Sarah Anand, MD

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Perioperative SSRI use associated with adverse surgical outcomes
2. Copper-surfaced rooms reduce health-care-acquired infections
3. Glucocorticoid therapy for five days not inferior to 14 days for COPD exacerbation
4. Patient preference for participation in medical decision-making may be associated with increased resource utilization
5. Early parenteral nutrition in critically ill adults does not significantly affect mortality or infection rates
6. Aggressive fluid and sodium restriction in acute decompensated heart failure did not improve outcomes
7. Lower rate of pacemaker, defibrillator device-pocket hematoma without anticoagulation interruption
8. Prophylactic penicillin decreased risk of recurrent leg cellulitis
9. Universal ICU decolonization reduced rates of mrsa clinical isolates and bloodstream infection
10. Intensive blood-pressure lowering in intracerebral hemorrhage did not reduce death or severe disability

Perioperative SSRI Use Associated with Adverse Surgical Outcomes

Clinical question: Does selective serotonin reuptake inhibitor (SSRI) use during hospitalization for surgery increase the risk of adverse perioperative outcomes?

Background: SSRIs commonly are prescribed but are associated with a small but higher risk for hemorrhage, arrhythmia, and sudden death. Single-site studies have described an association between SSRIs and adverse perioperative outcomes, but larger studies utilizing a broad range of surgical cases are lacking.

Study design: Retrospective cohort study.

Setting: Three hundred hospitals concentrated in the Southern U.S.

Synopsis: Using the “Perspective” database, this study examined 530,416 patients age >18 years undergoing major elective surgery, 72,540 (13.7%) of whom received an SSRI. Regression analysis showed patients receiving an SSRI had higher odds of mortality (OR 1.2, 95% CI [1.07-1.36]), higher odds of 30-day readmission (OR 1.22 [1.18-1.26]), and higher odds for bleeding (1.09 [1.04-1.15]). When the analysis was restricted to only patients with a diagnosis of depression, a higher risk of bleeding and readmission persisted.

This study reaffirms an association but does not establish a causal relationship between SSRI use and adverse perioperative outcomes. SSRI use may be a surrogate for other factors, including more severe mood disorders, poorer functional status, or chronic pain. Additionally, no information has been provided as to optimal duration of withholding SSRIs preoperatively. As such, it may be premature for hospitalists involved in perioperative care to modify recommendations based on this study.

Bottom line: Perioperative SSRI use is associated with an increased risk of bleeding and 30-day readmission.

Citation: Auerbach AD, Vittinghoff E, Maselli J, et al. Perioperative use of selective serotonin reuptake inhibitors and risks for adverse outcomes of surgery. JAMA Intern Med. 2013;173(12):1075-1081.

Copper-Surfaced Rooms Reduce Health-Care-Acquired Infections

Clinical question: Can copper alloy surfaces in ICU rooms lower rates of health-care-acquired infections (HAIs)?

Background: Environmental contamination is a potential source of HAIs. Copper has intrinsic broad-spectrum antimicrobial properties. This study tests the efficacy copper-surfaced items in hospital rooms have in preventing HAIs.

Study design: Randomized controlled trial.

Setting: Medical ICUs at Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center in Charleston, and the Memorial Sloan Kettering Cancer Center in New York City.

Synopsis: Six hundred fifty ICU patients were randomized to receive care either in rooms with copper surfacing on commonly handled patient care objects or in traditional rooms. Patients were screened for methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) on admission. The proportion of patients that developed either an HAI and/or MRSA or VRE colonization was significantly lower among patients in rooms with the copper-surfaced items (0.071 vs. 0.128; P=0.02). The rate of HAIs alone was also lower in the rooms with the copper (0.034 vs. 0.081; P=0.013).

A potential limitation to this study is that the rooms with copper items appeared different than traditional rooms, and therefore might have changed the behavior of health-care workers. Further, it is unclear how much copper surfacing would be necessary on general wards, where patients are more mobile. Still, HAIs are associated with longer lengths of stay and higher 30-day readmission rates, so these encouraging results warrant additional investigation into antimicrobial copper-alloy surfaces.

Bottom line: Copper-surfaced objects reduce HAI rates in ICU patients.

Citation: Salgado CD, Sepkowitz, KA, John JF, et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol. 2013;34(5):479-486.

Glucocorticoid Therapy for Five Days Not Inferior to 14 Days for COPD Exacerbation

Clinical question: Do short-course glucocorticoids work as well as conventional long courses for COPD exacerbation?

Background: International guidelines advocate a seven- to 14-day treatment course with glucocorticoids for COPD exacerbation, but the optimal duration of treatment is not known, and there are potential risks associated with glucocorticoid exposure.

Study design: Randomized, noninferiority, multicenter trial.

Setting: Five Swiss teaching hospitals.

Synopsis: Three hundred fourteen patients presenting to the ED with acute COPD exacerbation and without a history of asthma were randomized to receive treatment with 40 mg prednisone daily for either five or 14 days in a placebo-controlled, double-blinded fashion. There was no significant difference in the primary endpoint of re-exacerbation within six months. Patients in the five-day glucocorticoid group compared with the 14-day group were exposed to significantly less glucocorticoid.

Bottom line: Treatment for five days with glucocorticoids was not inferior to 14 days for acute COPD exacerbations with regard to re-exacerbations within six months and resulted in less glucocorticoid exposure overall.

Citation: Leuppi JF, Schuetz P, Bingisser R, et al. Short-term vs. conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE Randomized Clinical Trial. JAMA. 2013;390(21):2223-2231.

Patient Preference for Participation in Medical Decision-Making May Be Associated with Increased Resource Utilization

Clinical question: Do patient preferences for participation in medical decision-making affect health-care utilization?

