Ethan Cumbler, MD

Clinical question: What characteristics in patients with acute encephalitis portend a worse prognosis?

Background: Acute encephalitis is a serious neurologic disease with high levels of associated morbidity, mortality, and cost of care. Yet, little is known about the factors that affect the outcome of patients with encephalitis.

Study design: Retrospective chart review of all consecutive patients diagnosed with acute encephalitis.

Setting: Mayo Clinic, Rochester, Minn.

Synopsis: A retrospective chart review revealed 198 patients with encephalitis, grouped into viral, autoimmune, or unknown/other encephalitis categories, with mortality rates of 8%, 12%, and 5%, respectively. Researchers calculated a modified Rankin Scale score (mRS) on factors associated with good (mRS=0-2) or poor (mRS=3-6) outcome after one year. Factors associated with poor outcome included age 65 or older, immunocompromised state, coma, mechanical ventilation, and acute thrombocytopenia. Unlike some previous studies, MRI findings and seizure activity did not portend a poor outcome. For viral encephalitis, cerebrospinal fluid polymorphonuclear cell count was also strongly associated with poor outcome.

This is one of the first studies to evaluate functional outcome or distant follow-up; however, it has inherent biases related to the retrospective design, and the results are not necessarily generalizable to all hospitals; there might be an underlying referral bias, given the fact that one third of the patients were referred to the center for further evaluation.

This study does suggest aggressive treatment should be pursued, even in patients with severe presentation, given the possibility of favorable recovery.

Bottom line: Advanced age, immunocompromised state, coma, mechanical ventilation, and acute thrombocytopenia portend a worse outcome for patients with acute encephalitis.

Citation: Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology. 2015;84(4):359-366.

Clinical question: What characteristics in patients with acute encephalitis portend a worse prognosis?

Background: Acute encephalitis is a serious neurologic disease with high levels of associated morbidity, mortality, and cost of care. Yet, little is known about the factors that affect the outcome of patients with encephalitis.

Study design: Retrospective chart review of all consecutive patients diagnosed with acute encephalitis.

Setting: Mayo Clinic, Rochester, Minn.

Synopsis: A retrospective chart review revealed 198 patients with encephalitis, grouped into viral, autoimmune, or unknown/other encephalitis categories, with mortality rates of 8%, 12%, and 5%, respectively. Researchers calculated a modified Rankin Scale score (mRS) on factors associated with good (mRS=0-2) or poor (mRS=3-6) outcome after one year. Factors associated with poor outcome included age 65 or older, immunocompromised state, coma, mechanical ventilation, and acute thrombocytopenia. Unlike some previous studies, MRI findings and seizure activity did not portend a poor outcome. For viral encephalitis, cerebrospinal fluid polymorphonuclear cell count was also strongly associated with poor outcome.

This is one of the first studies to evaluate functional outcome or distant follow-up; however, it has inherent biases related to the retrospective design, and the results are not necessarily generalizable to all hospitals; there might be an underlying referral bias, given the fact that one third of the patients were referred to the center for further evaluation.

This study does suggest aggressive treatment should be pursued, even in patients with severe presentation, given the possibility of favorable recovery.

Bottom line: Advanced age, immunocompromised state, coma, mechanical ventilation, and acute thrombocytopenia portend a worse outcome for patients with acute encephalitis.

Citation: Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology. 2015;84(4):359-366.

Clinical question: What characteristics in patients with acute encephalitis portend a worse prognosis?

Background: Acute encephalitis is a serious neurologic disease with high levels of associated morbidity, mortality, and cost of care. Yet, little is known about the factors that affect the outcome of patients with encephalitis.

Study design: Retrospective chart review of all consecutive patients diagnosed with acute encephalitis.

Setting: Mayo Clinic, Rochester, Minn.

Synopsis: A retrospective chart review revealed 198 patients with encephalitis, grouped into viral, autoimmune, or unknown/other encephalitis categories, with mortality rates of 8%, 12%, and 5%, respectively. Researchers calculated a modified Rankin Scale score (mRS) on factors associated with good (mRS=0-2) or poor (mRS=3-6) outcome after one year. Factors associated with poor outcome included age 65 or older, immunocompromised state, coma, mechanical ventilation, and acute thrombocytopenia. Unlike some previous studies, MRI findings and seizure activity did not portend a poor outcome. For viral encephalitis, cerebrospinal fluid polymorphonuclear cell count was also strongly associated with poor outcome.

