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Clinical question: Are adjunctive corticosteroids beneficial for patients hospitalized with community-acquired pneumonia (CAP)?

Background: Numerous studies have tried to determine whether or not adjunctive corticosteroids for CAP treatment in hospitalized patients improve outcomes. Although recent trials have suggested that corticosteroids may improve morbidity and mortality, prior meta-analyses have failed to show a benefit, and steroids are not currently routinely recommended for this population.

Study design: Systematic review and meta-analysis of 13 RCTs, predominantly from Europe.

Synopsis: Analysis of 1,974 patients suggested a decrease in all-cause mortality (relative risk (RR) 0.67, 95% CI 0.45-1.01) with adjunctive corticosteroids. Subgroup analysis for severe CAP (six studies, n=388) suggested a greater mortality benefit (RR 0.39, 95% CI 0.2-0.77). There was a decrease in the risk of mechanical ventilation (five studies, n=1060, RR 0.45, CI, 0.26-0.79), ICU admission (three studies, n=950, RR 0.69, 95% CI, 0.46-1.03), and development of acute respiratory distress syndrome (four studies, n=945, RR 0.24, 95% CI 0.10-0.56).

Both hospital length of stay (LOS) and time to clinical stability (hemodynamically stable with no hypoxia) were significantly decreased (mean decrease LOS one day; time to clinical stability 1.22 days). Adverse effects were rare but included increased rates of hyperglycemia requiring treatment (RR 1.49, 95% CI 1.01-2.19). There was no increased frequency of gastrointestinal hemorrhage, neuropsychiatric complications, or rehospitalization.

Bottom line: Adjunctive corticosteroids for inpatient CAP treatment decrease morbidity and mortality, particularly in severe disease, and decrease LOS and time to clinical stability with few adverse reactions.

Citation: Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(7):519-528.

Clinical question: Are adjunctive corticosteroids beneficial for patients hospitalized with community-acquired pneumonia (CAP)?

Background: Numerous studies have tried to determine whether or not adjunctive corticosteroids for CAP treatment in hospitalized patients improve outcomes. Although recent trials have suggested that corticosteroids may improve morbidity and mortality, prior meta-analyses have failed to show a benefit, and steroids are not currently routinely recommended for this population.

Study design: Systematic review and meta-analysis of 13 RCTs, predominantly from Europe.

Synopsis: Analysis of 1,974 patients suggested a decrease in all-cause mortality (relative risk (RR) 0.67, 95% CI 0.45-1.01) with adjunctive corticosteroids. Subgroup analysis for severe CAP (six studies, n=388) suggested a greater mortality benefit (RR 0.39, 95% CI 0.2-0.77). There was a decrease in the risk of mechanical ventilation (five studies, n=1060, RR 0.45, CI, 0.26-0.79), ICU admission (three studies, n=950, RR 0.69, 95% CI, 0.46-1.03), and development of acute respiratory distress syndrome (four studies, n=945, RR 0.24, 95% CI 0.10-0.56).

Both hospital length of stay (LOS) and time to clinical stability (hemodynamically stable with no hypoxia) were significantly decreased (mean decrease LOS one day; time to clinical stability 1.22 days). Adverse effects were rare but included increased rates of hyperglycemia requiring treatment (RR 1.49, 95% CI 1.01-2.19). There was no increased frequency of gastrointestinal hemorrhage, neuropsychiatric complications, or rehospitalization.

Bottom line: Adjunctive corticosteroids for inpatient CAP treatment decrease morbidity and mortality, particularly in severe disease, and decrease LOS and time to clinical stability with few adverse reactions.

Citation: Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(7):519-528.

Clinical question: Are adjunctive corticosteroids beneficial for patients hospitalized with community-acquired pneumonia (CAP)?

Background: Numerous studies have tried to determine whether or not adjunctive corticosteroids for CAP treatment in hospitalized patients improve outcomes. Although recent trials have suggested that corticosteroids may improve morbidity and mortality, prior meta-analyses have failed to show a benefit, and steroids are not currently routinely recommended for this population.

Study design: Systematic review and meta-analysis of 13 RCTs, predominantly from Europe.

Synopsis: Analysis of 1,974 patients suggested a decrease in all-cause mortality (relative risk (RR) 0.67, 95% CI 0.45-1.01) with adjunctive corticosteroids. Subgroup analysis for severe CAP (six studies, n=388) suggested a greater mortality benefit (RR 0.39, 95% CI 0.2-0.77). There was a decrease in the risk of mechanical ventilation (five studies, n=1060, RR 0.45, CI, 0.26-0.79), ICU admission (three studies, n=950, RR 0.69, 95% CI, 0.46-1.03), and development of acute respiratory distress syndrome (four studies, n=945, RR 0.24, 95% CI 0.10-0.56).

Both hospital length of stay (LOS) and time to clinical stability (hemodynamically stable with no hypoxia) were significantly decreased (mean decrease LOS one day; time to clinical stability 1.22 days). Adverse effects were rare but included increased rates of hyperglycemia requiring treatment (RR 1.49, 95% CI 1.01-2.19). There was no increased frequency of gastrointestinal hemorrhage, neuropsychiatric complications, or rehospitalization.

Bottom line: Adjunctive corticosteroids for inpatient CAP treatment decrease morbidity and mortality, particularly in severe disease, and decrease LOS and time to clinical stability with few adverse reactions.

Citation: Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(7):519-528.

Clinical question: How do current Helicobacter pylori treatments compare in efficacy and tolerance?

Background: Efficacy of standard “triple therapy” for H. pylori (proton pump inhibitor plus clarithromycin and amoxicillin or metronidazole) is declining due to the development of antibiotic resistance. Different medication combinations and/or time courses are currently used, but comparative effectiveness of these treatments has not been evaluated comprehensively.

Study design: Systematic review and network meta-analysis.

Setting: Cochrane Library, PubMed, and Embase databases.

Synopsis: One hundred forty-three RCTs evaluating a total of 14 treatments for H. pylori were identified. Network meta-analysis was performed to rank order treatments for efficacy (eradication rate of H. pylori) and tolerance (adverse event occurrence rate). Seven days of “concomitant treatment” (proton pump inhibitor plus three antibiotics) ranked the highest in efficacy (eradication rate 0.94; 95% confidence interval [CI] 0.89-0.98), though this treatment group comprised a very small proportion of overall participants and studies and may be subject to bias. Seven days of standard “triple therapy” ranked the lowest in efficacy (eradication rate 0.73; 95% CI 0.71-0.75).

Of note, subgroup analysis showed variation in efficacy rankings by geographic location, suggesting that findings may not be universally applicable. Only two treatments showed significantly different adverse event occurrence rates compared to standard “triple therapy,” indicating overall similar tolerance for most treatments.

Bottom line: Several treatment regimens may be more effective than standard H. pylori “triple therapy” and equally well tolerated.

Citation: Li BZ, Threapleton DE, Wang JY, et al. Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ. 2015;351:h4052.

Clinical question: How do current Helicobacter pylori treatments compare in efficacy and tolerance?

Background: Efficacy of standard “triple therapy” for H. pylori (proton pump inhibitor plus clarithromycin and amoxicillin or metronidazole) is declining due to the development of antibiotic resistance. Different medication combinations and/or time courses are currently used, but comparative effectiveness of these treatments has not been evaluated comprehensively.

Study design: Systematic review and network meta-analysis.

Setting: Cochrane Library, PubMed, and Embase databases.

Synopsis: One hundred forty-three RCTs evaluating a total of 14 treatments for H. pylori were identified. Network meta-analysis was performed to rank order treatments for efficacy (eradication rate of H. pylori) and tolerance (adverse event occurrence rate). Seven days of “concomitant treatment” (proton pump inhibitor plus three antibiotics) ranked the highest in efficacy (eradication rate 0.94; 95% confidence interval [CI] 0.89-0.98), though this treatment group comprised a very small proportion of overall participants and studies and may be subject to bias. Seven days of standard “triple therapy” ranked the lowest in efficacy (eradication rate 0.73; 95% CI 0.71-0.75).

Of note, subgroup analysis showed variation in efficacy rankings by geographic location, suggesting that findings may not be universally applicable. Only two treatments showed significantly different adverse event occurrence rates compared to standard “triple therapy,” indicating overall similar tolerance for most treatments.

Bottom line: Several treatment regimens may be more effective than standard H. pylori “triple therapy” and equally well tolerated.

Citation: Li BZ, Threapleton DE, Wang JY, et al. Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ. 2015;351:h4052.

Clinical question: How do current Helicobacter pylori treatments compare in efficacy and tolerance?

Background: Efficacy of standard “triple therapy” for H. pylori (proton pump inhibitor plus clarithromycin and amoxicillin or metronidazole) is declining due to the development of antibiotic resistance. Different medication combinations and/or time courses are currently used, but comparative effectiveness of these treatments has not been evaluated comprehensively.

Study design: Systematic review and network meta-analysis.

Setting: Cochrane Library, PubMed, and Embase databases.

Synopsis: One hundred forty-three RCTs evaluating a total of 14 treatments for H. pylori were identified. Network meta-analysis was performed to rank order treatments for efficacy (eradication rate of H. pylori) and tolerance (adverse event occurrence rate). Seven days of “concomitant treatment” (proton pump inhibitor plus three antibiotics) ranked the highest in efficacy (eradication rate 0.94; 95% confidence interval [CI] 0.89-0.98), though this treatment group comprised a very small proportion of overall participants and studies and may be subject to bias. Seven days of standard “triple therapy” ranked the lowest in efficacy (eradication rate 0.73; 95% CI 0.71-0.75).

Of note, subgroup analysis showed variation in efficacy rankings by geographic location, suggesting that findings may not be universally applicable. Only two treatments showed significantly different adverse event occurrence rates compared to standard “triple therapy,” indicating overall similar tolerance for most treatments.

Bottom line: Several treatment regimens may be more effective than standard H. pylori “triple therapy” and equally well tolerated.

Citation: Li BZ, Threapleton DE, Wang JY, et al. Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ. 2015;351:h4052.

Clinical question: What are predictors of primary medication nonadherence after discharge?

Background: Primary nonadherence occurs when a patient receives a prescription at hospital discharge but does not fill it. Predictors of post-discharge primary nonadherence could serve as useful targets to guide adherence interventions.

Study design: RCT, secondary analysis.

Setting: Two tertiary care, U.S. academic hospitals.

Synopsis: Using the Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study database, investigators conducted a secondary analysis of adults hospitalized for acute coronary syndrome or acute decompensated heart failure who received pharmacist-assisted medication reconciliation, discharge counseling, low-literacy adherence aids, and a follow-up phone call. The prevalence of primary nonadherence one to four days post-discharge was 9.4% among 341 patients. In subsequent multivariate analysis, significant factors for noncompliance were living alone (odds ratio 2.2, 95% CI 1.01-4.8, P=0.047) and more than 10 total discharge medications (odds ratio 2.3, 95% CI 1.05-4.98, P=0.036).

Limitations to this study include biases from patient-reported outcomes, lack of patient copayment data, and limited characterization of discharge medication type.

Bottom line: Among patients hospitalized for cardiac events, social isolation and polypharmacy predict primary medication nonadherence to discharge medications despite intensive pharmacist counseling.