Background: Patient participation in medical decision-making has been associated with improved patient satisfaction and health outcomes. There is little evidence to support theories that patient preferences might decrease or increase health-care utilization.

Study design: Survey study in academic research setting.

Setting: University of Chicago Medical Center.

Synopsis: More than 21,700 patients admitted to a general internal-medicine service completed a survey that included questions regarding preferences about receiving medical information and participation in medical decision-making. Survey data were linked with administrative data, including length of stay and total hospitalization costs.

Most patients (96.3%) expressed interest in receiving information about their illness and treatment options, but the majority of patients (71.1%) also expressed a preference to leave medical decision-making to their physician. Patients who preferred to participate in medical decision-making had significantly longer hospital LOS and higher total hospitalization cost.

Bottom line: Participation in medical decision-making significantly increased LOS and total costs.

Citation: Tak HJ, Ruhnke GW, Meltzer DO. Association of patient preferences for participation in decision making with length of stay and costs among hospitalized patients. JAMA Intern Med. 2013;173(13):1195-1205. doi: 10.1001/jamainternmed.2013.6048.

Early Parenteral Nutrition in Critically Ill Adults Does Not Significantly Affect Mortality or Infection Rates

Clinical question: Does providing early parenteral nutrition to critically ill adults with short-term relative contraindications to early enteral nutrition affect outcomes?

Background: The appropriate use of parenteral nutrition in critically ill adults is controversial. A systematic review found that critically ill patients randomized to receive early parenteral nutrition had significantly lower mortality but increased infection rates compared with standard care. A large-scale randomized trial was necessary to confirm the results.

Study design: Multicenter, randomized, single-blinded, controlled trial.

Setting: ICUs in 31 tertiary-care and community hospitals in Australia and New Zealand.

Synopsis: Researchers randomized 1,372 critically ill adults with relative contraindications to early enteral nutrition upon admission to the ICU to receive early parenteral nutrition or standard care. Early parenteral nutrition was started an average of 44 minutes after randomization. Clinicians defined standard care, with most patients remaining unfed for 2.8 days after randomization. Results were analyzed by intention-to-treat analysis, and loss to follow-up was 1%.

There was no significant difference in the primary outcome of 60-day mortality. Early parenteral nutrition patients received significantly fewer days of invasive ventilation, but did not have shorter ICU or hospital stays. Early parenteral nutrition patients experienced significantly less muscle-wasting and fat loss. There was no significant difference in new infection rates.

Bottom line: Early parenteral nutrition in critically ill adults resulted in significantly fewer days of invasive mechanical ventilation but did not cause a significant difference in length of stay, infection rates, or 60-day mortality.

Citation: Doig GS, Simpson F, Sweetman EA, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition. JAMA. 2013;309(20): 2130-2138.

Aggressive Fluid and Sodium Restriction in Acute Decompensated Heart Failure Did Not Improve Outcomes

Clinical question: Does aggressive fluid and sodium restriction in acute decompensated heart failure (ADHF) result in increased weight loss, improved clinical stability, or decreased 30-day readmission rate?

Background: Fluid and sodium restriction are standard nonpharmacologic measures used in the management of ADHF in hospitalized patients, despite an absence of data to support their efficacy.

Study design: Randomized, controlled clinical trial with blinded outcome assessments.

Setting: A public teaching hospital in Brazil.

Synopsis: Seventy-five patients hospitalized with ADHF were randomized to receive aggressive fluid (800 mL/day) and sodium restriction (800 mg/day) or liberal intake (at least 2.5 L/day fluid, 3 to 5 g/day sodium). There were no significant between-group differences in diuretic administration. The primary outcomes of weight loss and clinical stability at three days were not significantly different between the groups. The heart-failure-specific readmission rate at 30 days was not significantly different between the groups. The aggressive restriction group had significantly worse thirst.

The study is limited by the small fraction of patients enrolled (9.2% of 813 screened) and homogenous population. Additional confirmatory trials likely are needed to change the standard of care, but this study demonstrated that aggressive fluid and sodium restriction does not benefit hospitalized patients with ADHF.

Bottom line: Aggressive fluid and sodium restriction in hospitalized patients with ADHF does not result in improved short-term weight loss, clinical stability, or decreased 30-day readmission rate, but it does cause significantly worse thirst.

Citation: Aliti GB, Rabelo ER, Clausell N, et al. Aggressive fluid and sodium restriction in acute decompensated heart failure. JAMA Intern Med. 2013;173(12):1058-1064.

Lower Rate of Pacemaker, Defibrillator Device-Pocket Hematoma without Anticoagulation Interruption

Clinical question: Is it safer to place a pacemaker or implantable cardioverter-defibrillator (ICD) while on therapeutic warfarin versus bridging with heparin/low-molecular-weight heparin (LMWH)?

Background: Current guidelines recommend bridging with heparin or LMWH for patients at high risk for thromboembolic events around the time of pacemaker or ICD placement, but it is associated with significant risk of device-pocket hematoma. Some centers place pacemakers and ICDs without interruption of warfarin. However, there are limited data to support the safety of this approach.

Study design: Multicenter, single-blinded, randomized, controlled trial.

Setting: Seventeen centers in Canada and one center in Brazil.

Synopsis: Patients with a predicted annual risk of 5% of thromboembolism were randomized to continue anticoagulation with warfarin (median INR 2.3) or to bridge therapy with heparin or LMWH; they then evaluated the incidence of clinically significant hematoma requiring prolonged hospitalization, interruption of anticoagulation therapy, or further surgical intervention. After reviewing the data on 668 patients, the Data and Safety Monitoring Board recommended termination of the study given a significantly lower rate of device-pocket hematoma in the warfarin group (3.5%) compared with the bridge group (16%) with RR 0.19 (95% CI 0.10-0.36, P<0.001). Otherwise, major surgical and thromboembolic complications were rare and not significantly different in both groups.

