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In the Literature
In This Edition
Literature at a Glance
A guide to this month’s studies
- Antibiotics after drainage of uncomplicated skin abscesses
- Clopidogrel vs. combined aspirin-dipyridamole for acute ischemic stroke
- BNP-guided therapy in chronic heart failure outpatients
- Cognitive decline and dementia after hospitalization
- Clopidogrel delays up risks for DES implantation patients
- Clinical score identifies prolonged length of stay
- Time to therapy reduces mortality in sepsis patients
- PEEP associated with lower mortality for ARDS patients
Antibiotics Might Be Unnecessary after Drainage of Uncomplicated Skin Abscesses
Clinical question: Does trimethoprim/sulfamethoxazole (TMP/SMX) treatment after drainage of a skin abscess reduce treatment failure at seven days or development of new lesions at 30 days?
Background: Community ac-quired methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses are increasing in frequency. The benefit of antibiotic treatment after incision and drainage is not clear, as there is a high cure rate without antibiotics.
Study design: Multicenter, double-blinded, randomized, placebo-controlled trial.
Setting: Four military EDs treating civilians and military patients.
Synopsis: The study enrolled a convenience sample of 220 patients, each of whom presented to EDs with uncomplicated skin abscesses from November 2007 to June 2009. Abscesses were drained in the ED, then patients were randomized to either placebo or to TMP/SMX (two DS tablets twice daily) for seven days. Re-evaluation for wound checks occurred at two days and seven days.
Treatment failure at seven days, defined as worsening infection, new lesions, or absence of clinical improvement, occurred in 26% of placebo patients and 17% of patients in the treatment arm, a nonsignificant difference (P=0.12). Fewer patients in the treatment arm had new lesions at 30 days (28% vs. 9%, P=0.02). MRSA was cultured from 53% of patients overall; all samples were sensitive to TMP/SMX.
The study was limited by the fact that only 69% of patients were evaluated at 30 days.
Bottom line: TMP/SMX treatment of uncomplicated skin abscess after drainage in EDs does not decrease treatment failure at seven days, but might decrease the development of new lesions.
Citation: Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection [published online ahead of print March 29, 2010]. Ann Emerg Med. doi:10.1016/j.annemerg med.2010.03.002.
Clopidogrel and Combined Aspirin-Dipyridamole Have Similar Safety and Efficacy Profiles for Acute Ischemic Stroke
Clinical question: What is the efficacy and safety of combined aspirin and extended-release dipyridamole (Asp/ER-DP) compared to clopidogrel in patients with acute ischemic stroke?
Background: Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of Asp/ER-DP or clopidogrel is not known in patients with acute ischemic stroke.
Study design: Randomized, controlled trial.
Setting: A multicenter trial involving 695 sites in 35 countries.
Synopsis: This post-hoc subgroup analysis of the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial assessed the relative safety and efficacy of Asp/ER-DP versus clopidogrel administered within 72 hours of stroke onset in 1,360 patients. The primary endpoint was functional outcome at 30 days.
Secondary outcomes included symptomatic hemorrhagic transformation of the infarct, cerebral edema, recurrent stroke, myocardial infarction (MI), composite vascular events (combination of nonfatal stroke, nonfatal MI, and vascular death), death, cognition, bleeding, and serious adverse events studied at seven, 30, and 90 days.
Combined death or dependency did not differ between treatment groups. Nonsignificant trends to reduced recurrence and vascular events were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups.
Bottom line: Either clopidogrel or combined aspirin and extended-release dipyridamole can be used to treat acute ischemic stroke, with similar outcomes and safety profiles.
Citation: Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis. Stroke. 2010;41(4):732-738.
BNP-Guided Therapy Reduces All-Cause Mortality in Outpatients with Chronic Heart Failure
Clinical question: Is there a clinical benefit in using B-type natriuretic peptide (BNP) to guide adjustment of proven medications in chronic heart failure?
Background: BNP is secreted by the heart in response to increased volume. It has been shown to be useful in the diagnosis of decompensated heart failure, and it can be decreased by treatment with proven heart failure medications. It is unclear if this effect provides clinical benefit on mortality and hospitalization.
Study design: Meta-analysis of prospective randomized controlled trials.
Setting: Eight studies involving 1,726 patients, published internationally from 2005-2009.
Synopsis: Study sizes ranged from 41 to 499 patients, with three- to 24-month follow-up. Patients had New York Heart Association (NYHA) class II or greater heart failure, with ejection fractions <50%.
All-cause mortality was significantly lower in BNP-guided therapy compared with clinical-guided therapy (RR=0.76; 95% CI, 0.63-0.91; P=0.003), specifically in patients younger than 75 years old (RR=0.52; 95% CI, 0.33-0.82; P=0.005).
A proposed mechanism for this result was a statistically significant increase in adjustment of most heart failure medications for BNP-guided therapy compared with clinical-guided therapy (75% vs. 58%, P<0.001 in diuretics; 49.6% vs. 30.9%, P<0.001 in ACE inhibitors or Angiotensin II receptor blockers (ARBs); and 51.1% vs. 41.6%, P=0.02 in beta-blockers) and a higher percentage reaching target doses in the BNP-guided therapy group. However, there was no significant decrease in all-cause hospitalization or survival free of hospitalization.
The study limitations include: Hospitalization for heart failure was not meta-analyzed, the pooled data were weighted toward one study, and BNP-guided titration parameters varied across studies.
Bottom line: BNP-guided therapy reduces all-cause mortality in chronic heart failure patients younger than 75 years old, but not all-cause hospitalization or survival free of hospitalization.
Citation: Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med. 2010;170(6):507-514.
Hospitalization Is Associated with Cognitive Decline and Subsequent Risk for Dementia in the Elderly
Clinical question: Is critical illness in patients 65 and older associated with long-term cognitive impairment, and does it affect the incidence of dementia?
Background: There is literature suggesting that survivors of critical illness suffer long-term cognitive impairment, but premorbid measures of cognitive function have not been researched. No studies have evaluated the risk of incident dementia among this patient population.
Study design: Prospective cohort study.
Setting: Group Health Cooperative in Seattle.
Synopsis: This study analyzed data from 2,929 community-dwelling adults older than 65 without baseline dementia. From 1994 to 2007, the individuals were screened with the Cognitive Abilities Screening Instrument (CASI) at follow-up visits every two years. CASI scores lower than 86 (out of 100) led to an examination for dementia; the diagnosis of dementia was an outcome measure. Scores were adjusted for baseline cognitive scores, age, and other risk factors.
For patients following acute-care hospitalization, adjusted CASI scores were 1.01 points lower on average than for those not hospitalized. For patients following critical-illness hospitalization, scores were 2.14 points lower. The dementia rate was 14.6 cases per 1,000 person-years among patients not hospitalized, and 33.6 among those admitted for noncritical illness.
As suspected, hospitalization might be a marker for cognitive decline in the elderly after adjusting for premorbid CASI scores and comorbid illness. Some factors in acute illness—and moreso in critical illness—might be causally related to cognitive decline.
Bottom line: In elderly patients without dementia at baseline, hospitalization for acute care and critical illness increases the likelihood of cognitive decline compared with patients who were not hospitalized. Only noncritical-illness hospitalization was not associated with the development of dementia.
Citation: Ehlenbach WJ, Hough CL, Crane PK, et al. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA. 2010;303(8): 763-770.
Increased Risk of Death and Myocardial Infarction in Patients Who Delay Filling Clopidogrel Prescription after Drug-Eluting Stent Implantation
Clinical question: Is there an increased risk of death or myocardial infarction (MI) in patients with recent drug-eluting stent (DES) implantation who delayed filling their clopidogrel prescription compared with those who filled their prescription on the day of hospital discharge?
Background: Filling an initial prescription of clopidogrel on the day of discharge is important after DES implantation, as prior studies suggest that lack of thienopyridine therapy is a risk factor for early stent thrombosis.
Study design: Retrospective cohort study.
Setting: Three large, integrated healthcare systems.
Synopsis: The cohort included 7,042 patients discharged after DES implantation. Filling of a clopidogrel prescription was based on pharmacy dispensing data. Primary analysis divided patients based on whether they filled the prescription on the day of discharge or any time after discharge. Secondary analysis further characterized delays as >1 day, >3 days, or >5 days after discharge.
One in 6 patients delayed filling the initial prescription. Patients with any degree of delay had significantly higher death and MI rates during follow-up (14.2% vs. 7.9%, P<0.001), as well as an increased risk of death/MI (hazard ratio 1.53; 95% CI, 1.25-1.87). Factors associated with a delay in filling clopidogrel included older age, prior MI, diabetes, renal dysfunction, prior revascularization, cardiogenic shock, in-hospital bleeding, and use of clopidogrel upon admission.
The study was limited in that data were based on pharmacy records, and that patients might have received medication at discharge or outside the healthcare system.
Bottom line: The delay in filling a clopidogrel prescription is associated with an increased risk of death and MI in patients with recent DES implantation.
Citation: Ho PM, Tsai TT, Maddox TM, et al. Delays in filling clopidogrel prescription after hospital discharge and adverse outcomes after drug-eluting stent implantation: implications for transitions of care. Circ Cardiovasc Qual Outcomes. 2010;3(3):261-266.
Predicting Length of Stay after Stroke
Clinical question: Does a clinical score accurately predict prolonged length of stay after stroke?
Background: Stroke is a costly health problem, and length of stay is the most prominent factor contributing to the high costs. The factors leading to prolonged length of stay are varied, and there are no established tools to predict length of stay.
Study design: Prospective cohort study.
Setting: All 28 Israeli hospitals that admit stroke patients.
Synopsis: All patients admitted to Israeli hospitals during established two-month periods in 2004 (1,700 patients) and 2007 (1,648 patients) were included in the National Acute Stroke Israeli Survey (NASIS), and served as the derivation and validation cohort for development of a Prolonged Length of Stay (PLOS) score.
Using the 2004 data, investigators identified stroke severity using the National Institutes of Health Stroke Scale (NIHSS), history of congestive heart failure (CHF), history of atrial fibrillation, decreased level of consciousness on presentation, and intracerebral hemorrhage (as opposed to ischemic stroke) as predictors of prolonged length of stay. Four of these factors were expressed as dichotomous variables, whereas the stroke severity by NIHSS class was incorporated as a range; all were incorporated into a PLOS score.