This is one of the first studies to evaluate functional outcome or distant follow-up; however, it has inherent biases related to the retrospective design, and the results are not necessarily generalizable to all hospitals; there might be an underlying referral bias, given the fact that one third of the patients were referred to the center for further evaluation.

This study does suggest aggressive treatment should be pursued, even in patients with severe presentation, given the possibility of favorable recovery.

Bottom line: Advanced age, immunocompromised state, coma, mechanical ventilation, and acute thrombocytopenia portend a worse outcome for patients with acute encephalitis.

Citation: Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology. 2015;84(4):359-366.

Clinical question: How does peri-operative hyperglycemia affect the risk of adverse events in diabetic patients compared to nondiabetic patients?

Background: Peri-operative hyperglycemia is associated with increased rates of infection, myocardial infarction, stroke, and death. Recent studies suggest that nondiabetics are more prone to hyperglycemia-related complications than diabetics. This study sought to analyze the effect and mechanism by which nondiabetics may be at increased risk for such complications.

Study Design: Retrospective cohort study.

Setting: Fifty-three hospitals in Washington.

Synopsis: Among 40,836 patients who underwent surgery, diabetics had a higher rate of peri-operative adverse events overall compared to nondiabetics (12% vs. 9%, P<0.001). Peri-operative hyperglycemia, defined as blood glucose 180 or greater, was also associated with an increased rate of adverse events. Ironically, this association was more significant in nondiabetic patients [OR 1.6; 95% CI, 1.3-2.1] than in diabetic patients (OR, 0.8; 95% CI, 0.6-1.0). Although the exact reason for this is unknown, existing theories include the following:

1. Diabetics are more apt to receive insulin for peri-operative hyperglycemia than nondiabetics (P<0.001);
2. Hyperglycemia in diabetics may be a less reliable marker of surgical stress than in nondiabetics; and
3. Diabetics may be better adapted to hyperglycemia than nondiabetics.

Bottom Line: Peri-operative hyperglycemia leads to an increased risk of adverse events; this relationship is more pronounced in nondiabetic patients than in diabetic patients.

Citation: Kotagal M, Symons RG, Hirsch IB, et al. Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg. 2015;261(1):97-103.

Clinical question: How does peri-operative hyperglycemia affect the risk of adverse events in diabetic patients compared to nondiabetic patients?

Background: Peri-operative hyperglycemia is associated with increased rates of infection, myocardial infarction, stroke, and death. Recent studies suggest that nondiabetics are more prone to hyperglycemia-related complications than diabetics. This study sought to analyze the effect and mechanism by which nondiabetics may be at increased risk for such complications.

Study Design: Retrospective cohort study.

Setting: Fifty-three hospitals in Washington.

Synopsis: Among 40,836 patients who underwent surgery, diabetics had a higher rate of peri-operative adverse events overall compared to nondiabetics (12% vs. 9%, P<0.001). Peri-operative hyperglycemia, defined as blood glucose 180 or greater, was also associated with an increased rate of adverse events. Ironically, this association was more significant in nondiabetic patients [OR 1.6; 95% CI, 1.3-2.1] than in diabetic patients (OR, 0.8; 95% CI, 0.6-1.0). Although the exact reason for this is unknown, existing theories include the following:

1. Diabetics are more apt to receive insulin for peri-operative hyperglycemia than nondiabetics (P<0.001);
2. Hyperglycemia in diabetics may be a less reliable marker of surgical stress than in nondiabetics; and
3. Diabetics may be better adapted to hyperglycemia than nondiabetics.

Bottom Line: Peri-operative hyperglycemia leads to an increased risk of adverse events; this relationship is more pronounced in nondiabetic patients than in diabetic patients.

Citation: Kotagal M, Symons RG, Hirsch IB, et al. Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg. 2015;261(1):97-103.

Clinical question: How does peri-operative hyperglycemia affect the risk of adverse events in diabetic patients compared to nondiabetic patients?

Background: Peri-operative hyperglycemia is associated with increased rates of infection, myocardial infarction, stroke, and death. Recent studies suggest that nondiabetics are more prone to hyperglycemia-related complications than diabetics. This study sought to analyze the effect and mechanism by which nondiabetics may be at increased risk for such complications.