Bottom line: Continued warfarin therapy was associated with significantly reduced incidence of device-pocket hematoma compared with bridge with heparin or LMWH.

Citation: Birnie DH, Healey JS, Wells GA, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013;368(22):2084-2093.

Prophylactic Penicillin Decreased Risk of Recurrent Leg Cellulitis

Clinical question: Does prophylactic, low-dose penicillin prevent recurrent cellulitis in patients with a history of two or more episodes of cellulitis?

Background: Some guidelines recommend prophylactic antibiotics for recurrent leg cellulitis, but there is no large randomized trial to support this practice, and clinical opinion is mixed.

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

Setting: Twenty-eight hospitals in the United Kingdom and Ireland.

Synopsis: Researchers randomized 274 patients with recurrent episodes of leg cellulitis (at least two episodes within the previous three years) to low-dose penicillin (250 mg) or placebo for 12 months and followed them for more than three years. During the prophylactic period, the penicillin group had a 45% reduction in the risk of a repeat cellulitis as compared to placebo (22% vs. 37%), equivalent to a number needed to treat to prevent a first recurrent cellulitis of five. The number of repeat episodes of cellulitis was lower overall in penicillin compared with the placebo group (119 vs. 164, P=0.02), although no significant difference was noted during the three-year follow-up period.

Factors associated with prophylaxis failure included three or more previous episodes of cellulitis, body mass index of 33 kg/m² or higher, and the presence of edema. No significant difference in adverse events was noted between the groups. Complete follow-up data was not available for participants during the follow-up period. Further study is needed to assess the long-term adverse effects and the duration of prophylaxis needed.

Bottom line: Prophylactic penicillin was effective in preventing recurrent leg cellulitis without increasing adverse effects, but its protective effect gradually declined once discontinued.

Citation: Thomas KS, Crook AM, Nunn AJ, et al. Penicillin to prevent recurrent leg cellulitis. N Engl J Med. 2013;368(18):1695-1703.

Universal ICU Decolonization Reduced Rates of MRSA Clinical Isolates and Bloodstream Infection

Clinical question: What is the most effective decolonization strategy for reducing methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens in ICUs?

Background: Studies have shown that daily chlorhexidine bathing of all patients in ICUs reduced MRSA acquisition and bloodstream infection from all pathogens. However, this universal strategy has not been compared to MRSA screening and contact precautions alone, or to targeted decolonization of MRSA carriers.

Study design: Cluster-randomized comparative-effectiveness trial.

Setting: Adult ICUs in 43 Hospital Corporation of America (HCA) hospitals in 16 states.

Synopsis: All adult ICUs in a given hospital were randomized to one of three infection prevention strategies: Group 1 continued MRSA screening and isolation; Group 2 performed screening, isolation, and decolonization of MRSA carriers; and Group 3 implemented universal decolonization with intranasal mupirocin and daily bathing with chlorhexidine-impregnated cloths but no screening.

Forty-three hospitals, including 74 ICUs and 74,256 patients, underwent randomization. Significant reductions in the primary outcome of ICU-attributable MRSA clinical isolates (excluding MRSA screening tests) and the secondary outcome of bloodstream infection due to any pathogen were demonstrated across the three groups. One bloodstream infection was prevented for every 54 patients who underwent decolonization. Formal cost-effectiveness analysis was not performed.

Bottom line: In the ICU, universal decolonization was more effective than screening and isolation or targeted decolonization in the reduction of clinical MRSA isolates and bloodstream infection due to any pathogen, although monitoring for emerging resistance is necessary.

Citation: Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-2265.

Intensive Blood-Pressure Lowering in Intracerebral Hemorrhage Did Not Reduce Death or Severe Disability

Clinical question: What is the efficacy and safety of early intensive blood-pressure lowering in patients with acute intracerebral hemorrhage?

Background: After intracerebral hemorrhage, blood pressure often becomes elevated and is a predictor of outcome. It is not known whether rapid lowering of blood pressure would improve outcome.

Study design: International, multicenter, prospective, randomized, open-treatment, blinded end-point trial.

Setting: One hundred forty-four hospitals in 21 countries.

Synopsis: Researchers randomly assigned 2,839 patients with intracerebral hemorrhage in the previous six hours to intensive blood-pressure lowering with target systolic blood pressure of <140 mmHg within one hour, or guideline-recommended treatment with target systolic blood pressure of <180 mmHg. The mean systolic blood pressure achieved was 150 mmHg in the intensive-treatment group and 164 mmHg in the standard-treatment group.

There was no significant difference between the two groups in the primary outcome of death or major disability. A pre-specified ordinal analysis of modified Rankin score (score of 0 indicates no symptoms; a score of 5 indicates severe disability) did show significantly lower modified Rankin scores with intensive treatment. There was no difference between the two groups in the rate of serious adverse events.

Bottom line: Early intensive blood-pressure lowering in patients with acute intracerebral hemorrhage did not reduce death or major disability, although there may be improved functional outcomes with intensive blood-pressure lowering.

Citation: Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355-2365.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Perioperative SSRI use associated with adverse surgical outcomes
2. Copper-surfaced rooms reduce health-care-acquired infections
3. Glucocorticoid therapy for five days not inferior to 14 days for COPD exacerbation
4. Patient preference for participation in medical decision-making may be associated with increased resource utilization
5. Early parenteral nutrition in critically ill adults does not significantly affect mortality or infection rates
6. Aggressive fluid and sodium restriction in acute decompensated heart failure did not improve outcomes
7. Lower rate of pacemaker, defibrillator device-pocket hematoma without anticoagulation interruption
8. Prophylactic penicillin decreased risk of recurrent leg cellulitis
9. Universal ICU decolonization reduced rates of mrsa clinical isolates and bloodstream infection
10. Intensive blood-pressure lowering in intracerebral hemorrhage did not reduce death or severe disability

Perioperative SSRI Use Associated with Adverse Surgical Outcomes

Clinical question: Does selective serotonin reuptake inhibitor (SSRI) use during hospitalization for surgery increase the risk of adverse perioperative outcomes?