Citation: Wooldridge K, Schnipper JL, Goggins K, Dittus RS, Kripalani S. Refractory primary medication nonadherence: prevalence and predictors after pharmacist counseling at hospital discharge [published online ahead of print August 21, 2015]. J Hosp Med. doi: 10.1002/jhm.2446.

Clinical question: What are predictors of primary medication nonadherence after discharge?

Background: Primary nonadherence occurs when a patient receives a prescription at hospital discharge but does not fill it. Predictors of post-discharge primary nonadherence could serve as useful targets to guide adherence interventions.

Study design: RCT, secondary analysis.

Setting: Two tertiary care, U.S. academic hospitals.

Synopsis: Using the Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study database, investigators conducted a secondary analysis of adults hospitalized for acute coronary syndrome or acute decompensated heart failure who received pharmacist-assisted medication reconciliation, discharge counseling, low-literacy adherence aids, and a follow-up phone call. The prevalence of primary nonadherence one to four days post-discharge was 9.4% among 341 patients. In subsequent multivariate analysis, significant factors for noncompliance were living alone (odds ratio 2.2, 95% CI 1.01-4.8, P=0.047) and more than 10 total discharge medications (odds ratio 2.3, 95% CI 1.05-4.98, P=0.036).

Limitations to this study include biases from patient-reported outcomes, lack of patient copayment data, and limited characterization of discharge medication type.

Bottom line: Among patients hospitalized for cardiac events, social isolation and polypharmacy predict primary medication nonadherence to discharge medications despite intensive pharmacist counseling.

Citation: Wooldridge K, Schnipper JL, Goggins K, Dittus RS, Kripalani S. Refractory primary medication nonadherence: prevalence and predictors after pharmacist counseling at hospital discharge [published online ahead of print August 21, 2015]. J Hosp Med. doi: 10.1002/jhm.2446.

Clinical question: What are predictors of primary medication nonadherence after discharge?

Background: Primary nonadherence occurs when a patient receives a prescription at hospital discharge but does not fill it. Predictors of post-discharge primary nonadherence could serve as useful targets to guide adherence interventions.

Study design: RCT, secondary analysis.

Setting: Two tertiary care, U.S. academic hospitals.

Synopsis: Using the Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study database, investigators conducted a secondary analysis of adults hospitalized for acute coronary syndrome or acute decompensated heart failure who received pharmacist-assisted medication reconciliation, discharge counseling, low-literacy adherence aids, and a follow-up phone call. The prevalence of primary nonadherence one to four days post-discharge was 9.4% among 341 patients. In subsequent multivariate analysis, significant factors for noncompliance were living alone (odds ratio 2.2, 95% CI 1.01-4.8, P=0.047) and more than 10 total discharge medications (odds ratio 2.3, 95% CI 1.05-4.98, P=0.036).

Limitations to this study include biases from patient-reported outcomes, lack of patient copayment data, and limited characterization of discharge medication type.

Bottom line: Among patients hospitalized for cardiac events, social isolation and polypharmacy predict primary medication nonadherence to discharge medications despite intensive pharmacist counseling.

Citation: Wooldridge K, Schnipper JL, Goggins K, Dittus RS, Kripalani S. Refractory primary medication nonadherence: prevalence and predictors after pharmacist counseling at hospital discharge [published online ahead of print August 21, 2015]. J Hosp Med. doi: 10.1002/jhm.2446.

Clinical question: Does a patient navigator (PN) who facilitates communication between patients and providers impact hospital length of stay (LOS) and readmissions?

Background: Increasing complexity of hospitalization challenges the safety of care transitions. There are few studies about the effectiveness of innovations targeting both communication and transitional care planning.

Study design: Retrospective, cohort study.

Setting: Single academic health center in Canada, 2010-2014.

Synopsis: PNs, dedicated team-based facilitators not responsible for clinical care, served as liaisons between patients and providers on general medicine teams. They rounded with medical teams, tracked action items, expedited tests and consults, and proactively served as direct primary contacts for patients/families during and after hospitalization. PNs had no specified prior training; they underwent on-the-job training with regular feedback.

Researchers matched 7,841 hospitalizations (5,628 with PN; 2,213 without) by case mix, age, and resource intensity. LOS and 30-day readmissions were primary outcomes. Hospitalizations with PNs were 21% shorter (1.3 days; 6.2 v 7.5 days, P<0.001) than those without PNs.

There were no differences in 30-day readmission rates (13.1 v 13.8%, P=0.48). In this single center study in Canada, the impact of PN salaries (the only program cost) relative to savings is unknown.

Bottom line: Inpatient navigators streamline communication and decrease LOS without increasing readmissions. Additional cost-benefit analyses are needed.

Citation: Kwan JL, Morgan MW, Stewart TE, Bell CM. Impact of an innovative patient navigator program on length of stay and 30-day readmission [published online ahead of print August 10, 2015]. J Hosp Med. doi: 10.1002/jhm.2442.

Clinical question: Does a patient navigator (PN) who facilitates communication between patients and providers impact hospital length of stay (LOS) and readmissions?

Background: Increasing complexity of hospitalization challenges the safety of care transitions. There are few studies about the effectiveness of innovations targeting both communication and transitional care planning.

Study design: Retrospective, cohort study.

Setting: Single academic health center in Canada, 2010-2014.

Synopsis: PNs, dedicated team-based facilitators not responsible for clinical care, served as liaisons between patients and providers on general medicine teams. They rounded with medical teams, tracked action items, expedited tests and consults, and proactively served as direct primary contacts for patients/families during and after hospitalization. PNs had no specified prior training; they underwent on-the-job training with regular feedback.

Researchers matched 7,841 hospitalizations (5,628 with PN; 2,213 without) by case mix, age, and resource intensity. LOS and 30-day readmissions were primary outcomes. Hospitalizations with PNs were 21% shorter (1.3 days; 6.2 v 7.5 days, P<0.001) than those without PNs.

There were no differences in 30-day readmission rates (13.1 v 13.8%, P=0.48). In this single center study in Canada, the impact of PN salaries (the only program cost) relative to savings is unknown.

Bottom line: Inpatient navigators streamline communication and decrease LOS without increasing readmissions. Additional cost-benefit analyses are needed.

Citation: Kwan JL, Morgan MW, Stewart TE, Bell CM. Impact of an innovative patient navigator program on length of stay and 30-day readmission [published online ahead of print August 10, 2015]. J Hosp Med. doi: 10.1002/jhm.2442.

Clinical question: Does a patient navigator (PN) who facilitates communication between patients and providers impact hospital length of stay (LOS) and readmissions?

Background: Increasing complexity of hospitalization challenges the safety of care transitions. There are few studies about the effectiveness of innovations targeting both communication and transitional care planning.

Study design: Retrospective, cohort study.

Setting: Single academic health center in Canada, 2010-2014.

Synopsis: PNs, dedicated team-based facilitators not responsible for clinical care, served as liaisons between patients and providers on general medicine teams. They rounded with medical teams, tracked action items, expedited tests and consults, and proactively served as direct primary contacts for patients/families during and after hospitalization. PNs had no specified prior training; they underwent on-the-job training with regular feedback.

Researchers matched 7,841 hospitalizations (5,628 with PN; 2,213 without) by case mix, age, and resource intensity. LOS and 30-day readmissions were primary outcomes. Hospitalizations with PNs were 21% shorter (1.3 days; 6.2 v 7.5 days, P<0.001) than those without PNs.

There were no differences in 30-day readmission rates (13.1 v 13.8%, P=0.48). In this single center study in Canada, the impact of PN salaries (the only program cost) relative to savings is unknown.

Bottom line: Inpatient navigators streamline communication and decrease LOS without increasing readmissions. Additional cost-benefit analyses are needed.

Citation: Kwan JL, Morgan MW, Stewart TE, Bell CM. Impact of an innovative patient navigator program on length of stay and 30-day readmission [published online ahead of print August 10, 2015]. J Hosp Med. doi: 10.1002/jhm.2442.

Clinical question: In children hospitalized in a non-ICU setting with asthma exacerbation, how effective is dexamethasone compared to prednisone/prednisolone?

Background: Asthma is the second most common reason for hospital admission in childhood.¹ National guidelines recommend treatment with systemic corticosteroids in addition to beta-agonists.² Traditionally, prednisone/prednisolone has been used for asthma exacerbations, but multiple recent studies in ED settings have shown equal efficacy with dexamethasone for mild to moderate exacerbations. Benefits of dexamethasone use include a longer half-life (so single dose or two-day courses can be used), good enteral absorption, general palatability, less emesis, and better adherence. To this point, no studies have compared dexamethasone with prednisone/prednisolone therapy in hospitalized children.

Study design: Multicenter, retrospective cohort study.

Setting: Freestanding, tertiary care children’s hospitals.

Synopsis: The authors used the PHIS (Pediatric Health Information System) database, which includes clinical and billing data from 42 children’s hospitals, to compare children who received dexamethasone to those who were treated with prednisone/prednisolone therapy for asthma exacerbations in the inpatient setting. Patients were included if they were aged four to 17 years, were hospitalized between January 2007 and December 2012 with ICD-9 code for a principal diagnosis of asthma, and received either dexamethasone or prednisone/prednisolone.

Exclusion criteria included:

• Management in the ICU at the time of admission;
• All patient refined diagnosis related groups (APR-DRG) severity level moderate or extreme;
• Complex chronic conditions;
• Secondary diagnosis other than asthma requiring steroids, or treatment with racemic epinephrine;
• Only the first admission was included out of multiple hospitalizations within a 30-day period; and/or
• Patient was treated with both dexamethasone and prednisone/prednisolone.

The primary outcome evaluated was length of stay (LOS); secondary outcomes included readmissions, cost, and transfer to ICU during hospitalization. The authors compared the overall groups, then performed 1:1 propensity score matching to address residual confounding; this statistical technique closely matches patient characteristics between cohorts.

Overall, there were 40,257 hospitalizations, with 1,166 children (2.9%) receiving dexamethasone and 39,091 (97.1%) receiving prednisone/prednisolone. The use of dexamethasone varied greatly between hospitals (35/42 hospitals used dexamethasone, with rates ranging from 0.047% to 77.4%).

In the post-match cohort, 1,284 patients were evaluated, 642 in each group. In this cohort, patients with dexamethasone had significantly shorter LOS (67.4% had LOS less than one day vs. 59.5% in the prednisone/prednisolone group; 6.7% of dexamethasone patients had LOS of more than three days vs. 12% of prednisone/prednisolone patients). Costs were lower for the dexamethasone group, both for the index admission and for episode admission (defined as index admission plus seven-day readmissions). There was no difference in readmissions between the groups, and no patients in this cohort were transferred to the ICU.

There are several limitations to this study. Dexamethasone use varied widely among participating hospitals. The data source did not permit access to dosing, duration, or compliance with therapy and could not compare albuterol use between groups. The findings may not be generalizable to all populations, because it excluded patients with high severity and medical complexity and only evaluated tertiary care children’s hospitals.

Bottom line: Dexamethasone is a potential alternative therapy for asthma exacerbations in the inpatient setting. Further studies are needed to evaluate effectiveness, including dosing, frequency, and duration.

Citation: Parikh K, Hall M, Mittal V, et al. Comparative effectiveness of dexamethasone versus prednisone in children hospitalized with asthma. J Pediatr. 2015;167(3):639-644.