Higher PLOS score correlated with longer length of stay. In the derivation cohort, 22% of patients with a PLOS score of 0 had a prolonged length of stay, whereas 85% of patients with PLOS scores of 6 or 7 had a prolonged length of stay. In the validation cohort, the corresponding figures were 19% and 72%.
Bottom line: Use of a simple score can predict risk of prolonged length of stay after stroke.
Citation: Koton S, Bornstein NM, Tsabari R, Tanne D, NASIS Investigators. Derivation and validation of the prolonged length of stay score in acute stroke patients. Neurology. 2010;74(19);1511-1516.
Earlier Administration of Appropriate Antimicrobials Decreases Mortality in Patients with Severe Sepsis and Septic Shock
Clinical question: Is the timing of antimicrobial administration an important determinant of survival in patients diagnosed with severe sepsis and septic shock?
Background: Severe sepsis and septic shock are associated with a 25% to 50% mortality rate. Early goal-directed therapy has been shown to increase survival in these patients. Antimicrobial treatment is a mainstay of this therapy, but the most effective timing of this treatment remains unclear.
Study design: Retrospective, single-center cohort study.
Setting: ED at an academic tertiary-care center.
Synopsis: Two hundred sixty-one patients in the ED in 2005-2006 presenting with severe sepsis or septic shock were enrolled in the hospital’s early goal-directed therapy (EGDT) algorithm, either at triage or later during their ED stay. Labs showed 56.7% of patients were culture-positive, with the most common sources being respiratory (30.6%), genitourinary (22.8%), and gastrointestinal (19.7%).
All patients received antibiotics and were stratified in one-hour intervals by the following categories: time from triage to antibiotics; time from qualification for EGDT to antibiotics; time from triage to appropriate antibiotics; and time from qualification for EGDT to appropriate antibiotics.
Total in-hospital mortality was 31% (35.1% for culture-positive patients vs. 25.7% for culture-negative patients, P=0.11). A significant decrease in mortality was only found when appropriate antibiotics were administered within one hour of triage, or within one hour of qualification for EGDT (OR=0.30; 95% CI, 0.11-0.83; P=0.02, and OR=0.50; 95% CI, 0.27-0.92; P=0.03, respectively).
Study limitations included the single-center site and small sample size.
Bottom line: In patients with severe sepsis and septic shock, initiating appropriate antimicrobial therapy within one hour of triage or entry into goal-directed therapy significantly reduces mortality.
Citation: Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053.
Treatment with Higher Levels of Positive End-Expiratory Pressure Has Limited Affect on Hospital Survival
Clinical question: Is treatment with higher versus lower levels of positive end-expiratory pressure (PEEP) associated with improved hospital survival?
Background: In the management of patients with acute lung injury or acute respiratory distress syndrome (ARDS), a fundamental goal is to protect the lungs from ventilation-induced injury, but the optimal PEEP level has not been established.
Study design: Systematic review and meta-analysis.
Setting: N/A.
Synopsis: Three randomized-controlled trials eligible for this review included 2,299 critically ill adults with acute lung injury, as defined by the American-European Consensus Conference. The meta-analysis compared higher and lower PEEP levels with a mean difference of at least 3 cm H2O, incorporated a target tidal volume of less than 8 mL/kg of predicted body weight in both ventilation strategies, and provided patient follow-up until death or for at least 20 days.
This review demonstrated no statistically significant difference in hospital mortality between the groups. However, in patients with ARDS, higher levels of PEEP were associated with a relative reduction in mortality of 10%. This is supported by a recent cohort study in patients with acute lung injury or ARDS, which showed that the effect of PEEP on lung recruitment was associated with the proportion of potentially recruitable lung, as determined by computed tomography.
Since patients with ARDS have more pulmonary edema than those with acute lung injury without ARDS, the former have greater recruitability, and thus might benefit more from higher levels of PEEP.
Bottom line: Higher levels of PEEP might be associated with lower hospital mortality in patients with ARDS, but such a benefit is unlikely in patients with less severe lung injuries, and could actually be harmful.
Citation: Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865-873. TH
In This Edition
Literature at a Glance
A guide to this month’s studies
- Antibiotics after drainage of uncomplicated skin abscesses
- Clopidogrel vs. combined aspirin-dipyridamole for acute ischemic stroke
- BNP-guided therapy in chronic heart failure outpatients
- Cognitive decline and dementia after hospitalization
- Clopidogrel delays up risks for DES implantation patients
- Clinical score identifies prolonged length of stay
- Time to therapy reduces mortality in sepsis patients
- PEEP associated with lower mortality for ARDS patients
Antibiotics Might Be Unnecessary after Drainage of Uncomplicated Skin Abscesses
Clinical question: Does trimethoprim/sulfamethoxazole (TMP/SMX) treatment after drainage of a skin abscess reduce treatment failure at seven days or development of new lesions at 30 days?
Background: Community ac-quired methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses are increasing in frequency. The benefit of antibiotic treatment after incision and drainage is not clear, as there is a high cure rate without antibiotics.
Study design: Multicenter, double-blinded, randomized, placebo-controlled trial.
Setting: Four military EDs treating civilians and military patients.
Synopsis: The study enrolled a convenience sample of 220 patients, each of whom presented to EDs with uncomplicated skin abscesses from November 2007 to June 2009. Abscesses were drained in the ED, then patients were randomized to either placebo or to TMP/SMX (two DS tablets twice daily) for seven days. Re-evaluation for wound checks occurred at two days and seven days.
Treatment failure at seven days, defined as worsening infection, new lesions, or absence of clinical improvement, occurred in 26% of placebo patients and 17% of patients in the treatment arm, a nonsignificant difference (P=0.12). Fewer patients in the treatment arm had new lesions at 30 days (28% vs. 9%, P=0.02). MRSA was cultured from 53% of patients overall; all samples were sensitive to TMP/SMX.
The study was limited by the fact that only 69% of patients were evaluated at 30 days.
Bottom line: TMP/SMX treatment of uncomplicated skin abscess after drainage in EDs does not decrease treatment failure at seven days, but might decrease the development of new lesions.
Citation: Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection [published online ahead of print March 29, 2010]. Ann Emerg Med. doi:10.1016/j.annemerg med.2010.03.002.
Clopidogrel and Combined Aspirin-Dipyridamole Have Similar Safety and Efficacy Profiles for Acute Ischemic Stroke
Clinical question: What is the efficacy and safety of combined aspirin and extended-release dipyridamole (Asp/ER-DP) compared to clopidogrel in patients with acute ischemic stroke?
Background: Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of Asp/ER-DP or clopidogrel is not known in patients with acute ischemic stroke.
Study design: Randomized, controlled trial.
Setting: A multicenter trial involving 695 sites in 35 countries.
Synopsis: This post-hoc subgroup analysis of the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial assessed the relative safety and efficacy of Asp/ER-DP versus clopidogrel administered within 72 hours of stroke onset in 1,360 patients. The primary endpoint was functional outcome at 30 days.
Secondary outcomes included symptomatic hemorrhagic transformation of the infarct, cerebral edema, recurrent stroke, myocardial infarction (MI), composite vascular events (combination of nonfatal stroke, nonfatal MI, and vascular death), death, cognition, bleeding, and serious adverse events studied at seven, 30, and 90 days.
Combined death or dependency did not differ between treatment groups. Nonsignificant trends to reduced recurrence and vascular events were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups.
Bottom line: Either clopidogrel or combined aspirin and extended-release dipyridamole can be used to treat acute ischemic stroke, with similar outcomes and safety profiles.
Citation: Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis. Stroke. 2010;41(4):732-738.
BNP-Guided Therapy Reduces All-Cause Mortality in Outpatients with Chronic Heart Failure
Clinical question: Is there a clinical benefit in using B-type natriuretic peptide (BNP) to guide adjustment of proven medications in chronic heart failure?
Background: BNP is secreted by the heart in response to increased volume. It has been shown to be useful in the diagnosis of decompensated heart failure, and it can be decreased by treatment with proven heart failure medications. It is unclear if this effect provides clinical benefit on mortality and hospitalization.
Study design: Meta-analysis of prospective randomized controlled trials.
Setting: Eight studies involving 1,726 patients, published internationally from 2005-2009.
Synopsis: Study sizes ranged from 41 to 499 patients, with three- to 24-month follow-up. Patients had New York Heart Association (NYHA) class II or greater heart failure, with ejection fractions <50%.
All-cause mortality was significantly lower in BNP-guided therapy compared with clinical-guided therapy (RR=0.76; 95% CI, 0.63-0.91; P=0.003), specifically in patients younger than 75 years old (RR=0.52; 95% CI, 0.33-0.82; P=0.005).
A proposed mechanism for this result was a statistically significant increase in adjustment of most heart failure medications for BNP-guided therapy compared with clinical-guided therapy (75% vs. 58%, P<0.001 in diuretics; 49.6% vs. 30.9%, P<0.001 in ACE inhibitors or Angiotensin II receptor blockers (ARBs); and 51.1% vs. 41.6%, P=0.02 in beta-blockers) and a higher percentage reaching target doses in the BNP-guided therapy group. However, there was no significant decrease in all-cause hospitalization or survival free of hospitalization.
The study limitations include: Hospitalization for heart failure was not meta-analyzed, the pooled data were weighted toward one study, and BNP-guided titration parameters varied across studies.
Bottom line: BNP-guided therapy reduces all-cause mortality in chronic heart failure patients younger than 75 years old, but not all-cause hospitalization or survival free of hospitalization.
Citation: Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med. 2010;170(6):507-514.
Hospitalization Is Associated with Cognitive Decline and Subsequent Risk for Dementia in the Elderly
Clinical question: Is critical illness in patients 65 and older associated with long-term cognitive impairment, and does it affect the incidence of dementia?
Background: There is literature suggesting that survivors of critical illness suffer long-term cognitive impairment, but premorbid measures of cognitive function have not been researched. No studies have evaluated the risk of incident dementia among this patient population.
Study design: Prospective cohort study.
Setting: Group Health Cooperative in Seattle.
Synopsis: This study analyzed data from 2,929 community-dwelling adults older than 65 without baseline dementia. From 1994 to 2007, the individuals were screened with the Cognitive Abilities Screening Instrument (CASI) at follow-up visits every two years. CASI scores lower than 86 (out of 100) led to an examination for dementia; the diagnosis of dementia was an outcome measure. Scores were adjusted for baseline cognitive scores, age, and other risk factors.