Background: SSRIs commonly are prescribed but are associated with a small but higher risk for hemorrhage, arrhythmia, and sudden death. Single-site studies have described an association between SSRIs and adverse perioperative outcomes, but larger studies utilizing a broad range of surgical cases are lacking.

Study design: Retrospective cohort study.

Setting: Three hundred hospitals concentrated in the Southern U.S.

Synopsis: Using the “Perspective” database, this study examined 530,416 patients age >18 years undergoing major elective surgery, 72,540 (13.7%) of whom received an SSRI. Regression analysis showed patients receiving an SSRI had higher odds of mortality (OR 1.2, 95% CI [1.07-1.36]), higher odds of 30-day readmission (OR 1.22 [1.18-1.26]), and higher odds for bleeding (1.09 [1.04-1.15]). When the analysis was restricted to only patients with a diagnosis of depression, a higher risk of bleeding and readmission persisted.

This study reaffirms an association but does not establish a causal relationship between SSRI use and adverse perioperative outcomes. SSRI use may be a surrogate for other factors, including more severe mood disorders, poorer functional status, or chronic pain. Additionally, no information has been provided as to optimal duration of withholding SSRIs preoperatively. As such, it may be premature for hospitalists involved in perioperative care to modify recommendations based on this study.

Bottom line: Perioperative SSRI use is associated with an increased risk of bleeding and 30-day readmission.

Citation: Auerbach AD, Vittinghoff E, Maselli J, et al. Perioperative use of selective serotonin reuptake inhibitors and risks for adverse outcomes of surgery. JAMA Intern Med. 2013;173(12):1075-1081.

Copper-Surfaced Rooms Reduce Health-Care-Acquired Infections

Clinical question: Can copper alloy surfaces in ICU rooms lower rates of health-care-acquired infections (HAIs)?

Background: Environmental contamination is a potential source of HAIs. Copper has intrinsic broad-spectrum antimicrobial properties. This study tests the efficacy copper-surfaced items in hospital rooms have in preventing HAIs.

Study design: Randomized controlled trial.

Setting: Medical ICUs at Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center in Charleston, and the Memorial Sloan Kettering Cancer Center in New York City.

Synopsis: Six hundred fifty ICU patients were randomized to receive care either in rooms with copper surfacing on commonly handled patient care objects or in traditional rooms. Patients were screened for methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) on admission. The proportion of patients that developed either an HAI and/or MRSA or VRE colonization was significantly lower among patients in rooms with the copper-surfaced items (0.071 vs. 0.128; P=0.02). The rate of HAIs alone was also lower in the rooms with the copper (0.034 vs. 0.081; P=0.013).

A potential limitation to this study is that the rooms with copper items appeared different than traditional rooms, and therefore might have changed the behavior of health-care workers. Further, it is unclear how much copper surfacing would be necessary on general wards, where patients are more mobile. Still, HAIs are associated with longer lengths of stay and higher 30-day readmission rates, so these encouraging results warrant additional investigation into antimicrobial copper-alloy surfaces.

Bottom line: Copper-surfaced objects reduce HAI rates in ICU patients.

Citation: Salgado CD, Sepkowitz, KA, John JF, et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol. 2013;34(5):479-486.

Glucocorticoid Therapy for Five Days Not Inferior to 14 Days for COPD Exacerbation

Clinical question: Do short-course glucocorticoids work as well as conventional long courses for COPD exacerbation?

Background: International guidelines advocate a seven- to 14-day treatment course with glucocorticoids for COPD exacerbation, but the optimal duration of treatment is not known, and there are potential risks associated with glucocorticoid exposure.

Study design: Randomized, noninferiority, multicenter trial.

Setting: Five Swiss teaching hospitals.

Synopsis: Three hundred fourteen patients presenting to the ED with acute COPD exacerbation and without a history of asthma were randomized to receive treatment with 40 mg prednisone daily for either five or 14 days in a placebo-controlled, double-blinded fashion. There was no significant difference in the primary endpoint of re-exacerbation within six months. Patients in the five-day glucocorticoid group compared with the 14-day group were exposed to significantly less glucocorticoid.

Bottom line: Treatment for five days with glucocorticoids was not inferior to 14 days for acute COPD exacerbations with regard to re-exacerbations within six months and resulted in less glucocorticoid exposure overall.

Citation: Leuppi JF, Schuetz P, Bingisser R, et al. Short-term vs. conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE Randomized Clinical Trial. JAMA. 2013;390(21):2223-2231.

Patient Preference for Participation in Medical Decision-Making May Be Associated with Increased Resource Utilization

Clinical question: Do patient preferences for participation in medical decision-making affect health-care utilization?

Background: Patient participation in medical decision-making has been associated with improved patient satisfaction and health outcomes. There is little evidence to support theories that patient preferences might decrease or increase health-care utilization.

Study design: Survey study in academic research setting.

Setting: University of Chicago Medical Center.

Synopsis: More than 21,700 patients admitted to a general internal-medicine service completed a survey that included questions regarding preferences about receiving medical information and participation in medical decision-making. Survey data were linked with administrative data, including length of stay and total hospitalization costs.