---

Dr. Galloway is a pediatric hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D., assistant professor of pediatrics at the University of South Dakota Sanford School of Medicine, and vice chief of the division of hospital pediatrics at USD SSOM and Sanford Children’s Hospital.

 

References

1. Yu H, Wier LM, Elixhauser A. Hospital stays for children, 2009. HCUP statistical brief #118. Agency for Healthcare Research and Quality. August 2011. Accessed November 1, 2015.
2. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma–Summary Report 2007. Accessed November 1, 2015.

Clinical question: In children hospitalized in a non-ICU setting with asthma exacerbation, how effective is dexamethasone compared to prednisone/prednisolone?

Background: Asthma is the second most common reason for hospital admission in childhood.¹ National guidelines recommend treatment with systemic corticosteroids in addition to beta-agonists.² Traditionally, prednisone/prednisolone has been used for asthma exacerbations, but multiple recent studies in ED settings have shown equal efficacy with dexamethasone for mild to moderate exacerbations. Benefits of dexamethasone use include a longer half-life (so single dose or two-day courses can be used), good enteral absorption, general palatability, less emesis, and better adherence. To this point, no studies have compared dexamethasone with prednisone/prednisolone therapy in hospitalized children.

Study design: Multicenter, retrospective cohort study.

Setting: Freestanding, tertiary care children’s hospitals.

Synopsis: The authors used the PHIS (Pediatric Health Information System) database, which includes clinical and billing data from 42 children’s hospitals, to compare children who received dexamethasone to those who were treated with prednisone/prednisolone therapy for asthma exacerbations in the inpatient setting. Patients were included if they were aged four to 17 years, were hospitalized between January 2007 and December 2012 with ICD-9 code for a principal diagnosis of asthma, and received either dexamethasone or prednisone/prednisolone.

Exclusion criteria included:

• Management in the ICU at the time of admission;
• All patient refined diagnosis related groups (APR-DRG) severity level moderate or extreme;
• Complex chronic conditions;
• Secondary diagnosis other than asthma requiring steroids, or treatment with racemic epinephrine;
• Only the first admission was included out of multiple hospitalizations within a 30-day period; and/or
• Patient was treated with both dexamethasone and prednisone/prednisolone.

The primary outcome evaluated was length of stay (LOS); secondary outcomes included readmissions, cost, and transfer to ICU during hospitalization. The authors compared the overall groups, then performed 1:1 propensity score matching to address residual confounding; this statistical technique closely matches patient characteristics between cohorts.

Overall, there were 40,257 hospitalizations, with 1,166 children (2.9%) receiving dexamethasone and 39,091 (97.1%) receiving prednisone/prednisolone. The use of dexamethasone varied greatly between hospitals (35/42 hospitals used dexamethasone, with rates ranging from 0.047% to 77.4%).

In the post-match cohort, 1,284 patients were evaluated, 642 in each group. In this cohort, patients with dexamethasone had significantly shorter LOS (67.4% had LOS less than one day vs. 59.5% in the prednisone/prednisolone group; 6.7% of dexamethasone patients had LOS of more than three days vs. 12% of prednisone/prednisolone patients). Costs were lower for the dexamethasone group, both for the index admission and for episode admission (defined as index admission plus seven-day readmissions). There was no difference in readmissions between the groups, and no patients in this cohort were transferred to the ICU.

There are several limitations to this study. Dexamethasone use varied widely among participating hospitals. The data source did not permit access to dosing, duration, or compliance with therapy and could not compare albuterol use between groups. The findings may not be generalizable to all populations, because it excluded patients with high severity and medical complexity and only evaluated tertiary care children’s hospitals.

Bottom line: Dexamethasone is a potential alternative therapy for asthma exacerbations in the inpatient setting. Further studies are needed to evaluate effectiveness, including dosing, frequency, and duration.

Citation: Parikh K, Hall M, Mittal V, et al. Comparative effectiveness of dexamethasone versus prednisone in children hospitalized with asthma. J Pediatr. 2015;167(3):639-644.

---

Dr. Galloway is a pediatric hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D., assistant professor of pediatrics at the University of South Dakota Sanford School of Medicine, and vice chief of the division of hospital pediatrics at USD SSOM and Sanford Children’s Hospital.

 

References

1. Yu H, Wier LM, Elixhauser A. Hospital stays for children, 2009. HCUP statistical brief #118. Agency for Healthcare Research and Quality. August 2011. Accessed November 1, 2015.
2. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma–Summary Report 2007. Accessed November 1, 2015.

Clinical question: In children hospitalized in a non-ICU setting with asthma exacerbation, how effective is dexamethasone compared to prednisone/prednisolone?

Background: Asthma is the second most common reason for hospital admission in childhood.¹ National guidelines recommend treatment with systemic corticosteroids in addition to beta-agonists.² Traditionally, prednisone/prednisolone has been used for asthma exacerbations, but multiple recent studies in ED settings have shown equal efficacy with dexamethasone for mild to moderate exacerbations. Benefits of dexamethasone use include a longer half-life (so single dose or two-day courses can be used), good enteral absorption, general palatability, less emesis, and better adherence. To this point, no studies have compared dexamethasone with prednisone/prednisolone therapy in hospitalized children.

Study design: Multicenter, retrospective cohort study.

Setting: Freestanding, tertiary care children’s hospitals.

Synopsis: The authors used the PHIS (Pediatric Health Information System) database, which includes clinical and billing data from 42 children’s hospitals, to compare children who received dexamethasone to those who were treated with prednisone/prednisolone therapy for asthma exacerbations in the inpatient setting. Patients were included if they were aged four to 17 years, were hospitalized between January 2007 and December 2012 with ICD-9 code for a principal diagnosis of asthma, and received either dexamethasone or prednisone/prednisolone.

Exclusion criteria included:

• Management in the ICU at the time of admission;
• All patient refined diagnosis related groups (APR-DRG) severity level moderate or extreme;
• Complex chronic conditions;
• Secondary diagnosis other than asthma requiring steroids, or treatment with racemic epinephrine;
• Only the first admission was included out of multiple hospitalizations within a 30-day period; and/or
• Patient was treated with both dexamethasone and prednisone/prednisolone.

The primary outcome evaluated was length of stay (LOS); secondary outcomes included readmissions, cost, and transfer to ICU during hospitalization. The authors compared the overall groups, then performed 1:1 propensity score matching to address residual confounding; this statistical technique closely matches patient characteristics between cohorts.

Overall, there were 40,257 hospitalizations, with 1,166 children (2.9%) receiving dexamethasone and 39,091 (97.1%) receiving prednisone/prednisolone. The use of dexamethasone varied greatly between hospitals (35/42 hospitals used dexamethasone, with rates ranging from 0.047% to 77.4%).

In the post-match cohort, 1,284 patients were evaluated, 642 in each group. In this cohort, patients with dexamethasone had significantly shorter LOS (67.4% had LOS less than one day vs. 59.5% in the prednisone/prednisolone group; 6.7% of dexamethasone patients had LOS of more than three days vs. 12% of prednisone/prednisolone patients). Costs were lower for the dexamethasone group, both for the index admission and for episode admission (defined as index admission plus seven-day readmissions). There was no difference in readmissions between the groups, and no patients in this cohort were transferred to the ICU.

There are several limitations to this study. Dexamethasone use varied widely among participating hospitals. The data source did not permit access to dosing, duration, or compliance with therapy and could not compare albuterol use between groups. The findings may not be generalizable to all populations, because it excluded patients with high severity and medical complexity and only evaluated tertiary care children’s hospitals.

Bottom line: Dexamethasone is a potential alternative therapy for asthma exacerbations in the inpatient setting. Further studies are needed to evaluate effectiveness, including dosing, frequency, and duration.

Citation: Parikh K, Hall M, Mittal V, et al. Comparative effectiveness of dexamethasone versus prednisone in children hospitalized with asthma. J Pediatr. 2015;167(3):639-644.

---

Dr. Galloway is a pediatric hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D., assistant professor of pediatrics at the University of South Dakota Sanford School of Medicine, and vice chief of the division of hospital pediatrics at USD SSOM and Sanford Children’s Hospital.

 

References

1. Yu H, Wier LM, Elixhauser A. Hospital stays for children, 2009. HCUP statistical brief #118. Agency for Healthcare Research and Quality. August 2011. Accessed November 1, 2015.
2. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma–Summary Report 2007. Accessed November 1, 2015.

Case

Mr. G is an 80-year-old man with a pacemaker, peripheral artery disease, atrial fibrillation (AF) on warfarin, and tachy-brady syndrome. He presented after experiencing episodes in which he was unable to speak and had weakness on his right side. He had a normal neurological exam upon arrival to the ED, and his blood pressure was 160/80 mm Hg.

Overview

Transient ischemic attacks (TIAs) are brief interruptions in brain perfusion that do not result in permanent neurologic damage. Up to half a million TIAs occur each year in the U.S., and they account for one third of acute cerebrovascular disease.1 While the term suggests that TIAs are benign, they are in fact an important warning sign of impending stroke and are essentially analogous to unstable angina. Some 10% of TIAs convert to full strokes within 90 days, but growing evidence suggests appropriate interventions can decrease this risk to 3%.²

Unfortunately, the symptoms of TIA have usually resolved by the time patients arrive at the hospital, which makes them challenging to diagnose. This article provides a summary of how to diagnose TIA accurately, using a focused history informed by cerebrovascular localization; how to triage, evaluate, and risk stratify patients; and how to implement preventative strategies.

Review of the Data

Classically, TIAs are defined as lasting less than 24 hours; however, 24 hours is an arbitrary number, and most TIAs last less than one hour.¹ Furthermore, this definition has evolved with advances in neuroimaging that reveal that up to 50% of classically defined TIAs have evidence of infarct on MRI.¹ There is no absolute temporal cut-off after which infarct is always seen on MRI, but longer duration of symptoms correlates with a higher likelihood of infarct. To reconcile these observations, a recently proposed definition stipulates that a true TIA lasts no more than one hour and does not show evidence of infarct on MRI.³

The causes of TIA are identical to those for ischemic stroke. Cerebral ischemia can result from an embolus, arterial thrombosis, or hypoperfusion due to arterial stenosis. Emboli can be cardiac, most commonly due to AF, or non-cardiac, stemming from a ruptured atherosclerotic plaque in the aortic arch, the carotid or vertebral artery, or an intracranial vessel. Atherosclerotic disease in the carotid arteries or intracranial vessels can also lead to thrombosis and occlusion or flow-related TIAs as a result of severe stenosis.

Risk factors for TIA mirror those for heart disease. Non-modifiable risk factors include older age, black race, male sex, and family history of stroke. Modifiable factors include hypertension, hyperlipidemia, tobacco smoking, diabetes, and AF.⁴

Most of the time, patients’ symptoms will have resolved by the time they are evaluated by a physician. Therefore, the diagnosis of TIA relies almost exclusively on the patient history. Eliciting a good history helps physicians determine whether the episode of transient neurologic dysfunction was caused by cerebral ischemia, as opposed to another mechanism, such as migraine or seizure. This calls for a basic understanding of cerebrovascular anatomy (see Table 1).