For patients following acute-care hospitalization, adjusted CASI scores were 1.01 points lower on average than for those not hospitalized. For patients following critical-illness hospitalization, scores were 2.14 points lower. The dementia rate was 14.6 cases per 1,000 person-years among patients not hospitalized, and 33.6 among those admitted for noncritical illness.
As suspected, hospitalization might be a marker for cognitive decline in the elderly after adjusting for premorbid CASI scores and comorbid illness. Some factors in acute illness—and moreso in critical illness—might be causally related to cognitive decline.
Bottom line: In elderly patients without dementia at baseline, hospitalization for acute care and critical illness increases the likelihood of cognitive decline compared with patients who were not hospitalized. Only noncritical-illness hospitalization was not associated with the development of dementia.
Citation: Ehlenbach WJ, Hough CL, Crane PK, et al. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA. 2010;303(8): 763-770.
Increased Risk of Death and Myocardial Infarction in Patients Who Delay Filling Clopidogrel Prescription after Drug-Eluting Stent Implantation
Clinical question: Is there an increased risk of death or myocardial infarction (MI) in patients with recent drug-eluting stent (DES) implantation who delayed filling their clopidogrel prescription compared with those who filled their prescription on the day of hospital discharge?
Background: Filling an initial prescription of clopidogrel on the day of discharge is important after DES implantation, as prior studies suggest that lack of thienopyridine therapy is a risk factor for early stent thrombosis.
Study design: Retrospective cohort study.
Setting: Three large, integrated healthcare systems.
Synopsis: The cohort included 7,042 patients discharged after DES implantation. Filling of a clopidogrel prescription was based on pharmacy dispensing data. Primary analysis divided patients based on whether they filled the prescription on the day of discharge or any time after discharge. Secondary analysis further characterized delays as >1 day, >3 days, or >5 days after discharge.
One in 6 patients delayed filling the initial prescription. Patients with any degree of delay had significantly higher death and MI rates during follow-up (14.2% vs. 7.9%, P<0.001), as well as an increased risk of death/MI (hazard ratio 1.53; 95% CI, 1.25-1.87). Factors associated with a delay in filling clopidogrel included older age, prior MI, diabetes, renal dysfunction, prior revascularization, cardiogenic shock, in-hospital bleeding, and use of clopidogrel upon admission.
The study was limited in that data were based on pharmacy records, and that patients might have received medication at discharge or outside the healthcare system.
Bottom line: The delay in filling a clopidogrel prescription is associated with an increased risk of death and MI in patients with recent DES implantation.
Citation: Ho PM, Tsai TT, Maddox TM, et al. Delays in filling clopidogrel prescription after hospital discharge and adverse outcomes after drug-eluting stent implantation: implications for transitions of care. Circ Cardiovasc Qual Outcomes. 2010;3(3):261-266.
Predicting Length of Stay after Stroke
Clinical question: Does a clinical score accurately predict prolonged length of stay after stroke?
Background: Stroke is a costly health problem, and length of stay is the most prominent factor contributing to the high costs. The factors leading to prolonged length of stay are varied, and there are no established tools to predict length of stay.
Study design: Prospective cohort study.
Setting: All 28 Israeli hospitals that admit stroke patients.
Synopsis: All patients admitted to Israeli hospitals during established two-month periods in 2004 (1,700 patients) and 2007 (1,648 patients) were included in the National Acute Stroke Israeli Survey (NASIS), and served as the derivation and validation cohort for development of a Prolonged Length of Stay (PLOS) score.
Using the 2004 data, investigators identified stroke severity using the National Institutes of Health Stroke Scale (NIHSS), history of congestive heart failure (CHF), history of atrial fibrillation, decreased level of consciousness on presentation, and intracerebral hemorrhage (as opposed to ischemic stroke) as predictors of prolonged length of stay. Four of these factors were expressed as dichotomous variables, whereas the stroke severity by NIHSS class was incorporated as a range; all were incorporated into a PLOS score.
Higher PLOS score correlated with longer length of stay. In the derivation cohort, 22% of patients with a PLOS score of 0 had a prolonged length of stay, whereas 85% of patients with PLOS scores of 6 or 7 had a prolonged length of stay. In the validation cohort, the corresponding figures were 19% and 72%.
Bottom line: Use of a simple score can predict risk of prolonged length of stay after stroke.
Citation: Koton S, Bornstein NM, Tsabari R, Tanne D, NASIS Investigators. Derivation and validation of the prolonged length of stay score in acute stroke patients. Neurology. 2010;74(19);1511-1516.
Earlier Administration of Appropriate Antimicrobials Decreases Mortality in Patients with Severe Sepsis and Septic Shock
Clinical question: Is the timing of antimicrobial administration an important determinant of survival in patients diagnosed with severe sepsis and septic shock?
Background: Severe sepsis and septic shock are associated with a 25% to 50% mortality rate. Early goal-directed therapy has been shown to increase survival in these patients. Antimicrobial treatment is a mainstay of this therapy, but the most effective timing of this treatment remains unclear.
Study design: Retrospective, single-center cohort study.
Setting: ED at an academic tertiary-care center.
Synopsis: Two hundred sixty-one patients in the ED in 2005-2006 presenting with severe sepsis or septic shock were enrolled in the hospital’s early goal-directed therapy (EGDT) algorithm, either at triage or later during their ED stay. Labs showed 56.7% of patients were culture-positive, with the most common sources being respiratory (30.6%), genitourinary (22.8%), and gastrointestinal (19.7%).
All patients received antibiotics and were stratified in one-hour intervals by the following categories: time from triage to antibiotics; time from qualification for EGDT to antibiotics; time from triage to appropriate antibiotics; and time from qualification for EGDT to appropriate antibiotics.
Total in-hospital mortality was 31% (35.1% for culture-positive patients vs. 25.7% for culture-negative patients, P=0.11). A significant decrease in mortality was only found when appropriate antibiotics were administered within one hour of triage, or within one hour of qualification for EGDT (OR=0.30; 95% CI, 0.11-0.83; P=0.02, and OR=0.50; 95% CI, 0.27-0.92; P=0.03, respectively).
Study limitations included the single-center site and small sample size.
Bottom line: In patients with severe sepsis and septic shock, initiating appropriate antimicrobial therapy within one hour of triage or entry into goal-directed therapy significantly reduces mortality.
Citation: Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053.
Treatment with Higher Levels of Positive End-Expiratory Pressure Has Limited Affect on Hospital Survival
Clinical question: Is treatment with higher versus lower levels of positive end-expiratory pressure (PEEP) associated with improved hospital survival?
Background: In the management of patients with acute lung injury or acute respiratory distress syndrome (ARDS), a fundamental goal is to protect the lungs from ventilation-induced injury, but the optimal PEEP level has not been established.
Study design: Systematic review and meta-analysis.
Setting: N/A.
Synopsis: Three randomized-controlled trials eligible for this review included 2,299 critically ill adults with acute lung injury, as defined by the American-European Consensus Conference. The meta-analysis compared higher and lower PEEP levels with a mean difference of at least 3 cm H2O, incorporated a target tidal volume of less than 8 mL/kg of predicted body weight in both ventilation strategies, and provided patient follow-up until death or for at least 20 days.
This review demonstrated no statistically significant difference in hospital mortality between the groups. However, in patients with ARDS, higher levels of PEEP were associated with a relative reduction in mortality of 10%. This is supported by a recent cohort study in patients with acute lung injury or ARDS, which showed that the effect of PEEP on lung recruitment was associated with the proportion of potentially recruitable lung, as determined by computed tomography.
Since patients with ARDS have more pulmonary edema than those with acute lung injury without ARDS, the former have greater recruitability, and thus might benefit more from higher levels of PEEP.
Bottom line: Higher levels of PEEP might be associated with lower hospital mortality in patients with ARDS, but such a benefit is unlikely in patients with less severe lung injuries, and could actually be harmful.
Citation: Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865-873. TH
In This Edition
Literature at a Glance
A guide to this month’s studies
- Antibiotics after drainage of uncomplicated skin abscesses
- Clopidogrel vs. combined aspirin-dipyridamole for acute ischemic stroke
- BNP-guided therapy in chronic heart failure outpatients
- Cognitive decline and dementia after hospitalization
- Clopidogrel delays up risks for DES implantation patients
- Clinical score identifies prolonged length of stay
- Time to therapy reduces mortality in sepsis patients
- PEEP associated with lower mortality for ARDS patients
Antibiotics Might Be Unnecessary after Drainage of Uncomplicated Skin Abscesses
Clinical question: Does trimethoprim/sulfamethoxazole (TMP/SMX) treatment after drainage of a skin abscess reduce treatment failure at seven days or development of new lesions at 30 days?
Background: Community ac-quired methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses are increasing in frequency. The benefit of antibiotic treatment after incision and drainage is not clear, as there is a high cure rate without antibiotics.
Study design: Multicenter, double-blinded, randomized, placebo-controlled trial.
Setting: Four military EDs treating civilians and military patients.
Synopsis: The study enrolled a convenience sample of 220 patients, each of whom presented to EDs with uncomplicated skin abscesses from November 2007 to June 2009. Abscesses were drained in the ED, then patients were randomized to either placebo or to TMP/SMX (two DS tablets twice daily) for seven days. Re-evaluation for wound checks occurred at two days and seven days.
Treatment failure at seven days, defined as worsening infection, new lesions, or absence of clinical improvement, occurred in 26% of placebo patients and 17% of patients in the treatment arm, a nonsignificant difference (P=0.12). Fewer patients in the treatment arm had new lesions at 30 days (28% vs. 9%, P=0.02). MRSA was cultured from 53% of patients overall; all samples were sensitive to TMP/SMX.
The study was limited by the fact that only 69% of patients were evaluated at 30 days.
Bottom line: TMP/SMX treatment of uncomplicated skin abscess after drainage in EDs does not decrease treatment failure at seven days, but might decrease the development of new lesions.
Citation: Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection [published online ahead of print March 29, 2010]. Ann Emerg Med. doi:10.1016/j.annemerg med.2010.03.002.
Clopidogrel and Combined Aspirin-Dipyridamole Have Similar Safety and Efficacy Profiles for Acute Ischemic Stroke
Clinical question: What is the efficacy and safety of combined aspirin and extended-release dipyridamole (Asp/ER-DP) compared to clopidogrel in patients with acute ischemic stroke?
Background: Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of Asp/ER-DP or clopidogrel is not known in patients with acute ischemic stroke.
Study design: Randomized, controlled trial.
