (including lumbar puncture) for infants aged <1 month, or infants aged 1 to 2 months who are high-risk.⁶

A clinical review-based guideline published in 1993 gives the same recommendations.⁷ The expert panel that devised this guideline emphasized a full sepsis evaluation (including cerebrospinal fluid cultures) for infants <28 days of age “despite the low probability of serious bacterial infections in this age group and the favorable outcome of the children managed to date with careful observation.” For low-risk infants aged 1 to 2 months, lumbar puncture is not necessary unless empiric antibiotics are given; having a cerebrospinal fluid culture prior to empiric antibiotics reduces the concern of partially treated meningitis in the case of clinical deterioration after hospital discharge.^6,7

TABLE
How to identify infants at low risk of serious bacterial infection: Rochester Classification

Evidence summary

Standardized clinical criteria (Table) exist to determine the risk of serious bacterial infection, which includes meningitis; of particular note, these criteria do not require cerebrospinal fluid examination. Infants aged <3 months who fall into the “high-risk” category or appear toxic have 21% probability of a serious bacterial infection, 10% probability of bacteremia, and 2% probability of bacterial meningitis.¹ The “low-risk” infants have a correspondingly lower incidence of serious bacterial infection: the negative predictive value of the Rochester classification is 98.9% (95% confidence interval [CI], 97.2–99.6%).²

The negative predictive value for bacterial meningitis (a subset of serious bacterial infection) is even greater. Five studies applied the standardized criteria to febrile infants and monitored them for the development of serious bacterial infection, including meningitis. Two prospective cohort studies of outpatients aged 0 to 2 months used the Rochester criteria to assign infants to risk groups. They studied a total of 1294 infants; 659 (51%) were low-risk. None of the low-risk infants developed bacterial meningitis.^2,3

One prospective cohort study of infants aged <1 month hospitalized for fever used a similar method for assessing risk, but added a C-reactive protein value <20 mg/L to criteria for low-risk. Of 250 infants studied, 131 (52%) were low-risk; none of these developed bacterial meningitis.⁴

A retrospective chart review of 492 infants aged <3 months who were hospitalized due to fever included 108 infants aged <1 month. Thirty percent (114) of the infants aged 1 to 3 months and 67% (72) of the younger infants underwent lumbar puncture at the discretion of the treating physician. All infants were retrospectively assigned to low- or high-risk groups for serious bacterial infection using the Rochester criteria. Of the 296 infants rated “low-risk,” none developed bacterial meningitis. Ten of these infants subsequently developed evidence of another bacterial focus (predominantly urinary tract infection).⁵

RECOMMENDATIONS FROM OTHERS

The American Academy of Pediatrics has not issued a clinical practice guideline or clinical report addressing this issue. An evidence-based guideline developed at Cincinnati Children’s Hospital Medical Center in 1998 recommends hospitalization and a full sepsis workup (including lumbar puncture) for infants aged <1 month, or infants aged 1 to 2 months who are high-risk.⁶

A clinical review-based guideline published in 1993 gives the same recommendations.⁷ The expert panel that devised this guideline emphasized a full sepsis evaluation (including cerebrospinal fluid cultures) for infants <28 days of age “despite the low probability of serious bacterial infections in this age group and the favorable outcome of the children managed to date with careful observation.” For low-risk infants aged 1 to 2 months, lumbar puncture is not necessary unless empiric antibiotics are given; having a cerebrospinal fluid culture prior to empiric antibiotics reduces the concern of partially treated meningitis in the case of clinical deterioration after hospital discharge.^6,7

TABLE
How to identify infants at low risk of serious bacterial infection: Rochester Classification

Evidence summary

Standardized clinical criteria (Table) exist to determine the risk of serious bacterial infection, which includes meningitis; of particular note, these criteria do not require cerebrospinal fluid examination. Infants aged <3 months who fall into the “high-risk” category or appear toxic have 21% probability of a serious bacterial infection, 10% probability of bacteremia, and 2% probability of bacterial meningitis.¹ The “low-risk” infants have a correspondingly lower incidence of serious bacterial infection: the negative predictive value of the Rochester classification is 98.9% (95% confidence interval [CI], 97.2–99.6%).²

The negative predictive value for bacterial meningitis (a subset of serious bacterial infection) is even greater. Five studies applied the standardized criteria to febrile infants and monitored them for the development of serious bacterial infection, including meningitis. Two prospective cohort studies of outpatients aged 0 to 2 months used the Rochester criteria to assign infants to risk groups. They studied a total of 1294 infants; 659 (51%) were low-risk. None of the low-risk infants developed bacterial meningitis.^2,3