Study Design: Retrospective cohort study.

Setting: Fifty-three hospitals in Washington.

Synopsis: Among 40,836 patients who underwent surgery, diabetics had a higher rate of peri-operative adverse events overall compared to nondiabetics (12% vs. 9%, P<0.001). Peri-operative hyperglycemia, defined as blood glucose 180 or greater, was also associated with an increased rate of adverse events. Ironically, this association was more significant in nondiabetic patients [OR 1.6; 95% CI, 1.3-2.1] than in diabetic patients (OR, 0.8; 95% CI, 0.6-1.0). Although the exact reason for this is unknown, existing theories include the following:

1. Diabetics are more apt to receive insulin for peri-operative hyperglycemia than nondiabetics (P<0.001);
2. Hyperglycemia in diabetics may be a less reliable marker of surgical stress than in nondiabetics; and
3. Diabetics may be better adapted to hyperglycemia than nondiabetics.

Bottom Line: Peri-operative hyperglycemia leads to an increased risk of adverse events; this relationship is more pronounced in nondiabetic patients than in diabetic patients.

Citation: Kotagal M, Symons RG, Hirsch IB, et al. Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg. 2015;261(1):97-103.

Clinical question: What is the impact of complaints on doctors’ psychological welfare and health?

Background: Studies have shown that malpractice litigation is associated with physician depression and suicide. Though complaints and investigations are part of appropriate physician oversight, unintentional consequences, such as defensive medicine and physician burnout, often occur.

Study design: Cross-sectional, anonymous survey study.

Setting: Surveys sent to members of the British Medical Association.

Synopsis: Only 8.3% of 95,636 invited physicians completed the survey. This study demonstrated that 16.9% of doctors with recent or ongoing complaints reported clinically significant symptoms of moderate to severe depression, compared to 9.5% of doctors with no complaints; 15% of doctors in the recent complaints group reported clinically significant levels of anxiety, compared to 7.3% of doctors with no complaints. Overall, 84.7% of doctors with a recent complaint and 79.9% with a past complaint reported changing the way they practiced medicine as a result of the complaint.

Since this study is a cross-sectional survey, it does not prove causation; it is possible that doctors with depression and anxiety are more likely to have complaints filed against them.

Bottom line: Doctors involved with complaints have a high prevalence of depression, anxiety, and suicidal ideation.

Citation: Bourne T, Wynants L, Peters M, et al. The impact of complaints procedures on the welfare, health and clinical practise of 7926 doctors in the UK: a cross-sectional survey. BMJ Open. 2015;5(1):e006687.

Clinical question: What is the impact of complaints on doctors’ psychological welfare and health?

Background: Studies have shown that malpractice litigation is associated with physician depression and suicide. Though complaints and investigations are part of appropriate physician oversight, unintentional consequences, such as defensive medicine and physician burnout, often occur.

Study design: Cross-sectional, anonymous survey study.

Setting: Surveys sent to members of the British Medical Association.

Synopsis: Only 8.3% of 95,636 invited physicians completed the survey. This study demonstrated that 16.9% of doctors with recent or ongoing complaints reported clinically significant symptoms of moderate to severe depression, compared to 9.5% of doctors with no complaints; 15% of doctors in the recent complaints group reported clinically significant levels of anxiety, compared to 7.3% of doctors with no complaints. Overall, 84.7% of doctors with a recent complaint and 79.9% with a past complaint reported changing the way they practiced medicine as a result of the complaint.

Since this study is a cross-sectional survey, it does not prove causation; it is possible that doctors with depression and anxiety are more likely to have complaints filed against them.

Bottom line: Doctors involved with complaints have a high prevalence of depression, anxiety, and suicidal ideation.

Citation: Bourne T, Wynants L, Peters M, et al. The impact of complaints procedures on the welfare, health and clinical practise of 7926 doctors in the UK: a cross-sectional survey. BMJ Open. 2015;5(1):e006687.

Clinical question: What is the impact of complaints on doctors’ psychological welfare and health?

Background: Studies have shown that malpractice litigation is associated with physician depression and suicide. Though complaints and investigations are part of appropriate physician oversight, unintentional consequences, such as defensive medicine and physician burnout, often occur.

Study design: Cross-sectional, anonymous survey study.

Setting: Surveys sent to members of the British Medical Association.