Setting: A multicenter trial involving 695 sites in 35 countries.
Synopsis: This post-hoc subgroup analysis of the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial assessed the relative safety and efficacy of Asp/ER-DP versus clopidogrel administered within 72 hours of stroke onset in 1,360 patients. The primary endpoint was functional outcome at 30 days.
Secondary outcomes included symptomatic hemorrhagic transformation of the infarct, cerebral edema, recurrent stroke, myocardial infarction (MI), composite vascular events (combination of nonfatal stroke, nonfatal MI, and vascular death), death, cognition, bleeding, and serious adverse events studied at seven, 30, and 90 days.
Combined death or dependency did not differ between treatment groups. Nonsignificant trends to reduced recurrence and vascular events were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups.
Bottom line: Either clopidogrel or combined aspirin and extended-release dipyridamole can be used to treat acute ischemic stroke, with similar outcomes and safety profiles.
Citation: Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis. Stroke. 2010;41(4):732-738.
BNP-Guided Therapy Reduces All-Cause Mortality in Outpatients with Chronic Heart Failure
Clinical question: Is there a clinical benefit in using B-type natriuretic peptide (BNP) to guide adjustment of proven medications in chronic heart failure?
Background: BNP is secreted by the heart in response to increased volume. It has been shown to be useful in the diagnosis of decompensated heart failure, and it can be decreased by treatment with proven heart failure medications. It is unclear if this effect provides clinical benefit on mortality and hospitalization.
Study design: Meta-analysis of prospective randomized controlled trials.
Setting: Eight studies involving 1,726 patients, published internationally from 2005-2009.
Synopsis: Study sizes ranged from 41 to 499 patients, with three- to 24-month follow-up. Patients had New York Heart Association (NYHA) class II or greater heart failure, with ejection fractions <50%.
All-cause mortality was significantly lower in BNP-guided therapy compared with clinical-guided therapy (RR=0.76; 95% CI, 0.63-0.91; P=0.003), specifically in patients younger than 75 years old (RR=0.52; 95% CI, 0.33-0.82; P=0.005).
A proposed mechanism for this result was a statistically significant increase in adjustment of most heart failure medications for BNP-guided therapy compared with clinical-guided therapy (75% vs. 58%, P<0.001 in diuretics; 49.6% vs. 30.9%, P<0.001 in ACE inhibitors or Angiotensin II receptor blockers (ARBs); and 51.1% vs. 41.6%, P=0.02 in beta-blockers) and a higher percentage reaching target doses in the BNP-guided therapy group. However, there was no significant decrease in all-cause hospitalization or survival free of hospitalization.
The study limitations include: Hospitalization for heart failure was not meta-analyzed, the pooled data were weighted toward one study, and BNP-guided titration parameters varied across studies.
Bottom line: BNP-guided therapy reduces all-cause mortality in chronic heart failure patients younger than 75 years old, but not all-cause hospitalization or survival free of hospitalization.
Citation: Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med. 2010;170(6):507-514.
Hospitalization Is Associated with Cognitive Decline and Subsequent Risk for Dementia in the Elderly
Clinical question: Is critical illness in patients 65 and older associated with long-term cognitive impairment, and does it affect the incidence of dementia?
Background: There is literature suggesting that survivors of critical illness suffer long-term cognitive impairment, but premorbid measures of cognitive function have not been researched. No studies have evaluated the risk of incident dementia among this patient population.
Study design: Prospective cohort study.
Setting: Group Health Cooperative in Seattle.
Synopsis: This study analyzed data from 2,929 community-dwelling adults older than 65 without baseline dementia. From 1994 to 2007, the individuals were screened with the Cognitive Abilities Screening Instrument (CASI) at follow-up visits every two years. CASI scores lower than 86 (out of 100) led to an examination for dementia; the diagnosis of dementia was an outcome measure. Scores were adjusted for baseline cognitive scores, age, and other risk factors.
For patients following acute-care hospitalization, adjusted CASI scores were 1.01 points lower on average than for those not hospitalized. For patients following critical-illness hospitalization, scores were 2.14 points lower. The dementia rate was 14.6 cases per 1,000 person-years among patients not hospitalized, and 33.6 among those admitted for noncritical illness.
As suspected, hospitalization might be a marker for cognitive decline in the elderly after adjusting for premorbid CASI scores and comorbid illness. Some factors in acute illness—and moreso in critical illness—might be causally related to cognitive decline.
Bottom line: In elderly patients without dementia at baseline, hospitalization for acute care and critical illness increases the likelihood of cognitive decline compared with patients who were not hospitalized. Only noncritical-illness hospitalization was not associated with the development of dementia.
Citation: Ehlenbach WJ, Hough CL, Crane PK, et al. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA. 2010;303(8): 763-770.
Increased Risk of Death and Myocardial Infarction in Patients Who Delay Filling Clopidogrel Prescription after Drug-Eluting Stent Implantation
Clinical question: Is there an increased risk of death or myocardial infarction (MI) in patients with recent drug-eluting stent (DES) implantation who delayed filling their clopidogrel prescription compared with those who filled their prescription on the day of hospital discharge?
Background: Filling an initial prescription of clopidogrel on the day of discharge is important after DES implantation, as prior studies suggest that lack of thienopyridine therapy is a risk factor for early stent thrombosis.
Study design: Retrospective cohort study.
Setting: Three large, integrated healthcare systems.
Synopsis: The cohort included 7,042 patients discharged after DES implantation. Filling of a clopidogrel prescription was based on pharmacy dispensing data. Primary analysis divided patients based on whether they filled the prescription on the day of discharge or any time after discharge. Secondary analysis further characterized delays as >1 day, >3 days, or >5 days after discharge.
One in 6 patients delayed filling the initial prescription. Patients with any degree of delay had significantly higher death and MI rates during follow-up (14.2% vs. 7.9%, P<0.001), as well as an increased risk of death/MI (hazard ratio 1.53; 95% CI, 1.25-1.87). Factors associated with a delay in filling clopidogrel included older age, prior MI, diabetes, renal dysfunction, prior revascularization, cardiogenic shock, in-hospital bleeding, and use of clopidogrel upon admission.
The study was limited in that data were based on pharmacy records, and that patients might have received medication at discharge or outside the healthcare system.
Bottom line: The delay in filling a clopidogrel prescription is associated with an increased risk of death and MI in patients with recent DES implantation.
Citation: Ho PM, Tsai TT, Maddox TM, et al. Delays in filling clopidogrel prescription after hospital discharge and adverse outcomes after drug-eluting stent implantation: implications for transitions of care. Circ Cardiovasc Qual Outcomes. 2010;3(3):261-266.
Predicting Length of Stay after Stroke
Clinical question: Does a clinical score accurately predict prolonged length of stay after stroke?
Background: Stroke is a costly health problem, and length of stay is the most prominent factor contributing to the high costs. The factors leading to prolonged length of stay are varied, and there are no established tools to predict length of stay.
Study design: Prospective cohort study.
Setting: All 28 Israeli hospitals that admit stroke patients.
Synopsis: All patients admitted to Israeli hospitals during established two-month periods in 2004 (1,700 patients) and 2007 (1,648 patients) were included in the National Acute Stroke Israeli Survey (NASIS), and served as the derivation and validation cohort for development of a Prolonged Length of Stay (PLOS) score.
Using the 2004 data, investigators identified stroke severity using the National Institutes of Health Stroke Scale (NIHSS), history of congestive heart failure (CHF), history of atrial fibrillation, decreased level of consciousness on presentation, and intracerebral hemorrhage (as opposed to ischemic stroke) as predictors of prolonged length of stay. Four of these factors were expressed as dichotomous variables, whereas the stroke severity by NIHSS class was incorporated as a range; all were incorporated into a PLOS score.
Higher PLOS score correlated with longer length of stay. In the derivation cohort, 22% of patients with a PLOS score of 0 had a prolonged length of stay, whereas 85% of patients with PLOS scores of 6 or 7 had a prolonged length of stay. In the validation cohort, the corresponding figures were 19% and 72%.
Bottom line: Use of a simple score can predict risk of prolonged length of stay after stroke.
Citation: Koton S, Bornstein NM, Tsabari R, Tanne D, NASIS Investigators. Derivation and validation of the prolonged length of stay score in acute stroke patients. Neurology. 2010;74(19);1511-1516.
Earlier Administration of Appropriate Antimicrobials Decreases Mortality in Patients with Severe Sepsis and Septic Shock
Clinical question: Is the timing of antimicrobial administration an important determinant of survival in patients diagnosed with severe sepsis and septic shock?
Background: Severe sepsis and septic shock are associated with a 25% to 50% mortality rate. Early goal-directed therapy has been shown to increase survival in these patients. Antimicrobial treatment is a mainstay of this therapy, but the most effective timing of this treatment remains unclear.
Study design: Retrospective, single-center cohort study.
Setting: ED at an academic tertiary-care center.
Synopsis: Two hundred sixty-one patients in the ED in 2005-2006 presenting with severe sepsis or septic shock were enrolled in the hospital’s early goal-directed therapy (EGDT) algorithm, either at triage or later during their ED stay. Labs showed 56.7% of patients were culture-positive, with the most common sources being respiratory (30.6%), genitourinary (22.8%), and gastrointestinal (19.7%).
All patients received antibiotics and were stratified in one-hour intervals by the following categories: time from triage to antibiotics; time from qualification for EGDT to antibiotics; time from triage to appropriate antibiotics; and time from qualification for EGDT to appropriate antibiotics.
Total in-hospital mortality was 31% (35.1% for culture-positive patients vs. 25.7% for culture-negative patients, P=0.11). A significant decrease in mortality was only found when appropriate antibiotics were administered within one hour of triage, or within one hour of qualification for EGDT (OR=0.30; 95% CI, 0.11-0.83; P=0.02, and OR=0.50; 95% CI, 0.27-0.92; P=0.03, respectively).
Study limitations included the single-center site and small sample size.
Bottom line: In patients with severe sepsis and septic shock, initiating appropriate antimicrobial therapy within one hour of triage or entry into goal-directed therapy significantly reduces mortality.
Citation: Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053.
Treatment with Higher Levels of Positive End-Expiratory Pressure Has Limited Affect on Hospital Survival
Clinical question: Is treatment with higher versus lower levels of positive end-expiratory pressure (PEEP) associated with improved hospital survival?
Background: In the management of patients with acute lung injury or acute respiratory distress syndrome (ARDS), a fundamental goal is to protect the lungs from ventilation-induced injury, but the optimal PEEP level has not been established.