Types of Ischemia

Anterior cerebral artery ischemia causes contralateral leg weakness because it supplies the medial frontal and parietal lobes, where the legs in the sensorimotor homunculus are represented. Middle cerebral artery (MCA) ischemia causes contralateral face and arm weakness out of proportion to leg weakness. Ischemia in Broca’s area of the brain, which is supplied by the left MCA, may also cause expressive aphasia. Transient monocular blindness is a TIA of the retina due to atheroemboli originating from the internal carotid artery. Vertebrobasilar TIA is less common than anterior circulation TIA and manifests with brainstem symptoms that include diplopia, dysarthria, dysphagia, vertigo, gait imbalance, and weakness. In general, language and motor symptoms are more specific for cerebral ischemia and therefore more worrisome for TIA than sensory symptoms.⁵

 

Once a clinical diagnosis of TIA is made, an ABCD2 score (age, blood pressure, clinical features, duration of TIA, presence of diabetes) can be used to predict the short-term risk of subsequent stroke (see Table 2).^6,7 A general rule of thumb is to admit patients who present within 72 hours of the event and have an ABCD2 score of three or higher for observation, work-up, and initiation of secondary prevention.¹

Although only a small percentage of patients with TIA will have a stroke during the period of observation in the hospital, this approach may be cost effective based on the assumption that hospitalized patients are more likely to receive intravenous tissue plasminogen activator.⁸ The decision should also be guided by clinical judgment. It is reasonable to admit a patient whose diagnostic workup cannot be rapidly completed.¹

The workup for TIA includes routine labs, EKG with cardiac monitoring, and brain imaging. Labs are useful to evaluate for other mimics of TIA such as hyponatremia and glucose abnormalities. In addition, risk factors such as hyperlipidemia and diabetes should be evaluated with fasting lipid panel and blood glucose. The purpose of EKG and telemetry is to identify MI and capture paroxysmal AF. The goal of imaging is to ascertain the presence of vascular disease and to exclude a non-ischemic etiology. While less likely to cause transient neurologic symptoms, a hemorrhagic event must be ruled out, as it would trigger a different management pathway.

Imaging for TIA

There are two primary modes of brain imaging: computed tomography (CT) and MRI. Most patients who are suspected to have had a TIA undergo CT scan, and an infarct is seen about 20% of the time.¹ The presence of an infarct usually correlates with the duration of symptoms and has prognostic value. In one study, a new infarct was associated with four times higher risk of stroke in the subsequent 90 days.⁹ Diffusion-weighted imaging, an MR-based technique, is the preferred modality when it is available because of its higher sensitivity and specificity for identifying acute lesions.¹ In an international and multicenter study, incorporating imaging data increased the discriminatory power of stroke prediction.¹⁰

Extracranial imaging is mandatory to rule out carotid stenosis as a potential etiology of TIA. The least invasive modality is ultrasound, which can detect carotid stenosis with a sensitivity and specificity approaching 80%.¹ While both the intra- and extracranial vasculature can be concurrently assessed using MR- or CT-angiography (CTA), this is not usually necessary in the acute setting, because only detecting carotid stenosis will result in a management change.¹

Carotid endarterectomy is standard for symptomatic patients with greater than 70% stenosis and is a consideration for symptomatic patients with greater than 50% stenosis if it is the most probable explanation for the ischemic event.¹¹ Despite a comprehensive workup, about 50% of TIA cases remain cryptogenic.¹² In some of these patients, AF can be detected using extended ambulatory cardiac monitoring.¹²

The goal of admitting high-risk patients is to expedite workup and initiate therapy. Two studies have shown that immediate initiation of preventative treatment significantly reduces the risk of stroke by as much as 80%.^13,14 Unless there is a specific indication for anticoagulation, all TIA patients should be started on an antiplatelet agent such as aspirin or clopidogrel. A large randomized trial conducted in China and published in 2013 demonstrated that dual antiplatelet therapy with aspirin and clopidogrel for 21 days, followed by clopidogrel monotherapy, reduced the risk of stroke compared to aspirin monotherapy. An international multicenter trial designed to test the efficacy of short-term dual antiplatelet therapy is ongoing, and if the benefit of this approach is confirmed, this will likely become the standard of care. Evidence-based indications for anticoagulation after TIA are restricted to AF and mural thrombus in the setting of recent MI. Patients with implanted mechanical devices, including left ventricular assist devices and metal heart valves, should also receive anticoagulation.¹⁵

 

Risk factors should also be targeted in every case. Hypertension should be treated with a goal of lower than 140/90 mm Hg (or 130/80 mm Hg in diabetics and those with renal disease). Studies have shown that patients who are discharged with a blood pressure lower than 140/90 mm Hg are more likely to maintain this blood pressure at one-year follow-up.¹⁶ The choice of medication is less well studied, but drugs that act on the renin-angiotensin-aldosterone system and thiazides are generally preferred.¹⁵ Treatment with a statin is recommended after cerebrovascular ischemic events, with a goal LDL under 100. This reduces risk of secondary stroke by about 20%.¹⁷

At discharge, it is also important to counsel patients on their role in preventing strokes. As with many diseases, making lifestyle changes is key to stroke prevention. Encourage smoking cessation and an increase in physical activity, and discourage heavy alcohol use. The association between smoking and the risk for first stroke is well established. Moderate to high-intensity exercise can reduce secondary stroke risk by as much as 50%¹⁸ (see Table 3). While light alcohol consumption can be protective against strokes, heavy use is strongly discouraged. Emerging data suggest obstructive sleep apnea (OSA) may be another modifiable risk factor for stroke and TIA, so screening for potential OSA and referral may be needed.¹⁵

Back to the Case

When Mr. G arrived at the ED, his symptoms had resolved. Based on the history of expressive aphasia and right-sided weakness, he most likely had a TIA in the left MCA territory. Hemorrhage was ruled out with a non-contrast head CT. His pacemaker precluded obtaining an MRI. CTA revealed diffuse atherosclerotic disease without evidence of carotid stenosis. His ABCD2 score was six given his age, blood pressure, weakness, and symptom duration, and he was admitted for an expedited workup. His sodium and glucose were within normal limits. His hemoglobin A1c was 6.5%, his LDL was 120, and his international normalized ratio (INR) was therapeutic at 2.1. His TIA may have been due to AF, despite a therapeutic INR, because warfarin does not fully eliminate the stroke risk. It might also have been caused by intracranial atherosclerosis.

Two days later, the patient was discharged on atorvastatin at 80 mg, and his lisinopril was increased for blood pressure control. For his age group, A1c of 6.5% was acceptable, and he was not initiated on glycemic control.

Bottom Line

TIAs are diagnosed based on patient history. Urgent initiation of secondary prevention is important to reduce the short-term risk of stroke and should be implemented by the time of discharge from the hospital.

---

Dr. Zeng is a hospitalist in the department of internal medicine at Vanderbilt University Medical Center in Nashville, and Dr. Douglas is associate professor in the department of neurology at the University of California at San Francisco.

 

References

1. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009;40(6):2276-2293.
2. Sundararajan V, Thrift AG, Phan TG, Choi PM, Clissold B, Srikanth VK. Trends over time in the risk of stroke after an incident transient ischemic attack. Stroke. 2014;45(11):3214-3218.
3. Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack–proposal for a new definition. N Engl J Med. 2002;347(21):1713-1716.
4. Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin. 2008;26(4):871-895, vii.
5. Johnston SC, Sidney S, Bernstein AL, Gress DR. A comparison of risk factors for recurrent TIA and stroke in patients diagnosed with TIA. Neurology. 2003;60(2):280-285.
6. Tsivgoulis G, Stamboulis E, Sharma VK, et al. Multicenter external validation of the ABCD2 score in triaging TIA patients. Neurology. 2010;74(17):1351-1357.
7. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369(9558):283-292.
8. Nguyen-Huynh MN, Johnston SC. Is hospitalization after TIA cost-effective on the basis of treatment with tPA? Neurology. 2005;65(11):1799-1801.
9. Douglas VC, Johnston CM, Elkins J, Sidney S, Gress DR, Johnston SC. Head computed tomography findings predict short-term stroke risk after transient ischemic attack. Stroke. 2003;34(12):2894-2898.
10. Giles MF, Albers GW, Amarenco P, et al. Addition of brain infarction to the ABCD2 Score (ABCD2I): a collaborative analysis of unpublished data on 4574 patients. Stroke. 2010;41(9):1907-1913.
11. Lanzino G, Rabinstein AA, Brown RD Jr. Treatment of carotid artery stenosis: medical therapy, surgery, or stenting? Mayo Clin Proc. 2009;84(4):362-387; quiz 367-368.
12. Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370(26):2467-2477.
13. Lavallée PC, Meseguer E, Abboud H, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007;6(11):953-960.
14. Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007;370(9596):1432-1442.
15. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-2236.
16. Roumie CL, Zillich AJ, Bravata DM, et al. Hypertension treatment intensification among stroke survivors with uncontrolled blood pressure. Stroke. 2015;46(2):465-470.
17. Amarenco P, Bogousslavsky J, Callahan A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559.
18. Lennon O, Galvin R, Smith K, Doody C, Blake C. Lifestyle interventions for secondary disease prevention in stroke and transient ischaemic attack: a systematic review. Eur J Prev Cardiol. 2014;21(8):1026-1039.

Case

Mr. G is an 80-year-old man with a pacemaker, peripheral artery disease, atrial fibrillation (AF) on warfarin, and tachy-brady syndrome. He presented after experiencing episodes in which he was unable to speak and had weakness on his right side. He had a normal neurological exam upon arrival to the ED, and his blood pressure was 160/80 mm Hg.

Overview

Transient ischemic attacks (TIAs) are brief interruptions in brain perfusion that do not result in permanent neurologic damage. Up to half a million TIAs occur each year in the U.S., and they account for one third of acute cerebrovascular disease.1 While the term suggests that TIAs are benign, they are in fact an important warning sign of impending stroke and are essentially analogous to unstable angina. Some 10% of TIAs convert to full strokes within 90 days, but growing evidence suggests appropriate interventions can decrease this risk to 3%.²

Unfortunately, the symptoms of TIA have usually resolved by the time patients arrive at the hospital, which makes them challenging to diagnose. This article provides a summary of how to diagnose TIA accurately, using a focused history informed by cerebrovascular localization; how to triage, evaluate, and risk stratify patients; and how to implement preventative strategies.

Review of the Data

Classically, TIAs are defined as lasting less than 24 hours; however, 24 hours is an arbitrary number, and most TIAs last less than one hour.¹ Furthermore, this definition has evolved with advances in neuroimaging that reveal that up to 50% of classically defined TIAs have evidence of infarct on MRI.¹ There is no absolute temporal cut-off after which infarct is always seen on MRI, but longer duration of symptoms correlates with a higher likelihood of infarct. To reconcile these observations, a recently proposed definition stipulates that a true TIA lasts no more than one hour and does not show evidence of infarct on MRI.³

The causes of TIA are identical to those for ischemic stroke. Cerebral ischemia can result from an embolus, arterial thrombosis, or hypoperfusion due to arterial stenosis. Emboli can be cardiac, most commonly due to AF, or non-cardiac, stemming from a ruptured atherosclerotic plaque in the aortic arch, the carotid or vertebral artery, or an intracranial vessel. Atherosclerotic disease in the carotid arteries or intracranial vessels can also lead to thrombosis and occlusion or flow-related TIAs as a result of severe stenosis.

