Patient Care

In the Literature


In This Edition

Literature at a Glance

A guide to this month’s studies

Commonly Available Clinical Variables Predict 30-Day Readmissions for Community-Acquired Pneumonia

Clinical question: What are the risk factors for 30-day readmission in patients hospitalized for community-acquired pneumonia (CAP)?

Background: CAP is a common admission diagnosis associated with significant morbidity, mortality, and resource utilization. While prior data suggested that patients who survive a hospitalization for CAP are particularly vulnerable to readmission, few studies have examined the risk factors for readmission in this population.

Study design: Prospective, observational study.

Setting: A 400-bed teaching hospital in northern Spain.

Synopsis: From 2003 to 2005, this study consecutively enrolled 1,117 patients who were discharged after hospitalization for CAP. Eighty-one patients (7.2%) were readmitted within 30 days of discharge; 29 (35.8%) of these patients were rehospitalized for pneumonia-related causes.

Variables associated with pneumonia-related rehospitalization were treatment failure (HR 2.9; 95% CI, 1.2-6.8) and one or more instability factors at hospital discharge—for example, vital-sign abnormalities or inability to take food or medications by mouth (HR 2.8; 95% CI, 1.3-6.2). Variables associated with readmission unrelated to pneumonia were age greater than 65 years (HR 4.5; 95% CI, 1.4-14.7), Charlson comorbidity index greater than 2 (HR 1.9; 95% CI, 1.0-3.4), and decompensated comorbidities during index hospitalization.

Patients with at least two of the above risk factors were at a significantly higher risk for 30-day hospital readmission (HR 3.37; 95% CI, 2.08-5.46).

Bottom line: The risk factors for readmission after hospitalization for CAP differed between the groups with readmissions related to pneumonia versus other causes. Patients at high risk for readmission can be identified using easily available clinical variables.

Citation: Capelastegui A, España Yandiola PP, Quintana JM, et al. Predictors of short-term rehospitalization following discharge of patients hospitalized with community-acquired pneumonia. Chest. 2009;136(4): 1079-1085.

Clinical Shorts


In a randomized study of 2,203 patients undergoing coronary-artery bypass surgery (CABG), the off-pump group had worse composite long-term outcomes compared with the on-pump group, without any significant difference in neuropsychiatric outcomes.

Citation: Shroyer AL, Grover FL, Hattler B, et al. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med. 2009;361(19):1827-1837.


In a double-blind, placebo-controlled, crossover trial, self-administered high-flow oxygen after onset of a cluster headache led to a higher rate of symptom resolution (78% vs. 20%) at 15 minutes, compared with placebo.

Citation: Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.

Combinations of Lipid-Lowering Agents No More Effective than High-Dose Statin Monotherapy

Clinical question: Is high-dose statin monotherapy better than combinations of lipid-lowering agents for dyslipidemia in adults at high risk for coronary artery disease?

Background: While current guidelines support the benefits of aggressive lipid targets, there is little to guide physicians as to the optimal strategy for attaining target lipid levels.

Study design: Systematic review.

Setting: North America, Europe, and Asia.

Synopsis: Very-low-strength evidence showed that statin-ezetimibe (two trials; N=439) and statin-fibrate (one trial; N=166) combinations did not reduce mortality more than high-dose statin monotherapy. No trial data were found comparing the effect of these two strategies on secondary endpoints, including myocardial infarction, stroke, or revascularization.

Two trials (N=295) suggested lower-target lipid levels were more often achieved with statin-ezetimibe combination therapy than with high-dose statin monotherapy (OR 7.21; 95% CI, 4.30-12.08).

Limitations of this systematic review include the small number of studies directly comparing the two strategies, the short duration of most of the studies included, the focus on surrogate outcomes, and the heterogeneity of the study populations’ risk for coronary artery disease. Few studies were available comparing combination therapies other than statin-ezetimibe.

Bottom line: Limited evidence suggests that the combination of a statin with another lipid-lowering agent does not improve clinical outcomes when compared with high-dose statin monotherapy. Low-quality evidence suggests that lower-target lipid levels were more often reached with statin-ezetimibe combination therapy than with high-dose statin monotherapy.