One prospective cohort study of infants aged <1 month hospitalized for fever used a similar method for assessing risk, but added a C-reactive protein value <20 mg/L to criteria for low-risk. Of 250 infants studied, 131 (52%) were low-risk; none of these developed bacterial meningitis.⁴

A retrospective chart review of 492 infants aged <3 months who were hospitalized due to fever included 108 infants aged <1 month. Thirty percent (114) of the infants aged 1 to 3 months and 67% (72) of the younger infants underwent lumbar puncture at the discretion of the treating physician. All infants were retrospectively assigned to low- or high-risk groups for serious bacterial infection using the Rochester criteria. Of the 296 infants rated “low-risk,” none developed bacterial meningitis. Ten of these infants subsequently developed evidence of another bacterial focus (predominantly urinary tract infection).⁵

RECOMMENDATIONS FROM OTHERS

The American Academy of Pediatrics has not issued a clinical practice guideline or clinical report addressing this issue. An evidence-based guideline developed at Cincinnati Children’s Hospital Medical Center in 1998 recommends hospitalization and a full sepsis workup (including lumbar puncture) for infants aged <1 month, or infants aged 1 to 2 months who are high-risk.⁶

A clinical review-based guideline published in 1993 gives the same recommendations.⁷ The expert panel that devised this guideline emphasized a full sepsis evaluation (including cerebrospinal fluid cultures) for infants <28 days of age “despite the low probability of serious bacterial infections in this age group and the favorable outcome of the children managed to date with careful observation.” For low-risk infants aged 1 to 2 months, lumbar puncture is not necessary unless empiric antibiotics are given; having a cerebrospinal fluid culture prior to empiric antibiotics reduces the concern of partially treated meningitis in the case of clinical deterioration after hospital discharge.^6,7

TABLE
How to identify infants at low risk of serious bacterial infection: Rochester Classification

Evidence summary

Functional braces are designed to provide stability for the unstable knee, but few trials report re-injury rates as an outcome. Cadaver studies show that braces limit tibial rotation and anteroposterior translation. However, the mechanical effects of knee bracing in vivo are controversial.

A study involving 5 patients with chronic unstable ACL injuries showed some limitation of movement with functional bracing, but it was accompanied by slowed muscle performance and used only low-stress forces.¹ Objective findings during physiologic stress loads are inconclusive.²

Three recent randomized controlled trials compared functional bracing with no bracing in rehabilitation after ACL reconstruction. In a prospective study of 62 patients, researchers found no benefit from using a postoperative knee brace at any stage (2 and 6 weeks; 3, 6, and 24 months) after surgery. Moreover, the brace did not contribute to a more stable knee during rehabilitation or 2-year follow-up.³

A similar study of 50 patients demonstrated no significant difference in function or laxity at 2 years.⁴ A 2-year study comparing 30 braced with 30 nonbraced patients showed improved functional stability (P<.05) but increased thigh muscle atrophy (P<.0001) at 3-month follow-up in the braced group. However, no significant differences were seen at other follow-up intervals up to 2 years.⁵

One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace.⁶

RECOMMENDATIONS FROM OTHERS

The American Association of Orthopaedic Surgeons believes that rehabilitative and functional knee braces can be effective in many treatment programs. Rehabilitative braces are more effective in protecting against excessive flexion and extension than against anterior and posterior motion. Functional braces reduce abnormal movement under low load conditions but do not restore normal knee stability under high forces related to certain athletic activities. Physician and patient must guard against a false sense of security.⁷

The American Academy of Pediatrics says that functional braces may help prevent further injury to a previously injured knee. Their use is accepted clinically on the basis of subjective performance. If used, knee braces should complement rehabilitative therapy and required surgery.⁸

Evidence summary

Functional braces are designed to provide stability for the unstable knee, but few trials report re-injury rates as an outcome. Cadaver studies show that braces limit tibial rotation and anteroposterior translation. However, the mechanical effects of knee bracing in vivo are controversial.

A study involving 5 patients with chronic unstable ACL injuries showed some limitation of movement with functional bracing, but it was accompanied by slowed muscle performance and used only low-stress forces.¹ Objective findings during physiologic stress loads are inconclusive.²

Three recent randomized controlled trials compared functional bracing with no bracing in rehabilitation after ACL reconstruction. In a prospective study of 62 patients, researchers found no benefit from using a postoperative knee brace at any stage (2 and 6 weeks; 3, 6, and 24 months) after surgery. Moreover, the brace did not contribute to a more stable knee during rehabilitation or 2-year follow-up.³

A similar study of 50 patients demonstrated no significant difference in function or laxity at 2 years.⁴ A 2-year study comparing 30 braced with 30 nonbraced patients showed improved functional stability (P<.05) but increased thigh muscle atrophy (P<.0001) at 3-month follow-up in the braced group. However, no significant differences were seen at other follow-up intervals up to 2 years.⁵