Risk factors for TIA mirror those for heart disease. Non-modifiable risk factors include older age, black race, male sex, and family history of stroke. Modifiable factors include hypertension, hyperlipidemia, tobacco smoking, diabetes, and AF.⁴

Most of the time, patients’ symptoms will have resolved by the time they are evaluated by a physician. Therefore, the diagnosis of TIA relies almost exclusively on the patient history. Eliciting a good history helps physicians determine whether the episode of transient neurologic dysfunction was caused by cerebral ischemia, as opposed to another mechanism, such as migraine or seizure. This calls for a basic understanding of cerebrovascular anatomy (see Table 1).

Types of Ischemia

Anterior cerebral artery ischemia causes contralateral leg weakness because it supplies the medial frontal and parietal lobes, where the legs in the sensorimotor homunculus are represented. Middle cerebral artery (MCA) ischemia causes contralateral face and arm weakness out of proportion to leg weakness. Ischemia in Broca’s area of the brain, which is supplied by the left MCA, may also cause expressive aphasia. Transient monocular blindness is a TIA of the retina due to atheroemboli originating from the internal carotid artery. Vertebrobasilar TIA is less common than anterior circulation TIA and manifests with brainstem symptoms that include diplopia, dysarthria, dysphagia, vertigo, gait imbalance, and weakness. In general, language and motor symptoms are more specific for cerebral ischemia and therefore more worrisome for TIA than sensory symptoms.⁵

 

Once a clinical diagnosis of TIA is made, an ABCD2 score (age, blood pressure, clinical features, duration of TIA, presence of diabetes) can be used to predict the short-term risk of subsequent stroke (see Table 2).^6,7 A general rule of thumb is to admit patients who present within 72 hours of the event and have an ABCD2 score of three or higher for observation, work-up, and initiation of secondary prevention.¹

Although only a small percentage of patients with TIA will have a stroke during the period of observation in the hospital, this approach may be cost effective based on the assumption that hospitalized patients are more likely to receive intravenous tissue plasminogen activator.⁸ The decision should also be guided by clinical judgment. It is reasonable to admit a patient whose diagnostic workup cannot be rapidly completed.¹

The workup for TIA includes routine labs, EKG with cardiac monitoring, and brain imaging. Labs are useful to evaluate for other mimics of TIA such as hyponatremia and glucose abnormalities. In addition, risk factors such as hyperlipidemia and diabetes should be evaluated with fasting lipid panel and blood glucose. The purpose of EKG and telemetry is to identify MI and capture paroxysmal AF. The goal of imaging is to ascertain the presence of vascular disease and to exclude a non-ischemic etiology. While less likely to cause transient neurologic symptoms, a hemorrhagic event must be ruled out, as it would trigger a different management pathway.

Imaging for TIA

There are two primary modes of brain imaging: computed tomography (CT) and MRI. Most patients who are suspected to have had a TIA undergo CT scan, and an infarct is seen about 20% of the time.¹ The presence of an infarct usually correlates with the duration of symptoms and has prognostic value. In one study, a new infarct was associated with four times higher risk of stroke in the subsequent 90 days.⁹ Diffusion-weighted imaging, an MR-based technique, is the preferred modality when it is available because of its higher sensitivity and specificity for identifying acute lesions.¹ In an international and multicenter study, incorporating imaging data increased the discriminatory power of stroke prediction.¹⁰

Extracranial imaging is mandatory to rule out carotid stenosis as a potential etiology of TIA. The least invasive modality is ultrasound, which can detect carotid stenosis with a sensitivity and specificity approaching 80%.¹ While both the intra- and extracranial vasculature can be concurrently assessed using MR- or CT-angiography (CTA), this is not usually necessary in the acute setting, because only detecting carotid stenosis will result in a management change.¹

Carotid endarterectomy is standard for symptomatic patients with greater than 70% stenosis and is a consideration for symptomatic patients with greater than 50% stenosis if it is the most probable explanation for the ischemic event.¹¹ Despite a comprehensive workup, about 50% of TIA cases remain cryptogenic.¹² In some of these patients, AF can be detected using extended ambulatory cardiac monitoring.¹²

The goal of admitting high-risk patients is to expedite workup and initiate therapy. Two studies have shown that immediate initiation of preventative treatment significantly reduces the risk of stroke by as much as 80%.^13,14 Unless there is a specific indication for anticoagulation, all TIA patients should be started on an antiplatelet agent such as aspirin or clopidogrel. A large randomized trial conducted in China and published in 2013 demonstrated that dual antiplatelet therapy with aspirin and clopidogrel for 21 days, followed by clopidogrel monotherapy, reduced the risk of stroke compared to aspirin monotherapy. An international multicenter trial designed to test the efficacy of short-term dual antiplatelet therapy is ongoing, and if the benefit of this approach is confirmed, this will likely become the standard of care. Evidence-based indications for anticoagulation after TIA are restricted to AF and mural thrombus in the setting of recent MI. Patients with implanted mechanical devices, including left ventricular assist devices and metal heart valves, should also receive anticoagulation.¹⁵

 

Risk factors should also be targeted in every case. Hypertension should be treated with a goal of lower than 140/90 mm Hg (or 130/80 mm Hg in diabetics and those with renal disease). Studies have shown that patients who are discharged with a blood pressure lower than 140/90 mm Hg are more likely to maintain this blood pressure at one-year follow-up.¹⁶ The choice of medication is less well studied, but drugs that act on the renin-angiotensin-aldosterone system and thiazides are generally preferred.¹⁵ Treatment with a statin is recommended after cerebrovascular ischemic events, with a goal LDL under 100. This reduces risk of secondary stroke by about 20%.¹⁷

At discharge, it is also important to counsel patients on their role in preventing strokes. As with many diseases, making lifestyle changes is key to stroke prevention. Encourage smoking cessation and an increase in physical activity, and discourage heavy alcohol use. The association between smoking and the risk for first stroke is well established. Moderate to high-intensity exercise can reduce secondary stroke risk by as much as 50%¹⁸ (see Table 3). While light alcohol consumption can be protective against strokes, heavy use is strongly discouraged. Emerging data suggest obstructive sleep apnea (OSA) may be another modifiable risk factor for stroke and TIA, so screening for potential OSA and referral may be needed.¹⁵

Back to the Case

When Mr. G arrived at the ED, his symptoms had resolved. Based on the history of expressive aphasia and right-sided weakness, he most likely had a TIA in the left MCA territory. Hemorrhage was ruled out with a non-contrast head CT. His pacemaker precluded obtaining an MRI. CTA revealed diffuse atherosclerotic disease without evidence of carotid stenosis. His ABCD2 score was six given his age, blood pressure, weakness, and symptom duration, and he was admitted for an expedited workup. His sodium and glucose were within normal limits. His hemoglobin A1c was 6.5%, his LDL was 120, and his international normalized ratio (INR) was therapeutic at 2.1. His TIA may have been due to AF, despite a therapeutic INR, because warfarin does not fully eliminate the stroke risk. It might also have been caused by intracranial atherosclerosis.

Two days later, the patient was discharged on atorvastatin at 80 mg, and his lisinopril was increased for blood pressure control. For his age group, A1c of 6.5% was acceptable, and he was not initiated on glycemic control.

Bottom Line

TIAs are diagnosed based on patient history. Urgent initiation of secondary prevention is important to reduce the short-term risk of stroke and should be implemented by the time of discharge from the hospital.

---

Dr. Zeng is a hospitalist in the department of internal medicine at Vanderbilt University Medical Center in Nashville, and Dr. Douglas is associate professor in the department of neurology at the University of California at San Francisco.

 

References

1. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009;40(6):2276-2293.
2. Sundararajan V, Thrift AG, Phan TG, Choi PM, Clissold B, Srikanth VK. Trends over time in the risk of stroke after an incident transient ischemic attack. Stroke. 2014;45(11):3214-3218.
3. Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack–proposal for a new definition. N Engl J Med. 2002;347(21):1713-1716.
4. Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin. 2008;26(4):871-895, vii.
5. Johnston SC, Sidney S, Bernstein AL, Gress DR. A comparison of risk factors for recurrent TIA and stroke in patients diagnosed with TIA. Neurology. 2003;60(2):280-285.
6. Tsivgoulis G, Stamboulis E, Sharma VK, et al. Multicenter external validation of the ABCD2 score in triaging TIA patients. Neurology. 2010;74(17):1351-1357.
7. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369(9558):283-292.
8. Nguyen-Huynh MN, Johnston SC. Is hospitalization after TIA cost-effective on the basis of treatment with tPA? Neurology. 2005;65(11):1799-1801.
9. Douglas VC, Johnston CM, Elkins J, Sidney S, Gress DR, Johnston SC. Head computed tomography findings predict short-term stroke risk after transient ischemic attack. Stroke. 2003;34(12):2894-2898.
10. Giles MF, Albers GW, Amarenco P, et al. Addition of brain infarction to the ABCD2 Score (ABCD2I): a collaborative analysis of unpublished data on 4574 patients. Stroke. 2010;41(9):1907-1913.
11. Lanzino G, Rabinstein AA, Brown RD Jr. Treatment of carotid artery stenosis: medical therapy, surgery, or stenting? Mayo Clin Proc. 2009;84(4):362-387; quiz 367-368.
12. Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370(26):2467-2477.
13. Lavallée PC, Meseguer E, Abboud H, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007;6(11):953-960.
14. Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007;370(9596):1432-1442.
15. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-2236.
16. Roumie CL, Zillich AJ, Bravata DM, et al. Hypertension treatment intensification among stroke survivors with uncontrolled blood pressure. Stroke. 2015;46(2):465-470.
17. Amarenco P, Bogousslavsky J, Callahan A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559.
18. Lennon O, Galvin R, Smith K, Doody C, Blake C. Lifestyle interventions for secondary disease prevention in stroke and transient ischaemic attack: a systematic review. Eur J Prev Cardiol. 2014;21(8):1026-1039.

Case

Mr. G is an 80-year-old man with a pacemaker, peripheral artery disease, atrial fibrillation (AF) on warfarin, and tachy-brady syndrome. He presented after experiencing episodes in which he was unable to speak and had weakness on his right side. He had a normal neurological exam upon arrival to the ED, and his blood pressure was 160/80 mm Hg.

Overview

Transient ischemic attacks (TIAs) are brief interruptions in brain perfusion that do not result in permanent neurologic damage. Up to half a million TIAs occur each year in the U.S., and they account for one third of acute cerebrovascular disease.1 While the term suggests that TIAs are benign, they are in fact an important warning sign of impending stroke and are essentially analogous to unstable angina. Some 10% of TIAs convert to full strokes within 90 days, but growing evidence suggests appropriate interventions can decrease this risk to 3%.²

Unfortunately, the symptoms of TIA have usually resolved by the time patients arrive at the hospital, which makes them challenging to diagnose. This article provides a summary of how to diagnose TIA accurately, using a focused history informed by cerebrovascular localization; how to triage, evaluate, and risk stratify patients; and how to implement preventative strategies.