Study design: Systematic review and meta-analysis.
Setting: N/A.
Synopsis: Three randomized-controlled trials eligible for this review included 2,299 critically ill adults with acute lung injury, as defined by the American-European Consensus Conference. The meta-analysis compared higher and lower PEEP levels with a mean difference of at least 3 cm H2O, incorporated a target tidal volume of less than 8 mL/kg of predicted body weight in both ventilation strategies, and provided patient follow-up until death or for at least 20 days.
This review demonstrated no statistically significant difference in hospital mortality between the groups. However, in patients with ARDS, higher levels of PEEP were associated with a relative reduction in mortality of 10%. This is supported by a recent cohort study in patients with acute lung injury or ARDS, which showed that the effect of PEEP on lung recruitment was associated with the proportion of potentially recruitable lung, as determined by computed tomography.
Since patients with ARDS have more pulmonary edema than those with acute lung injury without ARDS, the former have greater recruitability, and thus might benefit more from higher levels of PEEP.
Bottom line: Higher levels of PEEP might be associated with lower hospital mortality in patients with ARDS, but such a benefit is unlikely in patients with less severe lung injuries, and could actually be harmful.
Citation: Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865-873. TH
In the Literature
In This Edition
- Pharmacists and readmission rates.
- Geriatric discharge bundles and readmission rates.
- Medication reconciliation and risk of adverse drug events.
- End-of-life discussions and care outcomes.
- Effect of case management and housing for homeless adults.
- IV esomeprazole in bleeding ulcers.
- Causes of discharge delays.
- Methods to reduce ICU medication errors.
Addition of Pharmacists to Inpatient Teams Reduces Drug-Related Readmissions, Morbidity, and Costs for Elderly Patients
Clinical question: Would a ward-based pharmacist reduce morbidity, subsequent ED visits, and readmissions for elderly patients?
Background: Adverse drug events can cause significant drug-related morbidity and mortality, and lead to unnecessary healthcare costs. Elderly patients are more vulnerable to these effects given the polypharmacy often associated with their care. The effectiveness of a ward-based pharmacist intervention for elderly patients has not yet been studied.
Study design: Randomized controlled trial.
Setting: Two acute-care, internal-medicine wards at the University Hospital of Uppsala in Uppsala, Sweden.
Synopsis: Three hundred sixty-eight hospitalized patients ages 80 or older were randomized to control or intervention groups. The latter received enhanced services from a pharmacist who was integrated into the inpatient team. This individual performed medication reconciliation, reviewed the medication list, and advised the treating physician. The pharmacist educated and monitored patients during the hospitalization, counseled them at discharge, communicated pertinent medication information to the primary-care physicians (PCPs), and called the patients two months after discharge.
The primary outcome measure was the frequency of all hospital visits (ED visits plus hospital readmissions) during 12-month follow-up. The secondary outcome measure was the cost of hospital care.
The intervention group had a 16% reduction in all hospital visits and a 47% reduction in ED visits. There were five times as many drug-related readmissions in the control group compared with the intervention group, but the study did not have enough power to show a reduction in the total number of readmissions alone. The cost of hospital care minus the cost of the intervention resulted in a net savings of $230 per patient.
Bottom line: For elderly patients, adding a pharmacist to the inpatient team could lead to significant reductions in morbidity and, on a population basis, healthcare costs.
Citation: Gillespie U, Alassaad A, Henrohn D, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial. Arch Intern Med. 2009;169(9):894-900.
Geriatric Care Coordination at Discharge Reduces Readmission Rates at 30 Days
Clinical question: Does a discharge planning service package affect readmission rates and ED visits?
Background: Elderly patients are at high risk for readmission after a hospitalization. Coordinated care packages, although effective in congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) management, have yielded inconsistent results in terms of decreasing readmission rates for patients with a broader range of medical issues.
Study design: Randomized controlled pilot study.
Setting: A single large academic medical center in Texas.
Synopsis: Forty-one elderly patients at high risk for readmission—because of their age and comorbidities—were enrolled within 72 hours of admission. Patients randomized to the care bundle arm received daily education about medication reconciliation, health conditions, and self-care provided by study pharmacists and nurses. The intervention required approximately 40 minutes per day: 20 to 25 minutes for the care coordinators and 20 minutes for the pharmacists. A post-discharge phone call to review medication and confirm follow-up instructions was included.
Eight patients in the control group and two patients in the intervention arm were readmitted or seen in the ED within 30 days after discharge (38% vs. 10%, P=0.004). At 60 days, the difference between the two groups was no longer significant. The intervention group had a longer time interval before its first readmission (36.2 days vs. 15.7 days). The sample was too small to determine the effect on length of hospitalization.
Limitations of the study include its small sample size and unclear costs of the intervention.
Bottom line: Geriatric discharge bundles might decrease readmission and ED visits after discharge, but larger studies are needed to confirm this finding.
Citation: Koehler BE, Richter KM, Youngblood L, et al. Reduction of 30-day post-discharge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.
Computer-Assisted Medication Reconciliation Might Reduce Unintentional Drug Discrepancies with Potential for Harm
Clinical question: Does a computerized medication reconciliation intervention reduce unintentional medication discrepancies?
Background: Given the high prevalence of unintentional medication discrepancies in hospitalized patients and the potential for harm, medication reconciliation is a national patient safety goal. Little data exist on the efficacy of medication reconciliation interventions for reducing medication discrepancies.
Study design: Cluster-randomized controlled trial.
Setting: Two large academic hospitals in Boston.
Synopsis: Using 14 medical teams, the study enrolled and randomized 322 patients to a floor with intervention or to a floor with traditional care. The intervention teams utilized a computerized order entry application designed to facilitate medication reconciliation, as well as a process redesign for physicians, nurses, and pharmacists.
The primary outcome was the number of unintentional medication discrepancies with the potential for causing harm (PADEs) per patient.
Patients randomized to the intervention group had a 28% reduction in relative risk compared with the control group (1.05 PADEs vs. 1.44 PADEs; absolute relative risk 0.72 (0.52-0.99)). The absolute relative risk reduction between the two arms was 0.39 PADE per patient (NNT=2.6). The intervention was associated with a significant reduction in PADEs at discharge but not at admission. The effects of the intervention were greater in patients with a higher PADE score.
Bottom line: This computerized medication reconciliation program with process redesign was associated with reduced risk of unintentional medication discrepancies with potential for causing harms (PADEs).
Citation: Schnipper JL, Hamann C, Ndumele CD, et al. Effect of an electronic medication reconciliation application and process redesign on potential adverse drug events: a cluster-randomized trial. Arch Intern Med. 2009;169(8):771-780.
End-of-Life Discussions Associated with Lower Healthcare Costs
Clinical question: What is the impact of patient-physician discussions of end-of-life care on healthcare costs in the final week of a patient’s life?
Background: Life-sustaining medical care of patients with advanced cancer is costly, with disproportionate spending at the end of a patient’s life. The link between discussions of end-of-life care preferences and healthcare expenditure has not been studied thoroughly.
Study design: Prospective observational study.
Setting: Seven sites in Connecticut, Texas, New Hampshire, and Massachusetts.
Synopsis: More than 600 patients with advanced cancer were recruited from September 2002 through December 2007 as part of the Coping With Cancer study. The 188 patients (31%) who reported end-of-life discussions with their physicians at baseline were less likely to undergo mechanical ventilator use or resuscitation, or to be admitted or die in an intensive-care unit in the final week of life. They were more likely to receive outpatient hospice care and had less physical distress in the last week than those who did not.
The mean aggregate cost of care in this group was $1,876, which was 36% lower than in the group that did not discuss end-of-life care ($2,917), P=0.002. In addition, higher medical costs were associated with worse quality of death, as reported by caregivers.
This study is limited by its observational design.
Bottom line: Physician communication with patients regarding end-of-life care preferences is associated with lower costs in the final week of life.
Citation: Zhang B, Wright AA, Huskamp HA, et al. Health care costs in the last week of life: associations with end-of-life conversations. Arch Intern Med. 2009;169(5):480-488.
Reduction of ED Visits and Hospitalizations for Chronically Ill and Homeless Adults
Clinical question: Can a case management and housing program reduce the utilization of ED and hospital medical services among chronically ill homeless adults?
Background: Homeless adults have high rates of chronic illness, have poor access to uninterrupted primary healthcare, and frequently use costly medical services, including those provided by EDs and inpatient hospitalizations. Studies to determine the efficacy of housing and case management services in reducing hospital and ED utilization in this population are lacking.
Study design: Randomized controlled trial.
Setting: A public teaching hospital and a private nonprofit hospital in Chicago.
Synopsis: Four hundred seven chronically ill and homeless adults were randomized to receive a case management and housing intervention or traditional care following an index hospitalization. The intervention group received assistance with stable housing on discharge and biweekly case management services throughout the study period. Traditional care consisted of routine inpatient discharge planning and transportation to a shelter.
Patients were followed for 18 months for the primary outcomes: number of hospitalizations, total hospital days, and number of ED visits.
After adjusting for differences in baseline variables, the intervention group was found to have significantly lower rates of hospitalization (relative reduction 29%), total hospital days (29%), and ED visits (24%). The authors did not find a difference in mortality or quality of life between the two groups.
Limitations of this study include a small sample size, limited geographic distribution of subjects, and the lack of a cost-benefit analysis of the intervention.
Bottom line: Case management and housing interventions can decrease hospitalizations and ED visits among chronically ill homeless adults.
Citation: Sadowski LS, Kee RA, VanderWeele TJ, Buchanan D. Effect of a housing and case management program on emergency department visits and hospitalizations among chronically ill homeless adults: a randomized trial. JAMA. 2009;301(17):1771-1778.
Intravenous Esomeprazole Reduces Recurrent Bleeding from Peptic Ulcers
Clinical question: Does intravenous esomeprazole prevent recurrent peptic ulcer bleeding, compared with placebo?
Background: U.S. hospitals admit more than 300,000 patients per year for peptic ulcer bleeding. Asian studies of proton pump inhibitors have demonstrated improved outcomes in patients with bleeding caused by peptic ulcers, but these results have not been consistently replicated in studies in Western Europe or North America.
Study design: Randomized, placebo-controlled, double-blind trial.
Setting: Ninety-one hospital EDs in 16 countries.