Most patients (96.3%) expressed interest in receiving information about their illness and treatment options, but the majority of patients (71.1%) also expressed a preference to leave medical decision-making to their physician. Patients who preferred to participate in medical decision-making had significantly longer hospital LOS and higher total hospitalization cost.

Bottom line: Participation in medical decision-making significantly increased LOS and total costs.

Citation: Tak HJ, Ruhnke GW, Meltzer DO. Association of patient preferences for participation in decision making with length of stay and costs among hospitalized patients. JAMA Intern Med. 2013;173(13):1195-1205. doi: 10.1001/jamainternmed.2013.6048.

Early Parenteral Nutrition in Critically Ill Adults Does Not Significantly Affect Mortality or Infection Rates

Clinical question: Does providing early parenteral nutrition to critically ill adults with short-term relative contraindications to early enteral nutrition affect outcomes?

Background: The appropriate use of parenteral nutrition in critically ill adults is controversial. A systematic review found that critically ill patients randomized to receive early parenteral nutrition had significantly lower mortality but increased infection rates compared with standard care. A large-scale randomized trial was necessary to confirm the results.

Study design: Multicenter, randomized, single-blinded, controlled trial.

Setting: ICUs in 31 tertiary-care and community hospitals in Australia and New Zealand.

Synopsis: Researchers randomized 1,372 critically ill adults with relative contraindications to early enteral nutrition upon admission to the ICU to receive early parenteral nutrition or standard care. Early parenteral nutrition was started an average of 44 minutes after randomization. Clinicians defined standard care, with most patients remaining unfed for 2.8 days after randomization. Results were analyzed by intention-to-treat analysis, and loss to follow-up was 1%.

There was no significant difference in the primary outcome of 60-day mortality. Early parenteral nutrition patients received significantly fewer days of invasive ventilation, but did not have shorter ICU or hospital stays. Early parenteral nutrition patients experienced significantly less muscle-wasting and fat loss. There was no significant difference in new infection rates.

Bottom line: Early parenteral nutrition in critically ill adults resulted in significantly fewer days of invasive mechanical ventilation but did not cause a significant difference in length of stay, infection rates, or 60-day mortality.

Citation: Doig GS, Simpson F, Sweetman EA, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition. JAMA. 2013;309(20): 2130-2138.

Aggressive Fluid and Sodium Restriction in Acute Decompensated Heart Failure Did Not Improve Outcomes

Clinical question: Does aggressive fluid and sodium restriction in acute decompensated heart failure (ADHF) result in increased weight loss, improved clinical stability, or decreased 30-day readmission rate?

Background: Fluid and sodium restriction are standard nonpharmacologic measures used in the management of ADHF in hospitalized patients, despite an absence of data to support their efficacy.

Study design: Randomized, controlled clinical trial with blinded outcome assessments.

Setting: A public teaching hospital in Brazil.

Synopsis: Seventy-five patients hospitalized with ADHF were randomized to receive aggressive fluid (800 mL/day) and sodium restriction (800 mg/day) or liberal intake (at least 2.5 L/day fluid, 3 to 5 g/day sodium). There were no significant between-group differences in diuretic administration. The primary outcomes of weight loss and clinical stability at three days were not significantly different between the groups. The heart-failure-specific readmission rate at 30 days was not significantly different between the groups. The aggressive restriction group had significantly worse thirst.

The study is limited by the small fraction of patients enrolled (9.2% of 813 screened) and homogenous population. Additional confirmatory trials likely are needed to change the standard of care, but this study demonstrated that aggressive fluid and sodium restriction does not benefit hospitalized patients with ADHF.

Bottom line: Aggressive fluid and sodium restriction in hospitalized patients with ADHF does not result in improved short-term weight loss, clinical stability, or decreased 30-day readmission rate, but it does cause significantly worse thirst.

Citation: Aliti GB, Rabelo ER, Clausell N, et al. Aggressive fluid and sodium restriction in acute decompensated heart failure. JAMA Intern Med. 2013;173(12):1058-1064.

Lower Rate of Pacemaker, Defibrillator Device-Pocket Hematoma without Anticoagulation Interruption

Clinical question: Is it safer to place a pacemaker or implantable cardioverter-defibrillator (ICD) while on therapeutic warfarin versus bridging with heparin/low-molecular-weight heparin (LMWH)?

Background: Current guidelines recommend bridging with heparin or LMWH for patients at high risk for thromboembolic events around the time of pacemaker or ICD placement, but it is associated with significant risk of device-pocket hematoma. Some centers place pacemakers and ICDs without interruption of warfarin. However, there are limited data to support the safety of this approach.

Study design: Multicenter, single-blinded, randomized, controlled trial.

Setting: Seventeen centers in Canada and one center in Brazil.

Synopsis: Patients with a predicted annual risk of 5% of thromboembolism were randomized to continue anticoagulation with warfarin (median INR 2.3) or to bridge therapy with heparin or LMWH; they then evaluated the incidence of clinically significant hematoma requiring prolonged hospitalization, interruption of anticoagulation therapy, or further surgical intervention. After reviewing the data on 668 patients, the Data and Safety Monitoring Board recommended termination of the study given a significantly lower rate of device-pocket hematoma in the warfarin group (3.5%) compared with the bridge group (16%) with RR 0.19 (95% CI 0.10-0.36, P<0.001). Otherwise, major surgical and thromboembolic complications were rare and not significantly different in both groups.

Bottom line: Continued warfarin therapy was associated with significantly reduced incidence of device-pocket hematoma compared with bridge with heparin or LMWH.

Citation: Birnie DH, Healey JS, Wells GA, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013;368(22):2084-2093.

Prophylactic Penicillin Decreased Risk of Recurrent Leg Cellulitis

Clinical question: Does prophylactic, low-dose penicillin prevent recurrent cellulitis in patients with a history of two or more episodes of cellulitis?