Synopsis: Only 8.3% of 95,636 invited physicians completed the survey. This study demonstrated that 16.9% of doctors with recent or ongoing complaints reported clinically significant symptoms of moderate to severe depression, compared to 9.5% of doctors with no complaints; 15% of doctors in the recent complaints group reported clinically significant levels of anxiety, compared to 7.3% of doctors with no complaints. Overall, 84.7% of doctors with a recent complaint and 79.9% with a past complaint reported changing the way they practiced medicine as a result of the complaint.

Since this study is a cross-sectional survey, it does not prove causation; it is possible that doctors with depression and anxiety are more likely to have complaints filed against them.

Bottom line: Doctors involved with complaints have a high prevalence of depression, anxiety, and suicidal ideation.

Citation: Bourne T, Wynants L, Peters M, et al. The impact of complaints procedures on the welfare, health and clinical practise of 7926 doctors in the UK: a cross-sectional survey. BMJ Open. 2015;5(1):e006687.

Clinical question: Does delirium contribute to chance of death?

Background: Delirium is a well-recognized predictor of mortality. Prior observational studies have estimated a risk of death two to four times higher in ICU patients with delirium compared with those who do not experience delirium. The degree to which this association reflects a causal relationship is debated.

Study design: Prospective cohort study; used logistic regression and competing risks survival analyses along with a marginal structural model analysis to adjust for both baseline characteristics and severity of illness developing during ICU stay.

Setting: Single ICU in the Netherlands.

Synopsis: Regression analysis of 1,112 ICU patients confirmed the strong association between delirium and mortality; however, additional analysis, adjusting for the severity of illness as it progressed during the ICU stay, attenuated the relationship to nonsignificance. This suggests that both delirium and mortality were being driven by the common underlying illness.

In post hoc analysis, only persistent delirium was associated with a small increase in mortality. Although this observational study can neither prove nor disprove causation, the adjustment for changing severity of illness during the ICU stay was more sophisticated than prior studies. This study suggests that delirium and mortality are likely companions on the road of critical illness but that one may not directly cause the other.

Bottom line: Delirium in the ICU likely does not cause death, but its presence portends increased risk of mortality.

Citations: Klouwenberg PM, Zaal IJ, Spitoni C, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652. Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922.

Clinical question: Does delirium contribute to chance of death?

Background: Delirium is a well-recognized predictor of mortality. Prior observational studies have estimated a risk of death two to four times higher in ICU patients with delirium compared with those who do not experience delirium. The degree to which this association reflects a causal relationship is debated.

Study design: Prospective cohort study; used logistic regression and competing risks survival analyses along with a marginal structural model analysis to adjust for both baseline characteristics and severity of illness developing during ICU stay.

Setting: Single ICU in the Netherlands.

Synopsis: Regression analysis of 1,112 ICU patients confirmed the strong association between delirium and mortality; however, additional analysis, adjusting for the severity of illness as it progressed during the ICU stay, attenuated the relationship to nonsignificance. This suggests that both delirium and mortality were being driven by the common underlying illness.

In post hoc analysis, only persistent delirium was associated with a small increase in mortality. Although this observational study can neither prove nor disprove causation, the adjustment for changing severity of illness during the ICU stay was more sophisticated than prior studies. This study suggests that delirium and mortality are likely companions on the road of critical illness but that one may not directly cause the other.

Bottom line: Delirium in the ICU likely does not cause death, but its presence portends increased risk of mortality.

Citations: Klouwenberg PM, Zaal IJ, Spitoni C, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652. Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922.

Clinical question: Does delirium contribute to chance of death?

Background: Delirium is a well-recognized predictor of mortality. Prior observational studies have estimated a risk of death two to four times higher in ICU patients with delirium compared with those who do not experience delirium. The degree to which this association reflects a causal relationship is debated.

Study design: Prospective cohort study; used logistic regression and competing risks survival analyses along with a marginal structural model analysis to adjust for both baseline characteristics and severity of illness developing during ICU stay.

Setting: Single ICU in the Netherlands.

Synopsis: Regression analysis of 1,112 ICU patients confirmed the strong association between delirium and mortality; however, additional analysis, adjusting for the severity of illness as it progressed during the ICU stay, attenuated the relationship to nonsignificance. This suggests that both delirium and mortality were being driven by the common underlying illness.