Synopsis: The study team randomized 764 adult patients with a single bleeding gastric or duodenal ulcer after successful endoscopic hemostasis. The study group received esomeprazole (80 mg bolus, given intravenously over 30 minutes, followed by an 8 mg/hour infusion for 71.5 hours). The second group received placebo. Each group subsequently received 40 mg/day of oral esomeprazole for 27 days.
Recurrent bleeding within 72 hours was reduced by nearly half in the intravenous esomeprazole arm compared with placebo (5.9% vs. 10.3%, P=0.026). This remained significant at seven and 30 days. Intravenous esomeprazole also reduced endoscopic retreatment (6.4% vs. 11.6%; P=0.012) and demonstrated a trend toward reduction in surgery (2.7% vs. 5.4%) and all-cause mortality (0.8% vs. 2.1%).
Study limitations included a lack of standardization of endoscopic therapy across institutions.
Bottom line: Given after endoscopic hemostatis, intravenous esomeprazole followed by oral esomeprazole reduced recurrent bleeding in patients with a single duodenal or gastric ulcer.
Citation: Sung JJ, Barkun A, Kuipers EJ, et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2009;150(7):455-464.
Discharge Time and Duration Affected by Several Factors During Hospitalization
Clinical question: What are the factors affecting late and long discharges in a general medical unit?
Background: The mismatch between admission and discharge times is a problem for many hospitals; admissions occur early in the day whereas, discharges occur later in the day. The reasons behind delays in discharge and prolongation of discharges are not fully understood.
Study design: Prospective cohort study.
Setting: A general medical unit without house staff coverage at an academic medical center in Baltimore.
Synopsis: Care providers completed surveys on 201 consecutive discharges from January to April 2005. Outcome variables included time of discharge and discharge duration.
Mean discharge time was 3:09 p.m. Delay in discharge was associated with a need for ambulance transportation (1.5 hours), need for prescriptions to be filled at the hospital (1.4 hours), and for patients whose final test was a procedure (1.2 hours) or consult (1.1 hours).
Median discharge time was 7.6 hours. Longer discharge duration was associated with discharge to a location other than home (28.9 hours), need for consultation (14.8 hours), or need for a procedure (13.4 hours) before discharge.
African-American race, gender, age, and comorbid psychiatric and substance abuse disorders were not associated with either late or prolonged discharges.
Bottom line: Final-day tests, procedures, and consults, as well as complex discharge arrangements, prolong and delay discharges more than the characteristics of patients themselves.
Citation: Chen LM, Freitag MH, Franco M, Sullivan CD, Dickson C, Brancati FL. Natural history of late discharges from a general medical ward. J Hosp Med. 2009;4(4):226-233.
Administration of Parenteral Medication a Common Point at Which Errors Occur in ICUs
Clinical question: To what extent are medication administration errors a problem across ICUs, and what are some ways to prevent them?
Background: High-acuity and complex systems increase the likelihood of medical errors in ICUs. The first multinational Sentinel Events Evaluation study reported an ICU medication error rate of 10.5 per 100 patient days at the prescription and administration stages of medication delivery.
Study design: Multinational observational, prospective, cross-sectional study.
Setting: One hundred thirteen ICUs in 27 countries on five continents.
Synopsis: This study addressed five types of medication error at the administration stage in the ICU in a 24-hour timeframe: wrong drug, wrong dose, wrong route, wrong time, and missed medication. The main outcome measures were the number and impact of administration errors, the distribution of error characteristics, and the distribution of contributing and preventive factors.
In the 1,328 critically ill patients included in the study, 861 medication errors were reported by structured questionnaire; 441 patients were affected by the errors. The prevalence was 74.5 errors per 100 patient days, and 12 patients (0.9%) suffered permanent harm or death. Most medication administration errors occurred during routine care, not during extraordinary situations. Most were omission errors.
This study is limited by its observational design and by the fact that self-reporting also carries the risk of under-reporting.
This study points out several ways to reduce medication errors. An independent predictor of decreased risk of medication errors of all types is an established incident reporting system. Routine checking of infusion pumps at every nursing shift change also reduced this risk.
Bottom line: This study confirmed that the administration of parenteral medications is a vulnerable point across many ICUs, and incident reporting systems and routine checks of infusion pumps are effective ways to reduce the risk of this type of error.
Citation: Valentin A, Capuzzo M, Guidet B, et al. Errors in administration of parenteral drugs in intensive care units: multinational prospective study. BMJ. 2009;338:b814. TH
In This Edition
- Pharmacists and readmission rates.
- Geriatric discharge bundles and readmission rates.
- Medication reconciliation and risk of adverse drug events.
- End-of-life discussions and care outcomes.
- Effect of case management and housing for homeless adults.
- IV esomeprazole in bleeding ulcers.
- Causes of discharge delays.
- Methods to reduce ICU medication errors.
Addition of Pharmacists to Inpatient Teams Reduces Drug-Related Readmissions, Morbidity, and Costs for Elderly Patients
Clinical question: Would a ward-based pharmacist reduce morbidity, subsequent ED visits, and readmissions for elderly patients?
Background: Adverse drug events can cause significant drug-related morbidity and mortality, and lead to unnecessary healthcare costs. Elderly patients are more vulnerable to these effects given the polypharmacy often associated with their care. The effectiveness of a ward-based pharmacist intervention for elderly patients has not yet been studied.
Study design: Randomized controlled trial.
Setting: Two acute-care, internal-medicine wards at the University Hospital of Uppsala in Uppsala, Sweden.
Synopsis: Three hundred sixty-eight hospitalized patients ages 80 or older were randomized to control or intervention groups. The latter received enhanced services from a pharmacist who was integrated into the inpatient team. This individual performed medication reconciliation, reviewed the medication list, and advised the treating physician. The pharmacist educated and monitored patients during the hospitalization, counseled them at discharge, communicated pertinent medication information to the primary-care physicians (PCPs), and called the patients two months after discharge.
The primary outcome measure was the frequency of all hospital visits (ED visits plus hospital readmissions) during 12-month follow-up. The secondary outcome measure was the cost of hospital care.
The intervention group had a 16% reduction in all hospital visits and a 47% reduction in ED visits. There were five times as many drug-related readmissions in the control group compared with the intervention group, but the study did not have enough power to show a reduction in the total number of readmissions alone. The cost of hospital care minus the cost of the intervention resulted in a net savings of $230 per patient.
Bottom line: For elderly patients, adding a pharmacist to the inpatient team could lead to significant reductions in morbidity and, on a population basis, healthcare costs.
Citation: Gillespie U, Alassaad A, Henrohn D, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial. Arch Intern Med. 2009;169(9):894-900.
Geriatric Care Coordination at Discharge Reduces Readmission Rates at 30 Days
Clinical question: Does a discharge planning service package affect readmission rates and ED visits?
Background: Elderly patients are at high risk for readmission after a hospitalization. Coordinated care packages, although effective in congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) management, have yielded inconsistent results in terms of decreasing readmission rates for patients with a broader range of medical issues.
Study design: Randomized controlled pilot study.
Setting: A single large academic medical center in Texas.
Synopsis: Forty-one elderly patients at high risk for readmission—because of their age and comorbidities—were enrolled within 72 hours of admission. Patients randomized to the care bundle arm received daily education about medication reconciliation, health conditions, and self-care provided by study pharmacists and nurses. The intervention required approximately 40 minutes per day: 20 to 25 minutes for the care coordinators and 20 minutes for the pharmacists. A post-discharge phone call to review medication and confirm follow-up instructions was included.
Eight patients in the control group and two patients in the intervention arm were readmitted or seen in the ED within 30 days after discharge (38% vs. 10%, P=0.004). At 60 days, the difference between the two groups was no longer significant. The intervention group had a longer time interval before its first readmission (36.2 days vs. 15.7 days). The sample was too small to determine the effect on length of hospitalization.
Limitations of the study include its small sample size and unclear costs of the intervention.
Bottom line: Geriatric discharge bundles might decrease readmission and ED visits after discharge, but larger studies are needed to confirm this finding.
Citation: Koehler BE, Richter KM, Youngblood L, et al. Reduction of 30-day post-discharge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.
Computer-Assisted Medication Reconciliation Might Reduce Unintentional Drug Discrepancies with Potential for Harm
Clinical question: Does a computerized medication reconciliation intervention reduce unintentional medication discrepancies?
Background: Given the high prevalence of unintentional medication discrepancies in hospitalized patients and the potential for harm, medication reconciliation is a national patient safety goal. Little data exist on the efficacy of medication reconciliation interventions for reducing medication discrepancies.
Study design: Cluster-randomized controlled trial.
Setting: Two large academic hospitals in Boston.
Synopsis: Using 14 medical teams, the study enrolled and randomized 322 patients to a floor with intervention or to a floor with traditional care. The intervention teams utilized a computerized order entry application designed to facilitate medication reconciliation, as well as a process redesign for physicians, nurses, and pharmacists.
The primary outcome was the number of unintentional medication discrepancies with the potential for causing harm (PADEs) per patient.
Patients randomized to the intervention group had a 28% reduction in relative risk compared with the control group (1.05 PADEs vs. 1.44 PADEs; absolute relative risk 0.72 (0.52-0.99)). The absolute relative risk reduction between the two arms was 0.39 PADE per patient (NNT=2.6). The intervention was associated with a significant reduction in PADEs at discharge but not at admission. The effects of the intervention were greater in patients with a higher PADE score.
Bottom line: This computerized medication reconciliation program with process redesign was associated with reduced risk of unintentional medication discrepancies with potential for causing harms (PADEs).
Citation: Schnipper JL, Hamann C, Ndumele CD, et al. Effect of an electronic medication reconciliation application and process redesign on potential adverse drug events: a cluster-randomized trial. Arch Intern Med. 2009;169(8):771-780.
End-of-Life Discussions Associated with Lower Healthcare Costs
Clinical question: What is the impact of patient-physician discussions of end-of-life care on healthcare costs in the final week of a patient’s life?
Background: Life-sustaining medical care of patients with advanced cancer is costly, with disproportionate spending at the end of a patient’s life. The link between discussions of end-of-life care preferences and healthcare expenditure has not been studied thoroughly.
Study design: Prospective observational study.
Setting: Seven sites in Connecticut, Texas, New Hampshire, and Massachusetts.
Synopsis: More than 600 patients with advanced cancer were recruited from September 2002 through December 2007 as part of the Coping With Cancer study. The 188 patients (31%) who reported end-of-life discussions with their physicians at baseline were less likely to undergo mechanical ventilator use or resuscitation, or to be admitted or die in an intensive-care unit in the final week of life. They were more likely to receive outpatient hospice care and had less physical distress in the last week than those who did not.