Background: Some guidelines recommend prophylactic antibiotics for recurrent leg cellulitis, but there is no large randomized trial to support this practice, and clinical opinion is mixed.

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

Setting: Twenty-eight hospitals in the United Kingdom and Ireland.

Synopsis: Researchers randomized 274 patients with recurrent episodes of leg cellulitis (at least two episodes within the previous three years) to low-dose penicillin (250 mg) or placebo for 12 months and followed them for more than three years. During the prophylactic period, the penicillin group had a 45% reduction in the risk of a repeat cellulitis as compared to placebo (22% vs. 37%), equivalent to a number needed to treat to prevent a first recurrent cellulitis of five. The number of repeat episodes of cellulitis was lower overall in penicillin compared with the placebo group (119 vs. 164, P=0.02), although no significant difference was noted during the three-year follow-up period.

Factors associated with prophylaxis failure included three or more previous episodes of cellulitis, body mass index of 33 kg/m² or higher, and the presence of edema. No significant difference in adverse events was noted between the groups. Complete follow-up data was not available for participants during the follow-up period. Further study is needed to assess the long-term adverse effects and the duration of prophylaxis needed.

Bottom line: Prophylactic penicillin was effective in preventing recurrent leg cellulitis without increasing adverse effects, but its protective effect gradually declined once discontinued.

Citation: Thomas KS, Crook AM, Nunn AJ, et al. Penicillin to prevent recurrent leg cellulitis. N Engl J Med. 2013;368(18):1695-1703.

Universal ICU Decolonization Reduced Rates of MRSA Clinical Isolates and Bloodstream Infection

Clinical question: What is the most effective decolonization strategy for reducing methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens in ICUs?

Background: Studies have shown that daily chlorhexidine bathing of all patients in ICUs reduced MRSA acquisition and bloodstream infection from all pathogens. However, this universal strategy has not been compared to MRSA screening and contact precautions alone, or to targeted decolonization of MRSA carriers.

Study design: Cluster-randomized comparative-effectiveness trial.

Setting: Adult ICUs in 43 Hospital Corporation of America (HCA) hospitals in 16 states.

Synopsis: All adult ICUs in a given hospital were randomized to one of three infection prevention strategies: Group 1 continued MRSA screening and isolation; Group 2 performed screening, isolation, and decolonization of MRSA carriers; and Group 3 implemented universal decolonization with intranasal mupirocin and daily bathing with chlorhexidine-impregnated cloths but no screening.

Forty-three hospitals, including 74 ICUs and 74,256 patients, underwent randomization. Significant reductions in the primary outcome of ICU-attributable MRSA clinical isolates (excluding MRSA screening tests) and the secondary outcome of bloodstream infection due to any pathogen were demonstrated across the three groups. One bloodstream infection was prevented for every 54 patients who underwent decolonization. Formal cost-effectiveness analysis was not performed.

Bottom line: In the ICU, universal decolonization was more effective than screening and isolation or targeted decolonization in the reduction of clinical MRSA isolates and bloodstream infection due to any pathogen, although monitoring for emerging resistance is necessary.

Citation: Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-2265.

Intensive Blood-Pressure Lowering in Intracerebral Hemorrhage Did Not Reduce Death or Severe Disability

Clinical question: What is the efficacy and safety of early intensive blood-pressure lowering in patients with acute intracerebral hemorrhage?

Background: After intracerebral hemorrhage, blood pressure often becomes elevated and is a predictor of outcome. It is not known whether rapid lowering of blood pressure would improve outcome.

Study design: International, multicenter, prospective, randomized, open-treatment, blinded end-point trial.

Setting: One hundred forty-four hospitals in 21 countries.

Synopsis: Researchers randomly assigned 2,839 patients with intracerebral hemorrhage in the previous six hours to intensive blood-pressure lowering with target systolic blood pressure of <140 mmHg within one hour, or guideline-recommended treatment with target systolic blood pressure of <180 mmHg. The mean systolic blood pressure achieved was 150 mmHg in the intensive-treatment group and 164 mmHg in the standard-treatment group.

There was no significant difference between the two groups in the primary outcome of death or major disability. A pre-specified ordinal analysis of modified Rankin score (score of 0 indicates no symptoms; a score of 5 indicates severe disability) did show significantly lower modified Rankin scores with intensive treatment. There was no difference between the two groups in the rate of serious adverse events.

Bottom line: Early intensive blood-pressure lowering in patients with acute intracerebral hemorrhage did not reduce death or major disability, although there may be improved functional outcomes with intensive blood-pressure lowering.

Citation: Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355-2365.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Perioperative SSRI use associated with adverse surgical outcomes
2. Copper-surfaced rooms reduce health-care-acquired infections
3. Glucocorticoid therapy for five days not inferior to 14 days for COPD exacerbation
4. Patient preference for participation in medical decision-making may be associated with increased resource utilization
5. Early parenteral nutrition in critically ill adults does not significantly affect mortality or infection rates
6. Aggressive fluid and sodium restriction in acute decompensated heart failure did not improve outcomes
7. Lower rate of pacemaker, defibrillator device-pocket hematoma without anticoagulation interruption
8. Prophylactic penicillin decreased risk of recurrent leg cellulitis
9. Universal ICU decolonization reduced rates of mrsa clinical isolates and bloodstream infection
10. Intensive blood-pressure lowering in intracerebral hemorrhage did not reduce death or severe disability

Perioperative SSRI Use Associated with Adverse Surgical Outcomes

Clinical question: Does selective serotonin reuptake inhibitor (SSRI) use during hospitalization for surgery increase the risk of adverse perioperative outcomes?