One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace.⁶

RECOMMENDATIONS FROM OTHERS

The American Association of Orthopaedic Surgeons believes that rehabilitative and functional knee braces can be effective in many treatment programs. Rehabilitative braces are more effective in protecting against excessive flexion and extension than against anterior and posterior motion. Functional braces reduce abnormal movement under low load conditions but do not restore normal knee stability under high forces related to certain athletic activities. Physician and patient must guard against a false sense of security.⁷

The American Academy of Pediatrics says that functional braces may help prevent further injury to a previously injured knee. Their use is accepted clinically on the basis of subjective performance. If used, knee braces should complement rehabilitative therapy and required surgery.⁸

Evidence summary

Functional braces are designed to provide stability for the unstable knee, but few trials report re-injury rates as an outcome. Cadaver studies show that braces limit tibial rotation and anteroposterior translation. However, the mechanical effects of knee bracing in vivo are controversial.

A study involving 5 patients with chronic unstable ACL injuries showed some limitation of movement with functional bracing, but it was accompanied by slowed muscle performance and used only low-stress forces.¹ Objective findings during physiologic stress loads are inconclusive.²

Three recent randomized controlled trials compared functional bracing with no bracing in rehabilitation after ACL reconstruction. In a prospective study of 62 patients, researchers found no benefit from using a postoperative knee brace at any stage (2 and 6 weeks; 3, 6, and 24 months) after surgery. Moreover, the brace did not contribute to a more stable knee during rehabilitation or 2-year follow-up.³

A similar study of 50 patients demonstrated no significant difference in function or laxity at 2 years.⁴ A 2-year study comparing 30 braced with 30 nonbraced patients showed improved functional stability (P<.05) but increased thigh muscle atrophy (P<.0001) at 3-month follow-up in the braced group. However, no significant differences were seen at other follow-up intervals up to 2 years.⁵

One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace.⁶

RECOMMENDATIONS FROM OTHERS

The American Association of Orthopaedic Surgeons believes that rehabilitative and functional knee braces can be effective in many treatment programs. Rehabilitative braces are more effective in protecting against excessive flexion and extension than against anterior and posterior motion. Functional braces reduce abnormal movement under low load conditions but do not restore normal knee stability under high forces related to certain athletic activities. Physician and patient must guard against a false sense of security.⁷

The American Academy of Pediatrics says that functional braces may help prevent further injury to a previously injured knee. Their use is accepted clinically on the basis of subjective performance. If used, knee braces should complement rehabilitative therapy and required surgery.⁸

Evidence summary

Nasal congestion is the most common symptom of the common cold, and hundreds of millions of dollars are spent annually on decongestants. A Cochrane review of 4 randomized controlled trials compared single doses of oxymetazoline, pseudoephedrine, and phenylpropanolamine.¹ Included studies involved from 30 to 106 participants, were double-blinded and placebo-controlled, used either topical or oral decongestants for symptoms of less than 5 days’ duration, and measured either subjective or objective relief or adverse events. All 4 studies used nasal airway resistance as an objective measure of nasal congestion, and a combined symptom score as a subjective measure of relief. One study also administered a side-effect questionnaire.

In all studies, topical and oral decongestants were equally efficacious, producing a 13% reduction in subjective symptoms and a significant decrease in nasal airway resistance after 1 dose of decongestant. Only 1 study investigated repeated doses of decongestants and found no significant additional improvement from repeated doses over a 5-day period.

More studies are needed to evaluate efficacy of multiple doses. Clinical interpretation of these results must take into consideration that quality-of-life measures were not evaluated and that none of the studies included children under 12.

Limited data are available on decongestants in sinusitis. Most studies focused on the use of nasal corticosteroids. One placebo-controlled, randomized controlled trial evaluated the effect on mucociliary clearance from adding nasal saline, nasal steroids, or oxymetazoline to antibiotics in acute bacterial sinusitis.² The group using oxymetazoline increased mucociliary clearance immediately (within 20 minutes). However, at 3 weeks, the improvement in mucociliary clearance in the oxymetazoline group was not significantly different than in the other groups.

An additional prospective, placebo-controlled study evaluated improvement in x-ray findings as well as subjective symptoms in acute sinusitis using phenoxymethyl-penicillin (penicillin V) in combination with oxymetazoline or placebo administered via a variety of nasal delivery systems.³ Oxymetazoline was not significantly different from placebo. Controlled prospective studies are lacking to support the use of decongestants in acute sinusitis.

Recommendations from others

Expert opinion from Current Clinical Topics in Infectious Diseases does not recommend the use of decongestants in sinusitis or the common cold in the absence of concurrent allergic rhinosinusitis.⁴ This recommendation is based on the lack of evidence regarding efficacy and the known rebound congestion associated with topical decongestants. If a decongestant is prescribed, the oral route is preferred, with the understanding of potential significant side effects of nervousness, insomnia, tachycardia, and hypertension.