In post hoc analysis, only persistent delirium was associated with a small increase in mortality. Although this observational study can neither prove nor disprove causation, the adjustment for changing severity of illness during the ICU stay was more sophisticated than prior studies. This study suggests that delirium and mortality are likely companions on the road of critical illness but that one may not directly cause the other.

Bottom line: Delirium in the ICU likely does not cause death, but its presence portends increased risk of mortality.

Citations: Klouwenberg PM, Zaal IJ, Spitoni C, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652. Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922.

Clinical question: How does perioperative hyperglycemia affect the risk of adverse events in diabetic patients compared to nondiabetic patients?

Background: Perioperative hyperglycemia is associated with increased rates of infection, myocardial infarction, stroke, and death. Recent studies suggest that nondiabetics are more prone to hyperglycemia-related complications than diabetics. This study sought to analyze the effect and mechanism by which nondiabetics may be at increased risk for such complications.

Study design: Retrospective cohort study.

Setting: Fifty-three hospitals in Washington.

Synopsis: Among 40,836 patients who underwent surgery, diabetics had a higher rate of perioperative adverse events overall compared to nondiabetics (12% versus 9%, P<0.001). Perioperative hyperglycemia, defined as blood glucose 180 or greater, was also associated with an increased rate of adverse events. Ironically, this association was more significant in nondiabetic patients (odds ratio, 1.6; 95% CI, 1.3–2.1) than in diabetic patients (odds ratio, 0.8; 95% CI, 0.6–1.0). Although the exact reason for this is unknown, existing theories include the following:

• Diabetics are more apt to receive insulin for perioperative hyperglycemia than nondiabetics (P<0.001);
• Hyperglycemia in diabetics may be a less-reliable marker of surgical stress than in nondiabetics; and
• Diabetics may be better adapted to hyperglycemia than nondiabetics.

Bottom line: Perioperative hyperglycemia leads to an increased risk of adverse events; this relationship is more pronounced in nondiabetic patients than in diabetic patients.

Citation: Kotagal M, Symons RG, Hirsch IB, et al. Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg. 2015;261(1):97–103.  TH

Visit our website for more physician reviews of hospitalist-focused literature.

Clinical question: How does perioperative hyperglycemia affect the risk of adverse events in diabetic patients compared to nondiabetic patients?

Background: Perioperative hyperglycemia is associated with increased rates of infection, myocardial infarction, stroke, and death. Recent studies suggest that nondiabetics are more prone to hyperglycemia-related complications than diabetics. This study sought to analyze the effect and mechanism by which nondiabetics may be at increased risk for such complications.

Study design: Retrospective cohort study.

Setting: Fifty-three hospitals in Washington.

Synopsis: Among 40,836 patients who underwent surgery, diabetics had a higher rate of perioperative adverse events overall compared to nondiabetics (12% versus 9%, P<0.001). Perioperative hyperglycemia, defined as blood glucose 180 or greater, was also associated with an increased rate of adverse events. Ironically, this association was more significant in nondiabetic patients (odds ratio, 1.6; 95% CI, 1.3–2.1) than in diabetic patients (odds ratio, 0.8; 95% CI, 0.6–1.0). Although the exact reason for this is unknown, existing theories include the following:

• Diabetics are more apt to receive insulin for perioperative hyperglycemia than nondiabetics (P<0.001);
• Hyperglycemia in diabetics may be a less-reliable marker of surgical stress than in nondiabetics; and
• Diabetics may be better adapted to hyperglycemia than nondiabetics.

Bottom line: Perioperative hyperglycemia leads to an increased risk of adverse events; this relationship is more pronounced in nondiabetic patients than in diabetic patients.

Citation: Kotagal M, Symons RG, Hirsch IB, et al. Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg. 2015;261(1):97–103.  TH

Visit our website for more physician reviews of hospitalist-focused literature.

Clinical question: How does perioperative hyperglycemia affect the risk of adverse events in diabetic patients compared to nondiabetic patients?

Background: Perioperative hyperglycemia is associated with increased rates of infection, myocardial infarction, stroke, and death. Recent studies suggest that nondiabetics are more prone to hyperglycemia-related complications than diabetics. This study sought to analyze the effect and mechanism by which nondiabetics may be at increased risk for such complications.

Study design: Retrospective cohort study.

Setting: Fifty-three hospitals in Washington.