Background: SSRIs commonly are prescribed but are associated with a small but higher risk for hemorrhage, arrhythmia, and sudden death. Single-site studies have described an association between SSRIs and adverse perioperative outcomes, but larger studies utilizing a broad range of surgical cases are lacking.

Study design: Retrospective cohort study.

Setting: Three hundred hospitals concentrated in the Southern U.S.

Synopsis: Using the “Perspective” database, this study examined 530,416 patients age >18 years undergoing major elective surgery, 72,540 (13.7%) of whom received an SSRI. Regression analysis showed patients receiving an SSRI had higher odds of mortality (OR 1.2, 95% CI [1.07-1.36]), higher odds of 30-day readmission (OR 1.22 [1.18-1.26]), and higher odds for bleeding (1.09 [1.04-1.15]). When the analysis was restricted to only patients with a diagnosis of depression, a higher risk of bleeding and readmission persisted.

This study reaffirms an association but does not establish a causal relationship between SSRI use and adverse perioperative outcomes. SSRI use may be a surrogate for other factors, including more severe mood disorders, poorer functional status, or chronic pain. Additionally, no information has been provided as to optimal duration of withholding SSRIs preoperatively. As such, it may be premature for hospitalists involved in perioperative care to modify recommendations based on this study.

Bottom line: Perioperative SSRI use is associated with an increased risk of bleeding and 30-day readmission.

Citation: Auerbach AD, Vittinghoff E, Maselli J, et al. Perioperative use of selective serotonin reuptake inhibitors and risks for adverse outcomes of surgery. JAMA Intern Med. 2013;173(12):1075-1081.

Copper-Surfaced Rooms Reduce Health-Care-Acquired Infections

Clinical question: Can copper alloy surfaces in ICU rooms lower rates of health-care-acquired infections (HAIs)?

Background: Environmental contamination is a potential source of HAIs. Copper has intrinsic broad-spectrum antimicrobial properties. This study tests the efficacy copper-surfaced items in hospital rooms have in preventing HAIs.

Study design: Randomized controlled trial.

Setting: Medical ICUs at Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center in Charleston, and the Memorial Sloan Kettering Cancer Center in New York City.

Synopsis: Six hundred fifty ICU patients were randomized to receive care either in rooms with copper surfacing on commonly handled patient care objects or in traditional rooms. Patients were screened for methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) on admission. The proportion of patients that developed either an HAI and/or MRSA or VRE colonization was significantly lower among patients in rooms with the copper-surfaced items (0.071 vs. 0.128; P=0.02). The rate of HAIs alone was also lower in the rooms with the copper (0.034 vs. 0.081; P=0.013).

A potential limitation to this study is that the rooms with copper items appeared different than traditional rooms, and therefore might have changed the behavior of health-care workers. Further, it is unclear how much copper surfacing would be necessary on general wards, where patients are more mobile. Still, HAIs are associated with longer lengths of stay and higher 30-day readmission rates, so these encouraging results warrant additional investigation into antimicrobial copper-alloy surfaces.

Bottom line: Copper-surfaced objects reduce HAI rates in ICU patients.

Citation: Salgado CD, Sepkowitz, KA, John JF, et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol. 2013;34(5):479-486.

Glucocorticoid Therapy for Five Days Not Inferior to 14 Days for COPD Exacerbation

Clinical question: Do short-course glucocorticoids work as well as conventional long courses for COPD exacerbation?

Background: International guidelines advocate a seven- to 14-day treatment course with glucocorticoids for COPD exacerbation, but the optimal duration of treatment is not known, and there are potential risks associated with glucocorticoid exposure.

Study design: Randomized, noninferiority, multicenter trial.

Setting: Five Swiss teaching hospitals.

Synopsis: Three hundred fourteen patients presenting to the ED with acute COPD exacerbation and without a history of asthma were randomized to receive treatment with 40 mg prednisone daily for either five or 14 days in a placebo-controlled, double-blinded fashion. There was no significant difference in the primary endpoint of re-exacerbation within six months. Patients in the five-day glucocorticoid group compared with the 14-day group were exposed to significantly less glucocorticoid.

Bottom line: Treatment for five days with glucocorticoids was not inferior to 14 days for acute COPD exacerbations with regard to re-exacerbations within six months and resulted in less glucocorticoid exposure overall.

Citation: Leuppi JF, Schuetz P, Bingisser R, et al. Short-term vs. conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE Randomized Clinical Trial. JAMA. 2013;390(21):2223-2231.

Patient Preference for Participation in Medical Decision-Making May Be Associated with Increased Resource Utilization

Clinical question: Do patient preferences for participation in medical decision-making affect health-care utilization?

Background: Patient participation in medical decision-making has been associated with improved patient satisfaction and health outcomes. There is little evidence to support theories that patient preferences might decrease or increase health-care utilization.

Study design: Survey study in academic research setting.

Setting: University of Chicago Medical Center.

Synopsis: More than 21,700 patients admitted to a general internal-medicine service completed a survey that included questions regarding preferences about receiving medical information and participation in medical decision-making. Survey data were linked with administrative data, including length of stay and total hospitalization costs.

Most patients (96.3%) expressed interest in receiving information about their illness and treatment options, but the majority of patients (71.1%) also expressed a preference to leave medical decision-making to their physician. Patients who preferred to participate in medical decision-making had significantly longer hospital LOS and higher total hospitalization cost.

Bottom line: Participation in medical decision-making significantly increased LOS and total costs.

Citation: Tak HJ, Ruhnke GW, Meltzer DO. Association of patient preferences for participation in decision making with length of stay and costs among hospitalized patients. JAMA Intern Med. 2013;173(13):1195-1205. doi: 10.1001/jamainternmed.2013.6048.