Evidence summary

Nasal congestion is the most common symptom of the common cold, and hundreds of millions of dollars are spent annually on decongestants. A Cochrane review of 4 randomized controlled trials compared single doses of oxymetazoline, pseudoephedrine, and phenylpropanolamine.¹ Included studies involved from 30 to 106 participants, were double-blinded and placebo-controlled, used either topical or oral decongestants for symptoms of less than 5 days’ duration, and measured either subjective or objective relief or adverse events. All 4 studies used nasal airway resistance as an objective measure of nasal congestion, and a combined symptom score as a subjective measure of relief. One study also administered a side-effect questionnaire.

In all studies, topical and oral decongestants were equally efficacious, producing a 13% reduction in subjective symptoms and a significant decrease in nasal airway resistance after 1 dose of decongestant. Only 1 study investigated repeated doses of decongestants and found no significant additional improvement from repeated doses over a 5-day period.

More studies are needed to evaluate efficacy of multiple doses. Clinical interpretation of these results must take into consideration that quality-of-life measures were not evaluated and that none of the studies included children under 12.

Limited data are available on decongestants in sinusitis. Most studies focused on the use of nasal corticosteroids. One placebo-controlled, randomized controlled trial evaluated the effect on mucociliary clearance from adding nasal saline, nasal steroids, or oxymetazoline to antibiotics in acute bacterial sinusitis.² The group using oxymetazoline increased mucociliary clearance immediately (within 20 minutes). However, at 3 weeks, the improvement in mucociliary clearance in the oxymetazoline group was not significantly different than in the other groups.

An additional prospective, placebo-controlled study evaluated improvement in x-ray findings as well as subjective symptoms in acute sinusitis using phenoxymethyl-penicillin (penicillin V) in combination with oxymetazoline or placebo administered via a variety of nasal delivery systems.³ Oxymetazoline was not significantly different from placebo. Controlled prospective studies are lacking to support the use of decongestants in acute sinusitis.

Recommendations from others

Expert opinion from Current Clinical Topics in Infectious Diseases does not recommend the use of decongestants in sinusitis or the common cold in the absence of concurrent allergic rhinosinusitis.⁴ This recommendation is based on the lack of evidence regarding efficacy and the known rebound congestion associated with topical decongestants. If a decongestant is prescribed, the oral route is preferred, with the understanding of potential significant side effects of nervousness, insomnia, tachycardia, and hypertension.

Evidence summary

Nasal congestion is the most common symptom of the common cold, and hundreds of millions of dollars are spent annually on decongestants. A Cochrane review of 4 randomized controlled trials compared single doses of oxymetazoline, pseudoephedrine, and phenylpropanolamine.¹ Included studies involved from 30 to 106 participants, were double-blinded and placebo-controlled, used either topical or oral decongestants for symptoms of less than 5 days’ duration, and measured either subjective or objective relief or adverse events. All 4 studies used nasal airway resistance as an objective measure of nasal congestion, and a combined symptom score as a subjective measure of relief. One study also administered a side-effect questionnaire.

In all studies, topical and oral decongestants were equally efficacious, producing a 13% reduction in subjective symptoms and a significant decrease in nasal airway resistance after 1 dose of decongestant. Only 1 study investigated repeated doses of decongestants and found no significant additional improvement from repeated doses over a 5-day period.

More studies are needed to evaluate efficacy of multiple doses. Clinical interpretation of these results must take into consideration that quality-of-life measures were not evaluated and that none of the studies included children under 12.

Limited data are available on decongestants in sinusitis. Most studies focused on the use of nasal corticosteroids. One placebo-controlled, randomized controlled trial evaluated the effect on mucociliary clearance from adding nasal saline, nasal steroids, or oxymetazoline to antibiotics in acute bacterial sinusitis.² The group using oxymetazoline increased mucociliary clearance immediately (within 20 minutes). However, at 3 weeks, the improvement in mucociliary clearance in the oxymetazoline group was not significantly different than in the other groups.

An additional prospective, placebo-controlled study evaluated improvement in x-ray findings as well as subjective symptoms in acute sinusitis using phenoxymethyl-penicillin (penicillin V) in combination with oxymetazoline or placebo administered via a variety of nasal delivery systems.³ Oxymetazoline was not significantly different from placebo. Controlled prospective studies are lacking to support the use of decongestants in acute sinusitis.