Synopsis: Among 40,836 patients who underwent surgery, diabetics had a higher rate of perioperative adverse events overall compared to nondiabetics (12% versus 9%, P<0.001). Perioperative hyperglycemia, defined as blood glucose 180 or greater, was also associated with an increased rate of adverse events. Ironically, this association was more significant in nondiabetic patients (odds ratio, 1.6; 95% CI, 1.3–2.1) than in diabetic patients (odds ratio, 0.8; 95% CI, 0.6–1.0). Although the exact reason for this is unknown, existing theories include the following:

• Diabetics are more apt to receive insulin for perioperative hyperglycemia than nondiabetics (P<0.001);
• Hyperglycemia in diabetics may be a less-reliable marker of surgical stress than in nondiabetics; and
• Diabetics may be better adapted to hyperglycemia than nondiabetics.

Bottom line: Perioperative hyperglycemia leads to an increased risk of adverse events; this relationship is more pronounced in nondiabetic patients than in diabetic patients.

Citation: Kotagal M, Symons RG, Hirsch IB, et al. Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg. 2015;261(1):97–103.  TH

Visit our website for more physician reviews of hospitalist-focused literature.

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56–1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: Comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Visit our website for more information on the use of proton pump inhibitors.

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56–1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: Comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Visit our website for more information on the use of proton pump inhibitors.

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56–1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: Comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Visit our website for more information on the use of proton pump inhibitors.

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Visit our website for more information on treating delirium in hospitalized patients.

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Visit our website for more information on treating delirium in hospitalized patients.

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Visit our website for more information on treating delirium in hospitalized patients.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Intravenous haloperidol does not prevent ICU delirium
2. Predicting delirium risk in hospitalized adults
3. Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
4. Probiotic benefit questioned in the elderly
5. Colchicine and NSAID better than NSAID alone for acute pericarditis
6. Improvement needed in patient understanding at hospital discharge
7. Effectiveness of a multihospital effort to reduce rehospitalization
8. Hospitals profit from preventing surgical site infections
9. Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
10. Hospital-acquired anemia associated with higher mortality, increased LOS
11. Thrombolytics and stroke: the faster the better

Intravenous Haloperidol Does Not Prevent ICU Delirium

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Predicting Delirium Risk in Hospitalized Adults

Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?

Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.

Study design: Prospective cohort study, with separate derivation and validation cohorts.

Setting: Two academic hospitals and a VA hospital in San Francisco.

Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).

These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.

Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.

Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.

Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Probiotic Benefit Questioned in the Elderly

Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?

Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.

Study Design: Randomized, double-blind, placebo-controlled trial.

Setting: Multicenter trial in the United Kingdom.

Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).

Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.

Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.

Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.

Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis

Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?

Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.

Study design: Double-blinded, randomized, controlled trial.

Setting: Multicenter in Northern Italy.

Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.

It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.

Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.

Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.

Improvement Needed in Patient Understanding at Hospital Discharge

Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?

Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.

Study Design: Prospective, observational cohort study.

Setting: An urban, academic medical center.

Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.

Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.

Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.

Effectiveness of a Multihospital Effort to Reduce Rehospitalization

Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?

Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.

Study design: Semi-controlled, pre-post study.

Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.

Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.

Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).

Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.

Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.

Hospitals Profit from Preventing Surgical Site Infections

Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?

Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.

Study design: Retrospective study.

Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.

Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.

Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.

Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.

Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR

Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?

Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.

Study design: Retrospective cohort study.

Setting: Two tertiary care EDs in Canada.

Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.

Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.

Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.

Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.

Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS

Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?

Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.

Study design: Retrospective cohort study.

Setting: Large academic health system in Ohio.

Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.

Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.

Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.

Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.

Thrombolytics and Stroke: The Faster the Better

Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?

Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.

Study design: Observational study.

Setting: Patient information from 1998 to 2012 from 10 European stroke centers.

Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.

Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.

Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.

Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Intravenous haloperidol does not prevent ICU delirium
2. Predicting delirium risk in hospitalized adults
3. Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
4. Probiotic benefit questioned in the elderly
5. Colchicine and NSAID better than NSAID alone for acute pericarditis
6. Improvement needed in patient understanding at hospital discharge
7. Effectiveness of a multihospital effort to reduce rehospitalization
8. Hospitals profit from preventing surgical site infections
9. Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
10. Hospital-acquired anemia associated with higher mortality, increased LOS
11. Thrombolytics and stroke: the faster the better

Intravenous Haloperidol Does Not Prevent ICU Delirium

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Predicting Delirium Risk in Hospitalized Adults

Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?

Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.

Study design: Prospective cohort study, with separate derivation and validation cohorts.

Setting: Two academic hospitals and a VA hospital in San Francisco.

Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).

These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.

Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.

Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.

Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Probiotic Benefit Questioned in the Elderly

Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?

Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.

Study Design: Randomized, double-blind, placebo-controlled trial.

Setting: Multicenter trial in the United Kingdom.

Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).

Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.

Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.

Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.

Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis

Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?

Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.

Study design: Double-blinded, randomized, controlled trial.

Setting: Multicenter in Northern Italy.

Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.

It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.

Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.

Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.

Improvement Needed in Patient Understanding at Hospital Discharge

Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?

Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.

Study Design: Prospective, observational cohort study.

Setting: An urban, academic medical center.

Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.

Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.

Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.

Effectiveness of a Multihospital Effort to Reduce Rehospitalization

Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?

Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.

Study design: Semi-controlled, pre-post study.

Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.

Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.

Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).

Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.

Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.

Hospitals Profit from Preventing Surgical Site Infections

Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?

Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.

Study design: Retrospective study.

Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.

Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.

Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.

Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.

Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR

Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?

Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.

Study design: Retrospective cohort study.

Setting: Two tertiary care EDs in Canada.

Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.

Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.

Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.

Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.

Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS

Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?

Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.

Study design: Retrospective cohort study.

Setting: Large academic health system in Ohio.

Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.

Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.

Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.

Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.

Thrombolytics and Stroke: The Faster the Better

Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?

Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.

Study design: Observational study.

Setting: Patient information from 1998 to 2012 from 10 European stroke centers.

Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.

Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.

Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.

Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Intravenous haloperidol does not prevent ICU delirium
2. Predicting delirium risk in hospitalized adults
3. Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
4. Probiotic benefit questioned in the elderly
5. Colchicine and NSAID better than NSAID alone for acute pericarditis
6. Improvement needed in patient understanding at hospital discharge
7. Effectiveness of a multihospital effort to reduce rehospitalization
8. Hospitals profit from preventing surgical site infections
9. Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
10. Hospital-acquired anemia associated with higher mortality, increased LOS
11. Thrombolytics and stroke: the faster the better

Intravenous Haloperidol Does Not Prevent ICU Delirium

Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?

Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Single, adult ICU in England.

Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.

This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.

Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.

Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.

Predicting Delirium Risk in Hospitalized Adults

Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?

Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.

Study design: Prospective cohort study, with separate derivation and validation cohorts.

Setting: Two academic hospitals and a VA hospital in San Francisco.

Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).

These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.

Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.

Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.

Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding

Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?

Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.

Study design: Meta-analysis of prospective, randomized control trials.

Setting: OVID database search in June 2012.

Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).

Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.

Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.

Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.

Probiotic Benefit Questioned in the Elderly

Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?

Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.

Study Design: Randomized, double-blind, placebo-controlled trial.

Setting: Multicenter trial in the United Kingdom.

Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).

Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.

Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.

Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.

Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis

Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?

Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.

Study design: Double-blinded, randomized, controlled trial.

Setting: Multicenter in Northern Italy.

Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.

It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.

Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.

Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.

Improvement Needed in Patient Understanding at Hospital Discharge

Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?

Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.

Study Design: Prospective, observational cohort study.

Setting: An urban, academic medical center.

Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.

Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.

Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.

Effectiveness of a Multihospital Effort to Reduce Rehospitalization

Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?

Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.

Study design: Semi-controlled, pre-post study.

Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.

Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.

Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).

Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.

Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.

Hospitals Profit from Preventing Surgical Site Infections

Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?

Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.

Study design: Retrospective study.

Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.

Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.

Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.

The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.

Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.

Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.

Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR

Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?

Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.

Study design: Retrospective cohort study.

Setting: Two tertiary care EDs in Canada.

Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.

Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.

Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.

Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.

Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS

Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?

Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.

Study design: Retrospective cohort study.

Setting: Large academic health system in Ohio.

Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.

Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.

Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.

Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.

Thrombolytics and Stroke: The Faster the Better

Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?

Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.

Study design: Observational study.

Setting: Patient information from 1998 to 2012 from 10 European stroke centers.

Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.

Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.

Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.

Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.

For more physician reviews of recent HM-relevant literature, visit our website.

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.

For more physician reviews of recent HM-relevant literature, visit our website.

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.Am J Med. 2012;125(5):505-511.

For more physician reviews of recent HM-relevant literature, visit our website.