Review of the Data

Classically, TIAs are defined as lasting less than 24 hours; however, 24 hours is an arbitrary number, and most TIAs last less than one hour.¹ Furthermore, this definition has evolved with advances in neuroimaging that reveal that up to 50% of classically defined TIAs have evidence of infarct on MRI.¹ There is no absolute temporal cut-off after which infarct is always seen on MRI, but longer duration of symptoms correlates with a higher likelihood of infarct. To reconcile these observations, a recently proposed definition stipulates that a true TIA lasts no more than one hour and does not show evidence of infarct on MRI.³

The causes of TIA are identical to those for ischemic stroke. Cerebral ischemia can result from an embolus, arterial thrombosis, or hypoperfusion due to arterial stenosis. Emboli can be cardiac, most commonly due to AF, or non-cardiac, stemming from a ruptured atherosclerotic plaque in the aortic arch, the carotid or vertebral artery, or an intracranial vessel. Atherosclerotic disease in the carotid arteries or intracranial vessels can also lead to thrombosis and occlusion or flow-related TIAs as a result of severe stenosis.

Risk factors for TIA mirror those for heart disease. Non-modifiable risk factors include older age, black race, male sex, and family history of stroke. Modifiable factors include hypertension, hyperlipidemia, tobacco smoking, diabetes, and AF.⁴

Most of the time, patients’ symptoms will have resolved by the time they are evaluated by a physician. Therefore, the diagnosis of TIA relies almost exclusively on the patient history. Eliciting a good history helps physicians determine whether the episode of transient neurologic dysfunction was caused by cerebral ischemia, as opposed to another mechanism, such as migraine or seizure. This calls for a basic understanding of cerebrovascular anatomy (see Table 1).

Types of Ischemia

Anterior cerebral artery ischemia causes contralateral leg weakness because it supplies the medial frontal and parietal lobes, where the legs in the sensorimotor homunculus are represented. Middle cerebral artery (MCA) ischemia causes contralateral face and arm weakness out of proportion to leg weakness. Ischemia in Broca’s area of the brain, which is supplied by the left MCA, may also cause expressive aphasia. Transient monocular blindness is a TIA of the retina due to atheroemboli originating from the internal carotid artery. Vertebrobasilar TIA is less common than anterior circulation TIA and manifests with brainstem symptoms that include diplopia, dysarthria, dysphagia, vertigo, gait imbalance, and weakness. In general, language and motor symptoms are more specific for cerebral ischemia and therefore more worrisome for TIA than sensory symptoms.⁵

 

Once a clinical diagnosis of TIA is made, an ABCD2 score (age, blood pressure, clinical features, duration of TIA, presence of diabetes) can be used to predict the short-term risk of subsequent stroke (see Table 2).^6,7 A general rule of thumb is to admit patients who present within 72 hours of the event and have an ABCD2 score of three or higher for observation, work-up, and initiation of secondary prevention.¹

Although only a small percentage of patients with TIA will have a stroke during the period of observation in the hospital, this approach may be cost effective based on the assumption that hospitalized patients are more likely to receive intravenous tissue plasminogen activator.⁸ The decision should also be guided by clinical judgment. It is reasonable to admit a patient whose diagnostic workup cannot be rapidly completed.¹

The workup for TIA includes routine labs, EKG with cardiac monitoring, and brain imaging. Labs are useful to evaluate for other mimics of TIA such as hyponatremia and glucose abnormalities. In addition, risk factors such as hyperlipidemia and diabetes should be evaluated with fasting lipid panel and blood glucose. The purpose of EKG and telemetry is to identify MI and capture paroxysmal AF. The goal of imaging is to ascertain the presence of vascular disease and to exclude a non-ischemic etiology. While less likely to cause transient neurologic symptoms, a hemorrhagic event must be ruled out, as it would trigger a different management pathway.

Imaging for TIA

There are two primary modes of brain imaging: computed tomography (CT) and MRI. Most patients who are suspected to have had a TIA undergo CT scan, and an infarct is seen about 20% of the time.¹ The presence of an infarct usually correlates with the duration of symptoms and has prognostic value. In one study, a new infarct was associated with four times higher risk of stroke in the subsequent 90 days.⁹ Diffusion-weighted imaging, an MR-based technique, is the preferred modality when it is available because of its higher sensitivity and specificity for identifying acute lesions.¹ In an international and multicenter study, incorporating imaging data increased the discriminatory power of stroke prediction.¹⁰

Extracranial imaging is mandatory to rule out carotid stenosis as a potential etiology of TIA. The least invasive modality is ultrasound, which can detect carotid stenosis with a sensitivity and specificity approaching 80%.¹ While both the intra- and extracranial vasculature can be concurrently assessed using MR- or CT-angiography (CTA), this is not usually necessary in the acute setting, because only detecting carotid stenosis will result in a management change.¹

Carotid endarterectomy is standard for symptomatic patients with greater than 70% stenosis and is a consideration for symptomatic patients with greater than 50% stenosis if it is the most probable explanation for the ischemic event.¹¹ Despite a comprehensive workup, about 50% of TIA cases remain cryptogenic.¹² In some of these patients, AF can be detected using extended ambulatory cardiac monitoring.¹²

The goal of admitting high-risk patients is to expedite workup and initiate therapy. Two studies have shown that immediate initiation of preventative treatment significantly reduces the risk of stroke by as much as 80%.^13,14 Unless there is a specific indication for anticoagulation, all TIA patients should be started on an antiplatelet agent such as aspirin or clopidogrel. A large randomized trial conducted in China and published in 2013 demonstrated that dual antiplatelet therapy with aspirin and clopidogrel for 21 days, followed by clopidogrel monotherapy, reduced the risk of stroke compared to aspirin monotherapy. An international multicenter trial designed to test the efficacy of short-term dual antiplatelet therapy is ongoing, and if the benefit of this approach is confirmed, this will likely become the standard of care. Evidence-based indications for anticoagulation after TIA are restricted to AF and mural thrombus in the setting of recent MI. Patients with implanted mechanical devices, including left ventricular assist devices and metal heart valves, should also receive anticoagulation.¹⁵

 

Risk factors should also be targeted in every case. Hypertension should be treated with a goal of lower than 140/90 mm Hg (or 130/80 mm Hg in diabetics and those with renal disease). Studies have shown that patients who are discharged with a blood pressure lower than 140/90 mm Hg are more likely to maintain this blood pressure at one-year follow-up.¹⁶ The choice of medication is less well studied, but drugs that act on the renin-angiotensin-aldosterone system and thiazides are generally preferred.¹⁵ Treatment with a statin is recommended after cerebrovascular ischemic events, with a goal LDL under 100. This reduces risk of secondary stroke by about 20%.¹⁷

At discharge, it is also important to counsel patients on their role in preventing strokes. As with many diseases, making lifestyle changes is key to stroke prevention. Encourage smoking cessation and an increase in physical activity, and discourage heavy alcohol use. The association between smoking and the risk for first stroke is well established. Moderate to high-intensity exercise can reduce secondary stroke risk by as much as 50%¹⁸ (see Table 3). While light alcohol consumption can be protective against strokes, heavy use is strongly discouraged. Emerging data suggest obstructive sleep apnea (OSA) may be another modifiable risk factor for stroke and TIA, so screening for potential OSA and referral may be needed.¹⁵

Back to the Case

When Mr. G arrived at the ED, his symptoms had resolved. Based on the history of expressive aphasia and right-sided weakness, he most likely had a TIA in the left MCA territory. Hemorrhage was ruled out with a non-contrast head CT. His pacemaker precluded obtaining an MRI. CTA revealed diffuse atherosclerotic disease without evidence of carotid stenosis. His ABCD2 score was six given his age, blood pressure, weakness, and symptom duration, and he was admitted for an expedited workup. His sodium and glucose were within normal limits. His hemoglobin A1c was 6.5%, his LDL was 120, and his international normalized ratio (INR) was therapeutic at 2.1. His TIA may have been due to AF, despite a therapeutic INR, because warfarin does not fully eliminate the stroke risk. It might also have been caused by intracranial atherosclerosis.

Two days later, the patient was discharged on atorvastatin at 80 mg, and his lisinopril was increased for blood pressure control. For his age group, A1c of 6.5% was acceptable, and he was not initiated on glycemic control.

Bottom Line

TIAs are diagnosed based on patient history. Urgent initiation of secondary prevention is important to reduce the short-term risk of stroke and should be implemented by the time of discharge from the hospital.

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Dr. Zeng is a hospitalist in the department of internal medicine at Vanderbilt University Medical Center in Nashville, and Dr. Douglas is associate professor in the department of neurology at the University of California at San Francisco.

 

References

1. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009;40(6):2276-2293.
2. Sundararajan V, Thrift AG, Phan TG, Choi PM, Clissold B, Srikanth VK. Trends over time in the risk of stroke after an incident transient ischemic attack. Stroke. 2014;45(11):3214-3218.
3. Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack–proposal for a new definition. N Engl J Med. 2002;347(21):1713-1716.
4. Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin. 2008;26(4):871-895, vii.
5. Johnston SC, Sidney S, Bernstein AL, Gress DR. A comparison of risk factors for recurrent TIA and stroke in patients diagnosed with TIA. Neurology. 2003;60(2):280-285.
6. Tsivgoulis G, Stamboulis E, Sharma VK, et al. Multicenter external validation of the ABCD2 score in triaging TIA patients. Neurology. 2010;74(17):1351-1357.
7. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369(9558):283-292.
8. Nguyen-Huynh MN, Johnston SC. Is hospitalization after TIA cost-effective on the basis of treatment with tPA? Neurology. 2005;65(11):1799-1801.
9. Douglas VC, Johnston CM, Elkins J, Sidney S, Gress DR, Johnston SC. Head computed tomography findings predict short-term stroke risk after transient ischemic attack. Stroke. 2003;34(12):2894-2898.
10. Giles MF, Albers GW, Amarenco P, et al. Addition of brain infarction to the ABCD2 Score (ABCD2I): a collaborative analysis of unpublished data on 4574 patients. Stroke. 2010;41(9):1907-1913.
11. Lanzino G, Rabinstein AA, Brown RD Jr. Treatment of carotid artery stenosis: medical therapy, surgery, or stenting? Mayo Clin Proc. 2009;84(4):362-387; quiz 367-368.
12. Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370(26):2467-2477.
13. Lavallée PC, Meseguer E, Abboud H, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007;6(11):953-960.
14. Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007;370(9596):1432-1442.
15. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-2236.
16. Roumie CL, Zillich AJ, Bravata DM, et al. Hypertension treatment intensification among stroke survivors with uncontrolled blood pressure. Stroke. 2015;46(2):465-470.
17. Amarenco P, Bogousslavsky J, Callahan A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559.
18. Lennon O, Galvin R, Smith K, Doody C, Blake C. Lifestyle interventions for secondary disease prevention in stroke and transient ischaemic attack: a systematic review. Eur J Prev Cardiol. 2014;21(8):1026-1039.

Clinical question: Should steroids be used as adjunctive therapy for patients with community-acquired pneumonia?