Recommendations from others

Expert opinion from Current Clinical Topics in Infectious Diseases does not recommend the use of decongestants in sinusitis or the common cold in the absence of concurrent allergic rhinosinusitis.⁴ This recommendation is based on the lack of evidence regarding efficacy and the known rebound congestion associated with topical decongestants. If a decongestant is prescribed, the oral route is preferred, with the understanding of potential significant side effects of nervousness, insomnia, tachycardia, and hypertension.

Evidence summary

Studies of ankle sprain use variable diagnostic criteria for sprain and definition of recovery (return to play). They often report indirect outcomes such as edema. The effect of decreased edema on recovery time is not addressed.

Only 1 study has directly compared heat vs ice therapy and recovery time for ankle sprains. A retrospective cohort study of 32 patients in a sports medicine clinic demonstrated that early cryotherapy (within 36 hours of injury) for grades 3 and 4 ankle sprains, when compared with early heat therapy, resulted in earlier return to activity, as defined by ability to walk, climb stairs, run, and jump without pain.¹ Grade 3 sprains treated with ice recovered in 11.0 days vs 14.8 days with heat. Grade 4 sprains treated with ice recovered in 13.2 days vs 30.4 days with heat. This study also showed that early application of ice (within 36 hours) decreased time to recovery compared with late application of ice.

However, evidence is heterogeneous about the effect of ice on return to play. In 2 of 3 randomized controlled trials, early application of ice vs placebo did not significantly speed return to play.

One randomized controlled trial compared ice therapy (in the form of a cooling anklet applied upon presentation) with placebo in 143 patients presenting within 24 hours of injury to a university emergency department in England.² All patients received high-dose nonsteroidal anti-inflammatory agents. Though a trend was found in favor of ice therapy, no statistically significant difference was found in recovery time, as defined by pain relief and ability to bear weight. The grade of sprain was not specifically accounted for in this study.

Another randomized controlled trial compared ice with placebo in 30 patients with grade 3 and 4 sprains referred to a physiotherapy department within 2 days of ankle injury. No statistical difference was found in recovery time, defined as ability to bear weight with only mild to moderate pain.³

However, a randomized controlled trial of 60 patients with acute ankle sprains of all grades presenting to an emergency department compared cryogel plus bandaging with bandaging alone (cooling vs no cooling). This study found the mean time to recovery—defined as decreased pain—was reduced from 14.8 days to 9.7 days with constant cooling for the first 48 hours.⁴

The application of ice—but not heat—within 24 to 48 hours of acute ankle sprain also reduced edema. Several studies looked at reduction of edema with cooling. One study measured edema in 30 patients with grade 1 and 2 sprains treated with cold, heat, or contrast baths during the third, fourth, and fifth days.⁵ Only ice therapy alone significantly reduced edema.

Recommendations from others

The American Academy of Orthopaedic Surgeons recommends initial treatment of stable ankle sprains with rest, ice, gentle compression, and elevation (RICE).⁶ These guidelines are echoed by the American Academy of Family Physicians. In addition, the Institute for Clinical Systems Improvement and the National Guidelines Clearinghouse recommend PRICE, where protecting the ankle is explicitly added to RICE therapy.⁷

Evidence summary

Studies of ankle sprain use variable diagnostic criteria for sprain and definition of recovery (return to play). They often report indirect outcomes such as edema. The effect of decreased edema on recovery time is not addressed.

Only 1 study has directly compared heat vs ice therapy and recovery time for ankle sprains. A retrospective cohort study of 32 patients in a sports medicine clinic demonstrated that early cryotherapy (within 36 hours of injury) for grades 3 and 4 ankle sprains, when compared with early heat therapy, resulted in earlier return to activity, as defined by ability to walk, climb stairs, run, and jump without pain.¹ Grade 3 sprains treated with ice recovered in 11.0 days vs 14.8 days with heat. Grade 4 sprains treated with ice recovered in 13.2 days vs 30.4 days with heat. This study also showed that early application of ice (within 36 hours) decreased time to recovery compared with late application of ice.

However, evidence is heterogeneous about the effect of ice on return to play. In 2 of 3 randomized controlled trials, early application of ice vs placebo did not significantly speed return to play.

One randomized controlled trial compared ice therapy (in the form of a cooling anklet applied upon presentation) with placebo in 143 patients presenting within 24 hours of injury to a university emergency department in England.² All patients received high-dose nonsteroidal anti-inflammatory agents. Though a trend was found in favor of ice therapy, no statistically significant difference was found in recovery time, as defined by pain relief and ability to bear weight. The grade of sprain was not specifically accounted for in this study.