Citation: Sharma M, Ansari MT, Abou-Setta AM, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009;151(9):622-630.

Catheter Retention in Catheter-Related Coagulase-Negative Staphylococcal Bacteremia Is a Significant Risk Factor for Recurrent Infection

Clinical question: Should central venous catheters (CVC) be removed in patients with coagulase-negative staphylococcal catheter-related bloodstream infections (CRBSI)?

Background: Current guidelines for the management of coagulase-negative staphylococcal CRBSI do not recommend routine removal of the CVC, but are based on studies that did not use a strict definition of coagulase-negative staphylococcal CRBSI. Additionally, the studies did not look explicitly at the risk of recurrent infection.

Study design: Retrospective chart review.

Setting: Single academic medical center.

Synopsis: The study retrospectively evaluated 188 patients with coagulase-negative staphylococcal CRBSI. Immediate resolution of the infection was not influenced by the management of the CVC (retention vs. removal or exchange). However, using the multiple logistic regression technique, patients with catheter retention were found to be 6.6 times (95% CI, 1.8-23.9 times) more likely to have recurrence compared with those patients whose catheter was removed or exchanged.

Bottom line: While CVC management does not appear to have an impact on the acute resolution of infection, catheter retention is a significant risk factor for recurrent bacteremia.

Citation: Raad I, Kassar R, Ghannam D, Chaftari AM, Hachem R, Jiang Y. Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain? Clin Infect Dis. 2009;49(8):1187-1194.

Clinical Shorts


In this study, 22.8%, 11.1%, and 0.6% of long-term care facility residents were colonized with MDR gram-negative bacteria, MRSA, and VRE, respectively. Predictors of gram-negative colonization were length of stay, fecal incontinence, and antibiotic use.

Citation: O’Fallon E, Schreiber R, Kandel R, D’Agata EM. Multidrug-resistant gram-negative bacteria at a long-term care facility: assessment of residents, healthcare workers, and inanimate surfaces. Infect Control Hosp Epidemiol. 2009;30(12):1172-1179.


A case-control analysis using a United Kingdom-based general practice registry found that long-term use of statins was associated with a 22% reduction in the risk for gallstones requiring cholecystectomy.

Citation: Bodmer M, Brauchli YB, Krähenbühl S, Jick SS, Meier CR. Statin use and risk of gallstone disease followed by cholecystectomy. JAMA. 2009;302(18):2001-2007.

Revascularization Offers No Benefit over Medical Therapy for Renal-Artery Stenosis

Clinical question: Does revascularization plus medical therapy compared with medical therapy alone improve outcomes in patients with renal-artery stenosis?

Background: Renal-artery stenosis is associated with significant hypertension and renal dysfunction. Revascularization for atherosclerotic renal-artery stenosis can improve artery patency, but it remains unclear if it provides clinical benefit in terms of preserving renal function or reducing overall mortality.

Study design: Randomized, controlled trial.

Setting: Fifty-seven outpatient sites in the United Kingdom, Australia, and New Zealand.

Synopsis: The study randomized 806 patients with renal-artery stenosis to receive either medical therapy alone (N=403) or medical management plus endovascular revascularization (N=403).

The majority of the patients who underwent revascularization (95%) received a stent.

The data show no significant difference between the two groups in the rate of progression of renal dysfunction, systolic blood pressure, rates of adverse renal and cardiovascular events, and overall survival. Of the 359 patients who underwent revascularization, 23 (6%) experienced serious complications from the procedure, including two deaths and three cases of amputated toes or limbs.

The primary limitation of this trial is the population studied. The trial only included subjects for whom revascularization offered uncertain clinical benefits, according to their doctor. Those subjects for whom revascularization offered certain clinical benefits, as noted by their primary-care physician (PCP), were excluded from the study. Examples include patients presenting with rapidly progressive renal dysfunction or pulmonary edema thought to be a result of renal-artery stenosis.

Bottom line: Revascularization provides no benefit to most patients with renal-artery stenosis, and is associated with some risk.

Citation: ASTRAL investigators, Wheatley K, Ives N, et al. Revascularization versus medical therapy for renal-artery stenosis. N Eng J Med. 2009;361(20):1953-1962.