Bottom line: Moderate-quality to high-quality evidence suggests that steroids, when added to antibiotics and usual care, can improve outcomes in the treatment of community-acquired pneumonia (CAP). Benefits include reduced hospital length of stay, decreased time to clinical stability, and lower rates of mechanical ventilation and acute respiratory distress syndrome. Steroids may also play a role in preventing deaths, especially in patients with severe CAP; however, the certainty of this evidence is not as clear. Given varying treatment regimens used in the individual studies, the appropriate steroid formulation, dose, and duration of steroids cannot be elucidated from the current set of data. (LOE = 1a)

Reference: Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med. 2015;163(7):519-528.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These authors searched MEDLINE, EMBASE, and the Cochrane Register to find randomized controlled trials that compared the use of steroids with placebo in adults with CAP. Two reviewers independently evaluated studies for eligibility, extracted data, and assessed the included studies for risk of bias. Five of the 13 included studies, whose population made up 70% of the total sample population, had low risk of bias. The treatment groups in the individual studies received different steroid preparations, routes of administration, dosages, and duration of treatment. All groups otherwise received antibiotics and usual care for CAP.

High-quality evidence showed that the use of steroids decreased hospital length of stay by 1 day (3 studies: mean difference: -1.0 day; 95% CI -1.79 to -0.21 days) and decreased time to clinical stability by 1.22 days (5 studies, mean difference: -1.22 days; -2.08 to -0.35 days). Moderate-quality evidence showed that the use of steroids decreased the need for mechanical ventilation (5 studies: relative risk [RR] = 0.45; 0.26-0.79) and the incidence of acute respiratory distress syndrome (4 studies: RR = 0.24; 0.10-0.56).

Finally, data from the 12 trials that assessed all-cause mortality revealed a trend toward decreased risk of death in the steroid group. The difference between the two groups for this end point became statistically significant when only the trials that met the criteria for severe pneumonia were included (6 studies: RR = 0.39; 0.20-0.77). Although steroid use, not surprisingly, increased the risk of significant hyperglycemia (6 studies: RR = 1.49;1.01-2.19), there were no differences detected in the rates of gastrointestinal bleeds, severe neuropsychiatric complications, or rehospitalizations.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Should steroids be used as adjunctive therapy for patients with community-acquired pneumonia?

Bottom line: Moderate-quality to high-quality evidence suggests that steroids, when added to antibiotics and usual care, can improve outcomes in the treatment of community-acquired pneumonia (CAP). Benefits include reduced hospital length of stay, decreased time to clinical stability, and lower rates of mechanical ventilation and acute respiratory distress syndrome. Steroids may also play a role in preventing deaths, especially in patients with severe CAP; however, the certainty of this evidence is not as clear. Given varying treatment regimens used in the individual studies, the appropriate steroid formulation, dose, and duration of steroids cannot be elucidated from the current set of data. (LOE = 1a)

Reference: Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med. 2015;163(7):519-528.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These authors searched MEDLINE, EMBASE, and the Cochrane Register to find randomized controlled trials that compared the use of steroids with placebo in adults with CAP. Two reviewers independently evaluated studies for eligibility, extracted data, and assessed the included studies for risk of bias. Five of the 13 included studies, whose population made up 70% of the total sample population, had low risk of bias. The treatment groups in the individual studies received different steroid preparations, routes of administration, dosages, and duration of treatment. All groups otherwise received antibiotics and usual care for CAP.

High-quality evidence showed that the use of steroids decreased hospital length of stay by 1 day (3 studies: mean difference: -1.0 day; 95% CI -1.79 to -0.21 days) and decreased time to clinical stability by 1.22 days (5 studies, mean difference: -1.22 days; -2.08 to -0.35 days). Moderate-quality evidence showed that the use of steroids decreased the need for mechanical ventilation (5 studies: relative risk [RR] = 0.45; 0.26-0.79) and the incidence of acute respiratory distress syndrome (4 studies: RR = 0.24; 0.10-0.56).

Finally, data from the 12 trials that assessed all-cause mortality revealed a trend toward decreased risk of death in the steroid group. The difference between the two groups for this end point became statistically significant when only the trials that met the criteria for severe pneumonia were included (6 studies: RR = 0.39; 0.20-0.77). Although steroid use, not surprisingly, increased the risk of significant hyperglycemia (6 studies: RR = 1.49;1.01-2.19), there were no differences detected in the rates of gastrointestinal bleeds, severe neuropsychiatric complications, or rehospitalizations.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Should steroids be used as adjunctive therapy for patients with community-acquired pneumonia?

Bottom line: Moderate-quality to high-quality evidence suggests that steroids, when added to antibiotics and usual care, can improve outcomes in the treatment of community-acquired pneumonia (CAP). Benefits include reduced hospital length of stay, decreased time to clinical stability, and lower rates of mechanical ventilation and acute respiratory distress syndrome. Steroids may also play a role in preventing deaths, especially in patients with severe CAP; however, the certainty of this evidence is not as clear. Given varying treatment regimens used in the individual studies, the appropriate steroid formulation, dose, and duration of steroids cannot be elucidated from the current set of data. (LOE = 1a)

Reference: Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med. 2015;163(7):519-528.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These authors searched MEDLINE, EMBASE, and the Cochrane Register to find randomized controlled trials that compared the use of steroids with placebo in adults with CAP. Two reviewers independently evaluated studies for eligibility, extracted data, and assessed the included studies for risk of bias. Five of the 13 included studies, whose population made up 70% of the total sample population, had low risk of bias. The treatment groups in the individual studies received different steroid preparations, routes of administration, dosages, and duration of treatment. All groups otherwise received antibiotics and usual care for CAP.

High-quality evidence showed that the use of steroids decreased hospital length of stay by 1 day (3 studies: mean difference: -1.0 day; 95% CI -1.79 to -0.21 days) and decreased time to clinical stability by 1.22 days (5 studies, mean difference: -1.22 days; -2.08 to -0.35 days). Moderate-quality evidence showed that the use of steroids decreased the need for mechanical ventilation (5 studies: relative risk [RR] = 0.45; 0.26-0.79) and the incidence of acute respiratory distress syndrome (4 studies: RR = 0.24; 0.10-0.56).

Finally, data from the 12 trials that assessed all-cause mortality revealed a trend toward decreased risk of death in the steroid group. The difference between the two groups for this end point became statistically significant when only the trials that met the criteria for severe pneumonia were included (6 studies: RR = 0.39; 0.20-0.77). Although steroid use, not surprisingly, increased the risk of significant hyperglycemia (6 studies: RR = 1.49;1.01-2.19), there were no differences detected in the rates of gastrointestinal bleeds, severe neuropsychiatric complications, or rehospitalizations.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular thrombectomy improve clinical outcomes in patients presenting with acute ischemic stroke?

Bottom line: High-quality evidence shows that endovascular therapy using mechanical thrombectomy for the treatment of acute ischemic stroke leads to improved functional outcomes as compared with standard medical therapy with intravenous tissue plasminogen activator (tPA). You would have to treat 8 patients with endovascular therapy to achieve functional independence for 1 patient. (LOE = 1a)

Reference: Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA 2015;314(17):1832–1843.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including MEDLINE, EMBASE, Google Scholar, and the Cochrane Library to find randomized clinical trials that compared endovascular mechanical thrombectomy with tPA for the treatment of acute ischemic stroke. Three reviewers independently evaluated the studies for eligibility, extracted data from the included studies, and assessed study quality using the Cochrane Collaboration's tool for risk of bias. Ultimately, 8 studies with a total of 2423 patients were included in the review. Most studies used a time window of 6 hours from stroke onset for time to endovascular therapy. The primary outcome was the modified Rankin Scale (mRS) score, which measures the degree of functional disability (a scale of 0 to 6, where 0 = no symptoms, 1 = symptoms but no disability, 5 = severe disability, and 6 = death).

Endovascular thrombectomy led to reduced disability at 90 days (odds ratio = 1.56; 95% CI 1.14-2.13; P = .005). Furthermore, those who received endovascular thrombectomy were more likely to be functionally independent (mRS score of 0, 1, or 2) than those who received tPA (45% vs 32%; P = .005; number needed to treat = 8). There were no significant differences detected in mortality, symptomatic intracranial bleeds, or in-hospital medical complications. Given the high degree of heterogeneity noted in the primary end point, subgroup and sensitivity analyses were performed that showed better functional outcomes in patients with confirmed proximal arterial occlusion, those who received combined tPA and endovascular interventions, and those who had the newer retrievable stent devices used for thrombectomy. More recent studies, as compared with earlier studies, were also more likely to favor endovascular thrombectomy.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular thrombectomy improve clinical outcomes in patients presenting with acute ischemic stroke?

Bottom line: High-quality evidence shows that endovascular therapy using mechanical thrombectomy for the treatment of acute ischemic stroke leads to improved functional outcomes as compared with standard medical therapy with intravenous tissue plasminogen activator (tPA). You would have to treat 8 patients with endovascular therapy to achieve functional independence for 1 patient. (LOE = 1a)

Reference: Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA 2015;314(17):1832–1843.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including MEDLINE, EMBASE, Google Scholar, and the Cochrane Library to find randomized clinical trials that compared endovascular mechanical thrombectomy with tPA for the treatment of acute ischemic stroke. Three reviewers independently evaluated the studies for eligibility, extracted data from the included studies, and assessed study quality using the Cochrane Collaboration's tool for risk of bias. Ultimately, 8 studies with a total of 2423 patients were included in the review. Most studies used a time window of 6 hours from stroke onset for time to endovascular therapy. The primary outcome was the modified Rankin Scale (mRS) score, which measures the degree of functional disability (a scale of 0 to 6, where 0 = no symptoms, 1 = symptoms but no disability, 5 = severe disability, and 6 = death).

Endovascular thrombectomy led to reduced disability at 90 days (odds ratio = 1.56; 95% CI 1.14-2.13; P = .005). Furthermore, those who received endovascular thrombectomy were more likely to be functionally independent (mRS score of 0, 1, or 2) than those who received tPA (45% vs 32%; P = .005; number needed to treat = 8). There were no significant differences detected in mortality, symptomatic intracranial bleeds, or in-hospital medical complications. Given the high degree of heterogeneity noted in the primary end point, subgroup and sensitivity analyses were performed that showed better functional outcomes in patients with confirmed proximal arterial occlusion, those who received combined tPA and endovascular interventions, and those who had the newer retrievable stent devices used for thrombectomy. More recent studies, as compared with earlier studies, were also more likely to favor endovascular thrombectomy.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular thrombectomy improve clinical outcomes in patients presenting with acute ischemic stroke?

Bottom line: High-quality evidence shows that endovascular therapy using mechanical thrombectomy for the treatment of acute ischemic stroke leads to improved functional outcomes as compared with standard medical therapy with intravenous tissue plasminogen activator (tPA). You would have to treat 8 patients with endovascular therapy to achieve functional independence for 1 patient. (LOE = 1a)

Reference: Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA 2015;314(17):1832–1843.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including MEDLINE, EMBASE, Google Scholar, and the Cochrane Library to find randomized clinical trials that compared endovascular mechanical thrombectomy with tPA for the treatment of acute ischemic stroke. Three reviewers independently evaluated the studies for eligibility, extracted data from the included studies, and assessed study quality using the Cochrane Collaboration's tool for risk of bias. Ultimately, 8 studies with a total of 2423 patients were included in the review. Most studies used a time window of 6 hours from stroke onset for time to endovascular therapy. The primary outcome was the modified Rankin Scale (mRS) score, which measures the degree of functional disability (a scale of 0 to 6, where 0 = no symptoms, 1 = symptoms but no disability, 5 = severe disability, and 6 = death).