Another randomized controlled trial compared ice with placebo in 30 patients with grade 3 and 4 sprains referred to a physiotherapy department within 2 days of ankle injury. No statistical difference was found in recovery time, defined as ability to bear weight with only mild to moderate pain.³

However, a randomized controlled trial of 60 patients with acute ankle sprains of all grades presenting to an emergency department compared cryogel plus bandaging with bandaging alone (cooling vs no cooling). This study found the mean time to recovery—defined as decreased pain—was reduced from 14.8 days to 9.7 days with constant cooling for the first 48 hours.⁴

The application of ice—but not heat—within 24 to 48 hours of acute ankle sprain also reduced edema. Several studies looked at reduction of edema with cooling. One study measured edema in 30 patients with grade 1 and 2 sprains treated with cold, heat, or contrast baths during the third, fourth, and fifth days.⁵ Only ice therapy alone significantly reduced edema.

Recommendations from others

The American Academy of Orthopaedic Surgeons recommends initial treatment of stable ankle sprains with rest, ice, gentle compression, and elevation (RICE).⁶ These guidelines are echoed by the American Academy of Family Physicians. In addition, the Institute for Clinical Systems Improvement and the National Guidelines Clearinghouse recommend PRICE, where protecting the ankle is explicitly added to RICE therapy.⁷

Evidence summary

Studies of ankle sprain use variable diagnostic criteria for sprain and definition of recovery (return to play). They often report indirect outcomes such as edema. The effect of decreased edema on recovery time is not addressed.

Only 1 study has directly compared heat vs ice therapy and recovery time for ankle sprains. A retrospective cohort study of 32 patients in a sports medicine clinic demonstrated that early cryotherapy (within 36 hours of injury) for grades 3 and 4 ankle sprains, when compared with early heat therapy, resulted in earlier return to activity, as defined by ability to walk, climb stairs, run, and jump without pain.¹ Grade 3 sprains treated with ice recovered in 11.0 days vs 14.8 days with heat. Grade 4 sprains treated with ice recovered in 13.2 days vs 30.4 days with heat. This study also showed that early application of ice (within 36 hours) decreased time to recovery compared with late application of ice.

However, evidence is heterogeneous about the effect of ice on return to play. In 2 of 3 randomized controlled trials, early application of ice vs placebo did not significantly speed return to play.

One randomized controlled trial compared ice therapy (in the form of a cooling anklet applied upon presentation) with placebo in 143 patients presenting within 24 hours of injury to a university emergency department in England.² All patients received high-dose nonsteroidal anti-inflammatory agents. Though a trend was found in favor of ice therapy, no statistically significant difference was found in recovery time, as defined by pain relief and ability to bear weight. The grade of sprain was not specifically accounted for in this study.

Another randomized controlled trial compared ice with placebo in 30 patients with grade 3 and 4 sprains referred to a physiotherapy department within 2 days of ankle injury. No statistical difference was found in recovery time, defined as ability to bear weight with only mild to moderate pain.³

However, a randomized controlled trial of 60 patients with acute ankle sprains of all grades presenting to an emergency department compared cryogel plus bandaging with bandaging alone (cooling vs no cooling). This study found the mean time to recovery—defined as decreased pain—was reduced from 14.8 days to 9.7 days with constant cooling for the first 48 hours.⁴

The application of ice—but not heat—within 24 to 48 hours of acute ankle sprain also reduced edema. Several studies looked at reduction of edema with cooling. One study measured edema in 30 patients with grade 1 and 2 sprains treated with cold, heat, or contrast baths during the third, fourth, and fifth days.⁵ Only ice therapy alone significantly reduced edema.

Recommendations from others

The American Academy of Orthopaedic Surgeons recommends initial treatment of stable ankle sprains with rest, ice, gentle compression, and elevation (RICE).⁶ These guidelines are echoed by the American Academy of Family Physicians. In addition, the Institute for Clinical Systems Improvement and the National Guidelines Clearinghouse recommend PRICE, where protecting the ankle is explicitly added to RICE therapy.⁷

Evidence summary

Metlay and colleagues¹ found only 4 high-quality, prospective cohort trials evaluating the sensitivity and specificity of the clinical history and physical examination in pneumonia. In each of the 4 studies, the reference standard for the diagnosis of pneumonia was a new infiltrate on chest radiograph. Subjects were community-dwelling adults with acute cough who were seen in ambulatory settings, and who had an average pneumonia prevalence of 7% (range, 3%–38%).¹ Although no study specifically addressed the interobserver reliability of the history and physical examination findings in pneumonia, other studies of chest findings typically found variable reproducibility. In a study by Spiteri and associates,² 24 physicians examined 24 patients with a variety of respiratory conditions: only 4 had pneumonia on chest x-ray. The most reliable findings (dullness to percussion and wheezing) had only fair agreement among examiners (kappa approximately 0.5).