The mean aggregate cost of care in this group was $1,876, which was 36% lower than in the group that did not discuss end-of-life care ($2,917), P=0.002. In addition, higher medical costs were associated with worse quality of death, as reported by caregivers.
This study is limited by its observational design.
Bottom line: Physician communication with patients regarding end-of-life care preferences is associated with lower costs in the final week of life.
Citation: Zhang B, Wright AA, Huskamp HA, et al. Health care costs in the last week of life: associations with end-of-life conversations. Arch Intern Med. 2009;169(5):480-488.
Reduction of ED Visits and Hospitalizations for Chronically Ill and Homeless Adults
Clinical question: Can a case management and housing program reduce the utilization of ED and hospital medical services among chronically ill homeless adults?
Background: Homeless adults have high rates of chronic illness, have poor access to uninterrupted primary healthcare, and frequently use costly medical services, including those provided by EDs and inpatient hospitalizations. Studies to determine the efficacy of housing and case management services in reducing hospital and ED utilization in this population are lacking.
Study design: Randomized controlled trial.
Setting: A public teaching hospital and a private nonprofit hospital in Chicago.
Synopsis: Four hundred seven chronically ill and homeless adults were randomized to receive a case management and housing intervention or traditional care following an index hospitalization. The intervention group received assistance with stable housing on discharge and biweekly case management services throughout the study period. Traditional care consisted of routine inpatient discharge planning and transportation to a shelter.
Patients were followed for 18 months for the primary outcomes: number of hospitalizations, total hospital days, and number of ED visits.
After adjusting for differences in baseline variables, the intervention group was found to have significantly lower rates of hospitalization (relative reduction 29%), total hospital days (29%), and ED visits (24%). The authors did not find a difference in mortality or quality of life between the two groups.
Limitations of this study include a small sample size, limited geographic distribution of subjects, and the lack of a cost-benefit analysis of the intervention.
Bottom line: Case management and housing interventions can decrease hospitalizations and ED visits among chronically ill homeless adults.
Citation: Sadowski LS, Kee RA, VanderWeele TJ, Buchanan D. Effect of a housing and case management program on emergency department visits and hospitalizations among chronically ill homeless adults: a randomized trial. JAMA. 2009;301(17):1771-1778.
Intravenous Esomeprazole Reduces Recurrent Bleeding from Peptic Ulcers
Clinical question: Does intravenous esomeprazole prevent recurrent peptic ulcer bleeding, compared with placebo?
Background: U.S. hospitals admit more than 300,000 patients per year for peptic ulcer bleeding. Asian studies of proton pump inhibitors have demonstrated improved outcomes in patients with bleeding caused by peptic ulcers, but these results have not been consistently replicated in studies in Western Europe or North America.
Study design: Randomized, placebo-controlled, double-blind trial.
Setting: Ninety-one hospital EDs in 16 countries.
Synopsis: The study team randomized 764 adult patients with a single bleeding gastric or duodenal ulcer after successful endoscopic hemostasis. The study group received esomeprazole (80 mg bolus, given intravenously over 30 minutes, followed by an 8 mg/hour infusion for 71.5 hours). The second group received placebo. Each group subsequently received 40 mg/day of oral esomeprazole for 27 days.
Recurrent bleeding within 72 hours was reduced by nearly half in the intravenous esomeprazole arm compared with placebo (5.9% vs. 10.3%, P=0.026). This remained significant at seven and 30 days. Intravenous esomeprazole also reduced endoscopic retreatment (6.4% vs. 11.6%; P=0.012) and demonstrated a trend toward reduction in surgery (2.7% vs. 5.4%) and all-cause mortality (0.8% vs. 2.1%).
Study limitations included a lack of standardization of endoscopic therapy across institutions.
Bottom line: Given after endoscopic hemostatis, intravenous esomeprazole followed by oral esomeprazole reduced recurrent bleeding in patients with a single duodenal or gastric ulcer.
Citation: Sung JJ, Barkun A, Kuipers EJ, et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2009;150(7):455-464.
Discharge Time and Duration Affected by Several Factors During Hospitalization
Clinical question: What are the factors affecting late and long discharges in a general medical unit?
Background: The mismatch between admission and discharge times is a problem for many hospitals; admissions occur early in the day whereas, discharges occur later in the day. The reasons behind delays in discharge and prolongation of discharges are not fully understood.
Study design: Prospective cohort study.
Setting: A general medical unit without house staff coverage at an academic medical center in Baltimore.
Synopsis: Care providers completed surveys on 201 consecutive discharges from January to April 2005. Outcome variables included time of discharge and discharge duration.
Mean discharge time was 3:09 p.m. Delay in discharge was associated with a need for ambulance transportation (1.5 hours), need for prescriptions to be filled at the hospital (1.4 hours), and for patients whose final test was a procedure (1.2 hours) or consult (1.1 hours).
Median discharge time was 7.6 hours. Longer discharge duration was associated with discharge to a location other than home (28.9 hours), need for consultation (14.8 hours), or need for a procedure (13.4 hours) before discharge.
African-American race, gender, age, and comorbid psychiatric and substance abuse disorders were not associated with either late or prolonged discharges.
Bottom line: Final-day tests, procedures, and consults, as well as complex discharge arrangements, prolong and delay discharges more than the characteristics of patients themselves.
Citation: Chen LM, Freitag MH, Franco M, Sullivan CD, Dickson C, Brancati FL. Natural history of late discharges from a general medical ward. J Hosp Med. 2009;4(4):226-233.
Administration of Parenteral Medication a Common Point at Which Errors Occur in ICUs
Clinical question: To what extent are medication administration errors a problem across ICUs, and what are some ways to prevent them?
Background: High-acuity and complex systems increase the likelihood of medical errors in ICUs. The first multinational Sentinel Events Evaluation study reported an ICU medication error rate of 10.5 per 100 patient days at the prescription and administration stages of medication delivery.
Study design: Multinational observational, prospective, cross-sectional study.
Setting: One hundred thirteen ICUs in 27 countries on five continents.
Synopsis: This study addressed five types of medication error at the administration stage in the ICU in a 24-hour timeframe: wrong drug, wrong dose, wrong route, wrong time, and missed medication. The main outcome measures were the number and impact of administration errors, the distribution of error characteristics, and the distribution of contributing and preventive factors.
In the 1,328 critically ill patients included in the study, 861 medication errors were reported by structured questionnaire; 441 patients were affected by the errors. The prevalence was 74.5 errors per 100 patient days, and 12 patients (0.9%) suffered permanent harm or death. Most medication administration errors occurred during routine care, not during extraordinary situations. Most were omission errors.
This study is limited by its observational design and by the fact that self-reporting also carries the risk of under-reporting.
This study points out several ways to reduce medication errors. An independent predictor of decreased risk of medication errors of all types is an established incident reporting system. Routine checking of infusion pumps at every nursing shift change also reduced this risk.
Bottom line: This study confirmed that the administration of parenteral medications is a vulnerable point across many ICUs, and incident reporting systems and routine checks of infusion pumps are effective ways to reduce the risk of this type of error.
Citation: Valentin A, Capuzzo M, Guidet B, et al. Errors in administration of parenteral drugs in intensive care units: multinational prospective study. BMJ. 2009;338:b814. TH
In This Edition
- Pharmacists and readmission rates.
- Geriatric discharge bundles and readmission rates.
- Medication reconciliation and risk of adverse drug events.
- End-of-life discussions and care outcomes.
- Effect of case management and housing for homeless adults.
- IV esomeprazole in bleeding ulcers.
- Causes of discharge delays.
- Methods to reduce ICU medication errors.
Addition of Pharmacists to Inpatient Teams Reduces Drug-Related Readmissions, Morbidity, and Costs for Elderly Patients
Clinical question: Would a ward-based pharmacist reduce morbidity, subsequent ED visits, and readmissions for elderly patients?
Background: Adverse drug events can cause significant drug-related morbidity and mortality, and lead to unnecessary healthcare costs. Elderly patients are more vulnerable to these effects given the polypharmacy often associated with their care. The effectiveness of a ward-based pharmacist intervention for elderly patients has not yet been studied.
Study design: Randomized controlled trial.
Setting: Two acute-care, internal-medicine wards at the University Hospital of Uppsala in Uppsala, Sweden.
Synopsis: Three hundred sixty-eight hospitalized patients ages 80 or older were randomized to control or intervention groups. The latter received enhanced services from a pharmacist who was integrated into the inpatient team. This individual performed medication reconciliation, reviewed the medication list, and advised the treating physician. The pharmacist educated and monitored patients during the hospitalization, counseled them at discharge, communicated pertinent medication information to the primary-care physicians (PCPs), and called the patients two months after discharge.
The primary outcome measure was the frequency of all hospital visits (ED visits plus hospital readmissions) during 12-month follow-up. The secondary outcome measure was the cost of hospital care.
The intervention group had a 16% reduction in all hospital visits and a 47% reduction in ED visits. There were five times as many drug-related readmissions in the control group compared with the intervention group, but the study did not have enough power to show a reduction in the total number of readmissions alone. The cost of hospital care minus the cost of the intervention resulted in a net savings of $230 per patient.
Bottom line: For elderly patients, adding a pharmacist to the inpatient team could lead to significant reductions in morbidity and, on a population basis, healthcare costs.
Citation: Gillespie U, Alassaad A, Henrohn D, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial. Arch Intern Med. 2009;169(9):894-900.
Geriatric Care Coordination at Discharge Reduces Readmission Rates at 30 Days
Clinical question: Does a discharge planning service package affect readmission rates and ED visits?
Background: Elderly patients are at high risk for readmission after a hospitalization. Coordinated care packages, although effective in congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) management, have yielded inconsistent results in terms of decreasing readmission rates for patients with a broader range of medical issues.
Study design: Randomized controlled pilot study.
Setting: A single large academic medical center in Texas.
Synopsis: Forty-one elderly patients at high risk for readmission—because of their age and comorbidities—were enrolled within 72 hours of admission. Patients randomized to the care bundle arm received daily education about medication reconciliation, health conditions, and self-care provided by study pharmacists and nurses. The intervention required approximately 40 minutes per day: 20 to 25 minutes for the care coordinators and 20 minutes for the pharmacists. A post-discharge phone call to review medication and confirm follow-up instructions was included.