Endovascular thrombectomy led to reduced disability at 90 days (odds ratio = 1.56; 95% CI 1.14-2.13; P = .005). Furthermore, those who received endovascular thrombectomy were more likely to be functionally independent (mRS score of 0, 1, or 2) than those who received tPA (45% vs 32%; P = .005; number needed to treat = 8). There were no significant differences detected in mortality, symptomatic intracranial bleeds, or in-hospital medical complications. Given the high degree of heterogeneity noted in the primary end point, subgroup and sensitivity analyses were performed that showed better functional outcomes in patients with confirmed proximal arterial occlusion, those who received combined tPA and endovascular interventions, and those who had the newer retrievable stent devices used for thrombectomy. More recent studies, as compared with earlier studies, were also more likely to favor endovascular thrombectomy.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) is a new resource designed to help clinicians select the safest and most appropriate peripherally inserted central catheter (PICC) for individual patients.

“How do you decide which catheter is best for your patient? Until now there wasn’t a guide bringing together all of the best available evidence,” says the guide’s lead author Vineet Chopra, MD, MSc, FHM, a hospitalist and assistant professor of medicine at the University of Michigan in Ann Arbor.

“These are among the most commonly performed procedures on any hospitalized patient, and yet, the least studied,” he adds. “We as hospitalists are the physicians who order most of these devices, especially PICCs.”

The guide includes algorithms and color-coded pocket cards to help physicians determine which PICC to choose. The cards can be freely downloaded and printed from the Improve PICC website at the University of Michigan.

The project to develop the guide brought together 15 leading international experts on catheters and their infections and complications, including the authors of existing guidelines, to brainstorm more than 600 clinical scenarios and best evidence-based practice for catheter use using the Rand/UCLA Appropriateness Method. “We also had a patient on the panel, which was important to the clinicians because this patient had actually used many of the devices being discussed,” Dr. Chopra explains.

The guidelines “have the potential to change the game for hospitalists,” Dr. Chopra adds. “There has never before been guidance on using IV devices in hospitalized medical patients, despite the fact that we use these devices every day. Now, for the first time, we not only have guidance but also a tool to benchmark the quality of care provided by doctors when it comes to venous access.”

The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) is a new resource designed to help clinicians select the safest and most appropriate peripherally inserted central catheter (PICC) for individual patients.

“How do you decide which catheter is best for your patient? Until now there wasn’t a guide bringing together all of the best available evidence,” says the guide’s lead author Vineet Chopra, MD, MSc, FHM, a hospitalist and assistant professor of medicine at the University of Michigan in Ann Arbor.

“These are among the most commonly performed procedures on any hospitalized patient, and yet, the least studied,” he adds. “We as hospitalists are the physicians who order most of these devices, especially PICCs.”

The guide includes algorithms and color-coded pocket cards to help physicians determine which PICC to choose. The cards can be freely downloaded and printed from the Improve PICC website at the University of Michigan.

The project to develop the guide brought together 15 leading international experts on catheters and their infections and complications, including the authors of existing guidelines, to brainstorm more than 600 clinical scenarios and best evidence-based practice for catheter use using the Rand/UCLA Appropriateness Method. “We also had a patient on the panel, which was important to the clinicians because this patient had actually used many of the devices being discussed,” Dr. Chopra explains.

The guidelines “have the potential to change the game for hospitalists,” Dr. Chopra adds. “There has never before been guidance on using IV devices in hospitalized medical patients, despite the fact that we use these devices every day. Now, for the first time, we not only have guidance but also a tool to benchmark the quality of care provided by doctors when it comes to venous access.”

The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) is a new resource designed to help clinicians select the safest and most appropriate peripherally inserted central catheter (PICC) for individual patients.

“How do you decide which catheter is best for your patient? Until now there wasn’t a guide bringing together all of the best available evidence,” says the guide’s lead author Vineet Chopra, MD, MSc, FHM, a hospitalist and assistant professor of medicine at the University of Michigan in Ann Arbor.

“These are among the most commonly performed procedures on any hospitalized patient, and yet, the least studied,” he adds. “We as hospitalists are the physicians who order most of these devices, especially PICCs.”

The guide includes algorithms and color-coded pocket cards to help physicians determine which PICC to choose. The cards can be freely downloaded and printed from the Improve PICC website at the University of Michigan.

The project to develop the guide brought together 15 leading international experts on catheters and their infections and complications, including the authors of existing guidelines, to brainstorm more than 600 clinical scenarios and best evidence-based practice for catheter use using the Rand/UCLA Appropriateness Method. “We also had a patient on the panel, which was important to the clinicians because this patient had actually used many of the devices being discussed,” Dr. Chopra explains.

The guidelines “have the potential to change the game for hospitalists,” Dr. Chopra adds. “There has never before been guidance on using IV devices in hospitalized medical patients, despite the fact that we use these devices every day. Now, for the first time, we not only have guidance but also a tool to benchmark the quality of care provided by doctors when it comes to venous access.”

In the latest report in its series on quality and patient safety in healthcare, the Institute of Medicine addresses the challenge of errors in medical diagnoses.

Authors of the IOM’s “Improving Diagnosis in Health Care” report cite problems in communication and limitations in electronic health records behind inaccurate and delayed diagnoses, concluding that the problem of diagnostic errors generally has not been adequately studied.¹

“This problem is significant and serious. Yet we don’t know for sure how often it occurs, how serious it is, or how much it costs,” said the IOM committee’s chair, John Ball, MD, of the American College of Physicians, in a prepared statement. The report concludes there is no easy fix for the problem of diagnostic errors, which are a leading cause of adverse events in hospitals and of malpractice lawsuits for hospitalists, but calls for a major reassessment of the diagnostic process.²

Hospitalist Mangla Gulati, MD, FACP, SFHM, assistant chief medical officer at the University of Maryland Medical Center in Baltimore, says hospitalists would be remiss if they failed to take a closer look at the IOM report. “Diagnostic error is something we haven’t much talked about in medicine,” Dr. Gulati says. “Part of the goal of this report is to actually include the patient in those conversations.” Patients who are rehospitalized, she says, may have been given an incorrect initial diagnosis that was never rectified, or there may have been a failure to communicate important information.

“How many tests do we order where results come back after a patient leaves the hospital?” asks Kedar Mate, MD, senior vice president at the Institute for Healthcare Improvement and a hospitalist at Weill Cornell Medicine in New York City. “How many in-hospital diagnoses are made without all of the available information from outside providers?”

One simple intervention hospitalists could do immediately, he says, is to start tracking all important tests ordered for patients on a board in the medical team’s meeting room, only removing them from the board when results have been checked and communicated to the patient and outpatient provider.

References

1. National Academies of Sciences, Engineering, and Medicine. Improving Diagnosis in Health Care. Washington, DC: The National Academies Press. 2015.
2. Saber Tehrani AS, Lee HW, Mathews SC, et al. 25-year summary of U.S. malpractice claims for diagnostic errors 1986–2010: An analysis from the National Practitioner Data Bank. BMJ Qual Saf. 2013 Aug; 22(8):672–680.

In the latest report in its series on quality and patient safety in healthcare, the Institute of Medicine addresses the challenge of errors in medical diagnoses.

Authors of the IOM’s “Improving Diagnosis in Health Care” report cite problems in communication and limitations in electronic health records behind inaccurate and delayed diagnoses, concluding that the problem of diagnostic errors generally has not been adequately studied.¹

“This problem is significant and serious. Yet we don’t know for sure how often it occurs, how serious it is, or how much it costs,” said the IOM committee’s chair, John Ball, MD, of the American College of Physicians, in a prepared statement. The report concludes there is no easy fix for the problem of diagnostic errors, which are a leading cause of adverse events in hospitals and of malpractice lawsuits for hospitalists, but calls for a major reassessment of the diagnostic process.²

Hospitalist Mangla Gulati, MD, FACP, SFHM, assistant chief medical officer at the University of Maryland Medical Center in Baltimore, says hospitalists would be remiss if they failed to take a closer look at the IOM report. “Diagnostic error is something we haven’t much talked about in medicine,” Dr. Gulati says. “Part of the goal of this report is to actually include the patient in those conversations.” Patients who are rehospitalized, she says, may have been given an incorrect initial diagnosis that was never rectified, or there may have been a failure to communicate important information.

“How many tests do we order where results come back after a patient leaves the hospital?” asks Kedar Mate, MD, senior vice president at the Institute for Healthcare Improvement and a hospitalist at Weill Cornell Medicine in New York City. “How many in-hospital diagnoses are made without all of the available information from outside providers?”

One simple intervention hospitalists could do immediately, he says, is to start tracking all important tests ordered for patients on a board in the medical team’s meeting room, only removing them from the board when results have been checked and communicated to the patient and outpatient provider.

References

1. National Academies of Sciences, Engineering, and Medicine. Improving Diagnosis in Health Care. Washington, DC: The National Academies Press. 2015.
2. Saber Tehrani AS, Lee HW, Mathews SC, et al. 25-year summary of U.S. malpractice claims for diagnostic errors 1986–2010: An analysis from the National Practitioner Data Bank. BMJ Qual Saf. 2013 Aug; 22(8):672–680.

In the latest report in its series on quality and patient safety in healthcare, the Institute of Medicine addresses the challenge of errors in medical diagnoses.

Authors of the IOM’s “Improving Diagnosis in Health Care” report cite problems in communication and limitations in electronic health records behind inaccurate and delayed diagnoses, concluding that the problem of diagnostic errors generally has not been adequately studied.¹

“This problem is significant and serious. Yet we don’t know for sure how often it occurs, how serious it is, or how much it costs,” said the IOM committee’s chair, John Ball, MD, of the American College of Physicians, in a prepared statement. The report concludes there is no easy fix for the problem of diagnostic errors, which are a leading cause of adverse events in hospitals and of malpractice lawsuits for hospitalists, but calls for a major reassessment of the diagnostic process.²

Hospitalist Mangla Gulati, MD, FACP, SFHM, assistant chief medical officer at the University of Maryland Medical Center in Baltimore, says hospitalists would be remiss if they failed to take a closer look at the IOM report. “Diagnostic error is something we haven’t much talked about in medicine,” Dr. Gulati says. “Part of the goal of this report is to actually include the patient in those conversations.” Patients who are rehospitalized, she says, may have been given an incorrect initial diagnosis that was never rectified, or there may have been a failure to communicate important information.

“How many tests do we order where results come back after a patient leaves the hospital?” asks Kedar Mate, MD, senior vice president at the Institute for Healthcare Improvement and a hospitalist at Weill Cornell Medicine in New York City. “How many in-hospital diagnoses are made without all of the available information from outside providers?”

One simple intervention hospitalists could do immediately, he says, is to start tracking all important tests ordered for patients on a board in the medical team’s meeting room, only removing them from the board when results have been checked and communicated to the patient and outpatient provider.

References

1. National Academies of Sciences, Engineering, and Medicine. Improving Diagnosis in Health Care. Washington, DC: The National Academies Press. 2015.
2. Saber Tehrani AS, Lee HW, Mathews SC, et al. 25-year summary of U.S. malpractice claims for diagnostic errors 1986–2010: An analysis from the National Practitioner Data Bank. BMJ Qual Saf. 2013 Aug; 22(8):672–680.