Nine symptoms (cough, dyspnea, sputum production, subjective fever, chills, night sweats, myalgias, sore throat, and rhinorrhea) and 3 items in the past medical history (asthma, immunosuppression, and dementia) were associated with pneumonia. For most elements of history, both the positive and negative likelihood ratios (LR+, LR−) were in the indeterminate range of 0.5 to 2.0. No single feature was sufficient to either rule in or rule out the diagnosis.¹

Regarding the physical examination, tachypnea, tachycardia, and fever had LR+s between 1.5 and 2.4 in an ambulatory setting. In one study, the absence of any vital sign abnormalities reduced the likelihood of pneumonia substantially (LR− = 0.18), but did not rule out the diagnosis completely.¹ Egophony had an LR+ of 5.3. Other physical findings (rhonchi, crackles, decreased breath sounds, dullness to percussion, and bronchial breath sounds) yielded LR+s from 1.5 to 3.5, respectively. Most individual findings were insufficient to diagnose pneumonia. For example, if the baseline prevalence of pneumonia was 5%, the presence of crackles raised the probability to 10% and their absence decreased the probability to 3%.

The sensitivity and specificity of clinical diagnosis varied with the prevalence of pneumonia. In a general practice setting, 20 of 402 patients with cough were diagnosed with pneumonia by chest x-ray.³ Physicians correctly diagnosed 7 patients clinically, and incorrectly diagnosed pneumonia in 22 additional patients.³ At a Veterans Administration hospital, a prospective cohort of 52 men with acute cough and change in sputum production underwent sequential blinded examination by 3 physicians. Rales and bronchial breath sounds were common, and chest x-ray confirmed pneumonia in 28 patients. Sensitivity of clinical diagnosis ranged from 47% to 69%, and specificity from 58% to 75%.⁴

Several researchers improved diagnostic accuracy by combining multiple elements from the history and physical examination. For example, according to Metlay and colleagues,¹ Heckerling et al calculated the probability of pneumonia if up to 5 predictors were present. However, if the prevalence of pneumonia in a primary care population is 5%, the presence of all 5 predictors raises the probability of pneumonia only to 53%.¹ The absence of 4 of the 5 findings (fever >37.8°C, heart rate >100 beats per minute, decreased breath sounds, crackles) reduces the risk of pneumonia to 1%, thus eliminating the need for radiography or antibiotics in most situations. If the patient also has asthma, the risk drops even further.

Recommendations from others

The Infectious Diseases Society of North America states that a chest x-ray is necessary for accurate diagnosis. In otherwise healthy adults with acute cough illness, antibiotic therapy is indicated only for pneumonia. A normal chest x-ray obviates the need for antibiotics.^5,6

Evidence summary

Metlay and colleagues¹ found only 4 high-quality, prospective cohort trials evaluating the sensitivity and specificity of the clinical history and physical examination in pneumonia. In each of the 4 studies, the reference standard for the diagnosis of pneumonia was a new infiltrate on chest radiograph. Subjects were community-dwelling adults with acute cough who were seen in ambulatory settings, and who had an average pneumonia prevalence of 7% (range, 3%–38%).¹ Although no study specifically addressed the interobserver reliability of the history and physical examination findings in pneumonia, other studies of chest findings typically found variable reproducibility. In a study by Spiteri and associates,² 24 physicians examined 24 patients with a variety of respiratory conditions: only 4 had pneumonia on chest x-ray. The most reliable findings (dullness to percussion and wheezing) had only fair agreement among examiners (kappa approximately 0.5).

Nine symptoms (cough, dyspnea, sputum production, subjective fever, chills, night sweats, myalgias, sore throat, and rhinorrhea) and 3 items in the past medical history (asthma, immunosuppression, and dementia) were associated with pneumonia. For most elements of history, both the positive and negative likelihood ratios (LR+, LR−) were in the indeterminate range of 0.5 to 2.0. No single feature was sufficient to either rule in or rule out the diagnosis.¹

Regarding the physical examination, tachypnea, tachycardia, and fever had LR+s between 1.5 and 2.4 in an ambulatory setting. In one study, the absence of any vital sign abnormalities reduced the likelihood of pneumonia substantially (LR− = 0.18), but did not rule out the diagnosis completely.¹ Egophony had an LR+ of 5.3. Other physical findings (rhonchi, crackles, decreased breath sounds, dullness to percussion, and bronchial breath sounds) yielded LR+s from 1.5 to 3.5, respectively. Most individual findings were insufficient to diagnose pneumonia. For example, if the baseline prevalence of pneumonia was 5%, the presence of crackles raised the probability to 10% and their absence decreased the probability to 3%.

