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.
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