Dabigatran as Effective as Warfarin in Treatment of Acute VTE

Clinical question: Is dabigatran a safe and effective alternative to warfarin for treatment of acute VTE?

Background: Parenteral anticoagulation followed by warfarin is the standard of care for acute VTE. Warfarin requires frequent monitoring and has numerous drug and food interactions. Dabigatran, which the FDA has yet to approve for use in the U.S., is an oral direct thrombin inhibitor that does not require laboratory monitoring. The role of dabigatran in acute VTE has not been evaluated.

Study design: Randomized, double-blind, noninferiority trial.

Setting: Two hundred twenty-two clinical centers in 29 countries.

Synopsis: This study randomized 2,564 patients with documented VTE (either DVT or pulmonary embolism [PE]) to receive dabigatran 150mg twice daily or warfarin after at least five days of a parenteral anticoagulant. Warfarin was dose-adjusted to an INR goal of 2.0-3.0. The primary outcome was incidence of recurrent VTE and related deaths at six months.

A total of 2.4% of patients assigned to dabigatran and 2.1% of patients assigned to warfarin had recurrent VTE (HR 1.10; 95% CI, 0.8-1.5), which met criteria for noninferiority. Major bleeding occurred in 1.6% of patients assigned to dabigatran and 1.9% assigned to warfarin (HR 0.82; 95% CI, 0.45-1.48). There was no difference between groups in overall adverse effects. Discontinuation due to adverse events was 9% with dabigatran compared with 6.8% with warfarin (P=0.05). Dyspepsia was more common with dabigatran (P<0.001).

Bottom line: Following parenteral anticoagulation, dabigatran is a safe and effective alternative to warfarin for the treatment of acute VTE and does not require therapeutic monitoring.

Citation: Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352.

Clinical Shorts


In a randomized, double-blind, placebo-controlled trial in Thailand, an HIV vaccine reduced the risk of HIV by 31%. Vaccination did not affect CD4 count or viremia in those diagnosed with HIV.

Citation: Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361(23):2209-2220.


In a single-institution, retrospective, cohort analysis of prosthetic joint infections, 15% of cases involved gram-negative organisms. Of these, debridement alone resulted in more treatment failures than two-stage exchange or resection arthroplasties.

Citation: Hsieh PH, Lee MS, Hsu KY, Chang YH, Shih HN, Ueng SW. Gram-negative prosthetic joint infections: risk factors and outcome of treatment. Clin Infect Dis. 2009;49(7):1036-1043.


This large, population-based, case-control study in Denmark found that current glucocorticoid use increased the risk of first hospital diagnosis of atrial fibrillation or flutter, while former use did not.

Citation: Christiansen CF, Christensen S, Mehnert F, Cummings SR, Chapurlat RD, Sørensen HT. Glucocorticoid use and risk of atrial fibrillation or flutter: a population-based, case-control study. Arch Intern Med. 2009;169(18):1677-1683.


In an online survey, most physicians reported they were aware of and practiced according to published guidelines for healthcare-associated pneumonia (HCAP). However, testing showed that the majority did not choose guideline-concordant therapy.

Citation: Seymann GB, Di Francesco L, Sharpe B, et al. The HCAP gap: differences between self-reported practice patterns and published guidelines for health care-associated pneumonia. Clin Infect Dis. 2009;49(12):1868-1874.

Surgical Masks as Effective as N95 Respirators for Preventing Influenza

Clinical question: How effective are surgical masks compared with N95 respirators in protecting healthcare workers against influenza?

Background: Evidence surrounding the effectiveness of the surgical mask compared with the N95 respirator for protecting healthcare workers against influenza is sparse.

Study design: Randomized, controlled trial.

Setting: Eight hospitals in Ontario.

Synopsis: The study looked at 446 nurses working in EDs, medical units, and pediatric units randomized to use either a fit-tested N95 respirator or a surgical mask when caring for patients with febrile respiratory illness during the 2008-2009 flu season. The primary outcome measured was laboratory-confirmed influenza. Only a minority of the study participants (30% in the surgical mask group; 28% in the respirator group) received the influenza vaccine during the study year.