The sensitivity and specificity of clinical diagnosis varied with the prevalence of pneumonia. In a general practice setting, 20 of 402 patients with cough were diagnosed with pneumonia by chest x-ray.³ Physicians correctly diagnosed 7 patients clinically, and incorrectly diagnosed pneumonia in 22 additional patients.³ At a Veterans Administration hospital, a prospective cohort of 52 men with acute cough and change in sputum production underwent sequential blinded examination by 3 physicians. Rales and bronchial breath sounds were common, and chest x-ray confirmed pneumonia in 28 patients. Sensitivity of clinical diagnosis ranged from 47% to 69%, and specificity from 58% to 75%.⁴

Several researchers improved diagnostic accuracy by combining multiple elements from the history and physical examination. For example, according to Metlay and colleagues,¹ Heckerling et al calculated the probability of pneumonia if up to 5 predictors were present. However, if the prevalence of pneumonia in a primary care population is 5%, the presence of all 5 predictors raises the probability of pneumonia only to 53%.¹ The absence of 4 of the 5 findings (fever >37.8°C, heart rate >100 beats per minute, decreased breath sounds, crackles) reduces the risk of pneumonia to 1%, thus eliminating the need for radiography or antibiotics in most situations. If the patient also has asthma, the risk drops even further.

Recommendations from others

The Infectious Diseases Society of North America states that a chest x-ray is necessary for accurate diagnosis. In otherwise healthy adults with acute cough illness, antibiotic therapy is indicated only for pneumonia. A normal chest x-ray obviates the need for antibiotics.^5,6

Evidence summary

Metlay and colleagues¹ found only 4 high-quality, prospective cohort trials evaluating the sensitivity and specificity of the clinical history and physical examination in pneumonia. In each of the 4 studies, the reference standard for the diagnosis of pneumonia was a new infiltrate on chest radiograph. Subjects were community-dwelling adults with acute cough who were seen in ambulatory settings, and who had an average pneumonia prevalence of 7% (range, 3%–38%).¹ Although no study specifically addressed the interobserver reliability of the history and physical examination findings in pneumonia, other studies of chest findings typically found variable reproducibility. In a study by Spiteri and associates,² 24 physicians examined 24 patients with a variety of respiratory conditions: only 4 had pneumonia on chest x-ray. The most reliable findings (dullness to percussion and wheezing) had only fair agreement among examiners (kappa approximately 0.5).

Nine symptoms (cough, dyspnea, sputum production, subjective fever, chills, night sweats, myalgias, sore throat, and rhinorrhea) and 3 items in the past medical history (asthma, immunosuppression, and dementia) were associated with pneumonia. For most elements of history, both the positive and negative likelihood ratios (LR+, LR−) were in the indeterminate range of 0.5 to 2.0. No single feature was sufficient to either rule in or rule out the diagnosis.¹

Regarding the physical examination, tachypnea, tachycardia, and fever had LR+s between 1.5 and 2.4 in an ambulatory setting. In one study, the absence of any vital sign abnormalities reduced the likelihood of pneumonia substantially (LR− = 0.18), but did not rule out the diagnosis completely.¹ Egophony had an LR+ of 5.3. Other physical findings (rhonchi, crackles, decreased breath sounds, dullness to percussion, and bronchial breath sounds) yielded LR+s from 1.5 to 3.5, respectively. Most individual findings were insufficient to diagnose pneumonia. For example, if the baseline prevalence of pneumonia was 5%, the presence of crackles raised the probability to 10% and their absence decreased the probability to 3%.

The sensitivity and specificity of clinical diagnosis varied with the prevalence of pneumonia. In a general practice setting, 20 of 402 patients with cough were diagnosed with pneumonia by chest x-ray.³ Physicians correctly diagnosed 7 patients clinically, and incorrectly diagnosed pneumonia in 22 additional patients.³ At a Veterans Administration hospital, a prospective cohort of 52 men with acute cough and change in sputum production underwent sequential blinded examination by 3 physicians. Rales and bronchial breath sounds were common, and chest x-ray confirmed pneumonia in 28 patients. Sensitivity of clinical diagnosis ranged from 47% to 69%, and specificity from 58% to 75%.⁴

Several researchers improved diagnostic accuracy by combining multiple elements from the history and physical examination. For example, according to Metlay and colleagues,¹ Heckerling et al calculated the probability of pneumonia if up to 5 predictors were present. However, if the prevalence of pneumonia in a primary care population is 5%, the presence of all 5 predictors raises the probability of pneumonia only to 53%.¹ The absence of 4 of the 5 findings (fever >37.8°C, heart rate >100 beats per minute, decreased breath sounds, crackles) reduces the risk of pneumonia to 1%, thus eliminating the need for radiography or antibiotics in most situations. If the patient also has asthma, the risk drops even further.

Recommendations from others

The Infectious Diseases Society of North America states that a chest x-ray is necessary for accurate diagnosis. In otherwise healthy adults with acute cough illness, antibiotic therapy is indicated only for pneumonia. A normal chest x-ray obviates the need for antibiotics.^5,6