Eight patients in the control group and two patients in the intervention arm were readmitted or seen in the ED within 30 days after discharge (38% vs. 10%, P=0.004). At 60 days, the difference between the two groups was no longer significant. The intervention group had a longer time interval before its first readmission (36.2 days vs. 15.7 days). The sample was too small to determine the effect on length of hospitalization.
Limitations of the study include its small sample size and unclear costs of the intervention.
Bottom line: Geriatric discharge bundles might decrease readmission and ED visits after discharge, but larger studies are needed to confirm this finding.
Citation: Koehler BE, Richter KM, Youngblood L, et al. Reduction of 30-day post-discharge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.
Computer-Assisted Medication Reconciliation Might Reduce Unintentional Drug Discrepancies with Potential for Harm
Clinical question: Does a computerized medication reconciliation intervention reduce unintentional medication discrepancies?
Background: Given the high prevalence of unintentional medication discrepancies in hospitalized patients and the potential for harm, medication reconciliation is a national patient safety goal. Little data exist on the efficacy of medication reconciliation interventions for reducing medication discrepancies.
Study design: Cluster-randomized controlled trial.
Setting: Two large academic hospitals in Boston.
Synopsis: Using 14 medical teams, the study enrolled and randomized 322 patients to a floor with intervention or to a floor with traditional care. The intervention teams utilized a computerized order entry application designed to facilitate medication reconciliation, as well as a process redesign for physicians, nurses, and pharmacists.
The primary outcome was the number of unintentional medication discrepancies with the potential for causing harm (PADEs) per patient.
Patients randomized to the intervention group had a 28% reduction in relative risk compared with the control group (1.05 PADEs vs. 1.44 PADEs; absolute relative risk 0.72 (0.52-0.99)). The absolute relative risk reduction between the two arms was 0.39 PADE per patient (NNT=2.6). The intervention was associated with a significant reduction in PADEs at discharge but not at admission. The effects of the intervention were greater in patients with a higher PADE score.
Bottom line: This computerized medication reconciliation program with process redesign was associated with reduced risk of unintentional medication discrepancies with potential for causing harms (PADEs).
Citation: Schnipper JL, Hamann C, Ndumele CD, et al. Effect of an electronic medication reconciliation application and process redesign on potential adverse drug events: a cluster-randomized trial. Arch Intern Med. 2009;169(8):771-780.
End-of-Life Discussions Associated with Lower Healthcare Costs
Clinical question: What is the impact of patient-physician discussions of end-of-life care on healthcare costs in the final week of a patient’s life?
Background: Life-sustaining medical care of patients with advanced cancer is costly, with disproportionate spending at the end of a patient’s life. The link between discussions of end-of-life care preferences and healthcare expenditure has not been studied thoroughly.
Study design: Prospective observational study.
Setting: Seven sites in Connecticut, Texas, New Hampshire, and Massachusetts.
Synopsis: More than 600 patients with advanced cancer were recruited from September 2002 through December 2007 as part of the Coping With Cancer study. The 188 patients (31%) who reported end-of-life discussions with their physicians at baseline were less likely to undergo mechanical ventilator use or resuscitation, or to be admitted or die in an intensive-care unit in the final week of life. They were more likely to receive outpatient hospice care and had less physical distress in the last week than those who did not.
The mean aggregate cost of care in this group was $1,876, which was 36% lower than in the group that did not discuss end-of-life care ($2,917), P=0.002. In addition, higher medical costs were associated with worse quality of death, as reported by caregivers.
This study is limited by its observational design.
Bottom line: Physician communication with patients regarding end-of-life care preferences is associated with lower costs in the final week of life.
Citation: Zhang B, Wright AA, Huskamp HA, et al. Health care costs in the last week of life: associations with end-of-life conversations. Arch Intern Med. 2009;169(5):480-488.
Reduction of ED Visits and Hospitalizations for Chronically Ill and Homeless Adults
Clinical question: Can a case management and housing program reduce the utilization of ED and hospital medical services among chronically ill homeless adults?
Background: Homeless adults have high rates of chronic illness, have poor access to uninterrupted primary healthcare, and frequently use costly medical services, including those provided by EDs and inpatient hospitalizations. Studies to determine the efficacy of housing and case management services in reducing hospital and ED utilization in this population are lacking.
Study design: Randomized controlled trial.
Setting: A public teaching hospital and a private nonprofit hospital in Chicago.
Synopsis: Four hundred seven chronically ill and homeless adults were randomized to receive a case management and housing intervention or traditional care following an index hospitalization. The intervention group received assistance with stable housing on discharge and biweekly case management services throughout the study period. Traditional care consisted of routine inpatient discharge planning and transportation to a shelter.
Patients were followed for 18 months for the primary outcomes: number of hospitalizations, total hospital days, and number of ED visits.
After adjusting for differences in baseline variables, the intervention group was found to have significantly lower rates of hospitalization (relative reduction 29%), total hospital days (29%), and ED visits (24%). The authors did not find a difference in mortality or quality of life between the two groups.
Limitations of this study include a small sample size, limited geographic distribution of subjects, and the lack of a cost-benefit analysis of the intervention.
Bottom line: Case management and housing interventions can decrease hospitalizations and ED visits among chronically ill homeless adults.
Citation: Sadowski LS, Kee RA, VanderWeele TJ, Buchanan D. Effect of a housing and case management program on emergency department visits and hospitalizations among chronically ill homeless adults: a randomized trial. JAMA. 2009;301(17):1771-1778.
Intravenous Esomeprazole Reduces Recurrent Bleeding from Peptic Ulcers
Clinical question: Does intravenous esomeprazole prevent recurrent peptic ulcer bleeding, compared with placebo?
Background: U.S. hospitals admit more than 300,000 patients per year for peptic ulcer bleeding. Asian studies of proton pump inhibitors have demonstrated improved outcomes in patients with bleeding caused by peptic ulcers, but these results have not been consistently replicated in studies in Western Europe or North America.
Study design: Randomized, placebo-controlled, double-blind trial.
Setting: Ninety-one hospital EDs in 16 countries.
Synopsis: The study team randomized 764 adult patients with a single bleeding gastric or duodenal ulcer after successful endoscopic hemostasis. The study group received esomeprazole (80 mg bolus, given intravenously over 30 minutes, followed by an 8 mg/hour infusion for 71.5 hours). The second group received placebo. Each group subsequently received 40 mg/day of oral esomeprazole for 27 days.
Recurrent bleeding within 72 hours was reduced by nearly half in the intravenous esomeprazole arm compared with placebo (5.9% vs. 10.3%, P=0.026). This remained significant at seven and 30 days. Intravenous esomeprazole also reduced endoscopic retreatment (6.4% vs. 11.6%; P=0.012) and demonstrated a trend toward reduction in surgery (2.7% vs. 5.4%) and all-cause mortality (0.8% vs. 2.1%).
Study limitations included a lack of standardization of endoscopic therapy across institutions.
Bottom line: Given after endoscopic hemostatis, intravenous esomeprazole followed by oral esomeprazole reduced recurrent bleeding in patients with a single duodenal or gastric ulcer.
Citation: Sung JJ, Barkun A, Kuipers EJ, et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2009;150(7):455-464.
Discharge Time and Duration Affected by Several Factors During Hospitalization
Clinical question: What are the factors affecting late and long discharges in a general medical unit?
Background: The mismatch between admission and discharge times is a problem for many hospitals; admissions occur early in the day whereas, discharges occur later in the day. The reasons behind delays in discharge and prolongation of discharges are not fully understood.
Study design: Prospective cohort study.
Setting: A general medical unit without house staff coverage at an academic medical center in Baltimore.
Synopsis: Care providers completed surveys on 201 consecutive discharges from January to April 2005. Outcome variables included time of discharge and discharge duration.
Mean discharge time was 3:09 p.m. Delay in discharge was associated with a need for ambulance transportation (1.5 hours), need for prescriptions to be filled at the hospital (1.4 hours), and for patients whose final test was a procedure (1.2 hours) or consult (1.1 hours).
Median discharge time was 7.6 hours. Longer discharge duration was associated with discharge to a location other than home (28.9 hours), need for consultation (14.8 hours), or need for a procedure (13.4 hours) before discharge.
African-American race, gender, age, and comorbid psychiatric and substance abuse disorders were not associated with either late or prolonged discharges.
Bottom line: Final-day tests, procedures, and consults, as well as complex discharge arrangements, prolong and delay discharges more than the characteristics of patients themselves.
Citation: Chen LM, Freitag MH, Franco M, Sullivan CD, Dickson C, Brancati FL. Natural history of late discharges from a general medical ward. J Hosp Med. 2009;4(4):226-233.
Administration of Parenteral Medication a Common Point at Which Errors Occur in ICUs
Clinical question: To what extent are medication administration errors a problem across ICUs, and what are some ways to prevent them?
Background: High-acuity and complex systems increase the likelihood of medical errors in ICUs. The first multinational Sentinel Events Evaluation study reported an ICU medication error rate of 10.5 per 100 patient days at the prescription and administration stages of medication delivery.
Study design: Multinational observational, prospective, cross-sectional study.
Setting: One hundred thirteen ICUs in 27 countries on five continents.
Synopsis: This study addressed five types of medication error at the administration stage in the ICU in a 24-hour timeframe: wrong drug, wrong dose, wrong route, wrong time, and missed medication. The main outcome measures were the number and impact of administration errors, the distribution of error characteristics, and the distribution of contributing and preventive factors.
In the 1,328 critically ill patients included in the study, 861 medication errors were reported by structured questionnaire; 441 patients were affected by the errors. The prevalence was 74.5 errors per 100 patient days, and 12 patients (0.9%) suffered permanent harm or death. Most medication administration errors occurred during routine care, not during extraordinary situations. Most were omission errors.
This study is limited by its observational design and by the fact that self-reporting also carries the risk of under-reporting.
This study points out several ways to reduce medication errors. An independent predictor of decreased risk of medication errors of all types is an established incident reporting system. Routine checking of infusion pumps at every nursing shift change also reduced this risk.
Bottom line: This study confirmed that the administration of parenteral medications is a vulnerable point across many ICUs, and incident reporting systems and routine checks of infusion pumps are effective ways to reduce the risk of this type of error.
Citation: Valentin A, Capuzzo M, Guidet B, et al. Errors in administration of parenteral drugs in intensive care units: multinational prospective study. BMJ. 2009;338:b814. TH