Influenza infection occurred with similar incidence in both the surgical-mask and N95 respirator groups (23.6% vs. 22.9%). A two-week audit period demonstrated solid adherence to the assigned respiratory protection device in both groups (11 out of 11 nurses were compliant in the surgical-mask group; six out of seven nurses were compliant in the respirator group).

The major limitation of this study is that it cannot be extrapolated to other settings where there is a high risk for aerosolization, such as intubation or bronchoscopy, where N95 respirators may be more effective than surgical masks.

Bottom line: Surgical masks are as effective as fit-tested N95 respirators in protecting healthcare workers against influenza in most settings.

Citation: Loeb M, Dafoe N, Mahony J, et al. Surgical mask vs. N95 respirator for preventing influenza among health care workers: a randomized trial. JAMA. 2009;302 (17):1865-1871.

Neither Major Illness Nor Noncardiac Surgery Associated with Long-Term Cognitive Decline in Older Patients

Clinical question: Is there a measurable and lasting cognitive decline in older adults following noncardiac surgery or major illness?

Background: Despite limited evidence, there is some concern that elderly patients are susceptible to significant, long-term deterioration in mental function following surgery or a major illness. Prior studies often have been limited by lack of information about the trajectory of surgical patients’ cognitive status before surgery and lack of relevant control groups.

Study design: Retrospective, cohort study.

Setting: Single outpatient research center.

Synopsis: The Alzheimer’s Disease Research Center (ADRC) at the University of Washington in St. Louis continually enrolls research subjects without regard to their baseline cognitive function and provides annual assessment of cognitive functioning.

From the ADRC database, 575 eligible research participants were identified. Of these, 361 had very mild or mild dementia at enrollment, and 214 had no dementia. Participants were then categorized into three groups: those who had undergone noncardiac surgery (N=180); those who had been admitted to the hospital with a major illness (N=119); and those who had experienced neither surgery nor major illness (N=276).

Cognitive trajectory did not differ between the three groups, although participants with baseline dementia declined more rapidly than participants without dementia. Although 23% of patients without dementia developed detectable evidence of dementia during the study period, this outcome was not more common following surgery or major illness.

As participants were assessed annually, this study does not address the issue of post-operative delirium or early cognitive impairment following surgery.

Bottom line: There is no evidence for a long-term effect on cognitive function independently attributable to noncardiac surgery or major illness.

Citation: Avidan MS, Searleman AC, Storandt M, et al. Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology. 2009;111(5):964-970.

Rapid-Response System Maturation Decreases Delays in Emergency Team Activation

Clinical question: Does the maturation of a rapid-response system (RRS) improve performance by decreasing delays in medical emergency team (MET) activation?

Background: RRSs have been widely embraced as a possible means to reduce inpatient cardiopulmonary arrests and unplanned ICU admissions. Assessment of RRSs early in their implementation might underestimate their long-term efficacy. Whether the use and performance of RRSs improve as they mature is currently unknown.

Study design: Observational, cohort study.

Setting: Single tertiary-care hospital.

Synopsis: A recent cohort of 200 patients receiving MET review was prospectively compared with a control cohort of 400 patients receiving an MET review five years earlier, at the start of RRS implementation. Information obtained on the two cohorts included demographics, timing of MET activation in relation to the first documented MET review criterion (activation delay), and patient outcomes.

Fewer patients in the recent cohort had delayed MET activation (22.0% vs. 40.3%). The recent cohort also was independently associated with a decreased risk of delayed activation (OR 0.45; 95% C.I., 0.30-0.67) and ICU admission (OR 0.5; 95% C.I., 0.32-0.78). Delayed MET activation independently was associated with greater risk of unplanned ICU admission (OR 1.79; 95% C.I., 1.33-2.93) and hospital mortality (OR 2.18; 95% C.I., 1.42-3.33).

The study is limited by its observational nature, and thus the association between greater delay and unfavorable outcomes should not infer causality.

Bottom line: The maturation of a RRS decreases delays in MET activation. RRSs might need to mature before their full impact is felt.

Citation: Calzavacca P, Licari E, Tee A, et al. The impact of Rapid Response System on delayed emergency team activation patient characteristics and outcomes—a follow-up study. Resuscitation. 2010;81(1):31-35. TH

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