Early Parenteral Nutrition in Critically Ill Adults Does Not Significantly Affect Mortality or Infection Rates

Clinical question: Does providing early parenteral nutrition to critically ill adults with short-term relative contraindications to early enteral nutrition affect outcomes?

Background: The appropriate use of parenteral nutrition in critically ill adults is controversial. A systematic review found that critically ill patients randomized to receive early parenteral nutrition had significantly lower mortality but increased infection rates compared with standard care. A large-scale randomized trial was necessary to confirm the results.

Study design: Multicenter, randomized, single-blinded, controlled trial.

Setting: ICUs in 31 tertiary-care and community hospitals in Australia and New Zealand.

Synopsis: Researchers randomized 1,372 critically ill adults with relative contraindications to early enteral nutrition upon admission to the ICU to receive early parenteral nutrition or standard care. Early parenteral nutrition was started an average of 44 minutes after randomization. Clinicians defined standard care, with most patients remaining unfed for 2.8 days after randomization. Results were analyzed by intention-to-treat analysis, and loss to follow-up was 1%.

There was no significant difference in the primary outcome of 60-day mortality. Early parenteral nutrition patients received significantly fewer days of invasive ventilation, but did not have shorter ICU or hospital stays. Early parenteral nutrition patients experienced significantly less muscle-wasting and fat loss. There was no significant difference in new infection rates.

Bottom line: Early parenteral nutrition in critically ill adults resulted in significantly fewer days of invasive mechanical ventilation but did not cause a significant difference in length of stay, infection rates, or 60-day mortality.

Citation: Doig GS, Simpson F, Sweetman EA, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition. JAMA. 2013;309(20): 2130-2138.

Aggressive Fluid and Sodium Restriction in Acute Decompensated Heart Failure Did Not Improve Outcomes

Clinical question: Does aggressive fluid and sodium restriction in acute decompensated heart failure (ADHF) result in increased weight loss, improved clinical stability, or decreased 30-day readmission rate?

Background: Fluid and sodium restriction are standard nonpharmacologic measures used in the management of ADHF in hospitalized patients, despite an absence of data to support their efficacy.

Study design: Randomized, controlled clinical trial with blinded outcome assessments.

Setting: A public teaching hospital in Brazil.

Synopsis: Seventy-five patients hospitalized with ADHF were randomized to receive aggressive fluid (800 mL/day) and sodium restriction (800 mg/day) or liberal intake (at least 2.5 L/day fluid, 3 to 5 g/day sodium). There were no significant between-group differences in diuretic administration. The primary outcomes of weight loss and clinical stability at three days were not significantly different between the groups. The heart-failure-specific readmission rate at 30 days was not significantly different between the groups. The aggressive restriction group had significantly worse thirst.

The study is limited by the small fraction of patients enrolled (9.2% of 813 screened) and homogenous population. Additional confirmatory trials likely are needed to change the standard of care, but this study demonstrated that aggressive fluid and sodium restriction does not benefit hospitalized patients with ADHF.

Bottom line: Aggressive fluid and sodium restriction in hospitalized patients with ADHF does not result in improved short-term weight loss, clinical stability, or decreased 30-day readmission rate, but it does cause significantly worse thirst.

Citation: Aliti GB, Rabelo ER, Clausell N, et al. Aggressive fluid and sodium restriction in acute decompensated heart failure. JAMA Intern Med. 2013;173(12):1058-1064.

Lower Rate of Pacemaker, Defibrillator Device-Pocket Hematoma without Anticoagulation Interruption

Clinical question: Is it safer to place a pacemaker or implantable cardioverter-defibrillator (ICD) while on therapeutic warfarin versus bridging with heparin/low-molecular-weight heparin (LMWH)?

Background: Current guidelines recommend bridging with heparin or LMWH for patients at high risk for thromboembolic events around the time of pacemaker or ICD placement, but it is associated with significant risk of device-pocket hematoma. Some centers place pacemakers and ICDs without interruption of warfarin. However, there are limited data to support the safety of this approach.

Study design: Multicenter, single-blinded, randomized, controlled trial.

Setting: Seventeen centers in Canada and one center in Brazil.

Synopsis: Patients with a predicted annual risk of 5% of thromboembolism were randomized to continue anticoagulation with warfarin (median INR 2.3) or to bridge therapy with heparin or LMWH; they then evaluated the incidence of clinically significant hematoma requiring prolonged hospitalization, interruption of anticoagulation therapy, or further surgical intervention. After reviewing the data on 668 patients, the Data and Safety Monitoring Board recommended termination of the study given a significantly lower rate of device-pocket hematoma in the warfarin group (3.5%) compared with the bridge group (16%) with RR 0.19 (95% CI 0.10-0.36, P<0.001). Otherwise, major surgical and thromboembolic complications were rare and not significantly different in both groups.

Bottom line: Continued warfarin therapy was associated with significantly reduced incidence of device-pocket hematoma compared with bridge with heparin or LMWH.

Citation: Birnie DH, Healey JS, Wells GA, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013;368(22):2084-2093.

Prophylactic Penicillin Decreased Risk of Recurrent Leg Cellulitis

Clinical question: Does prophylactic, low-dose penicillin prevent recurrent cellulitis in patients with a history of two or more episodes of cellulitis?

Background: Some guidelines recommend prophylactic antibiotics for recurrent leg cellulitis, but there is no large randomized trial to support this practice, and clinical opinion is mixed.

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

Setting: Twenty-eight hospitals in the United Kingdom and Ireland.

Synopsis: Researchers randomized 274 patients with recurrent episodes of leg cellulitis (at least two episodes within the previous three years) to low-dose penicillin (250 mg) or placebo for 12 months and followed them for more than three years. During the prophylactic period, the penicillin group had a 45% reduction in the risk of a repeat cellulitis as compared to placebo (22% vs. 37%), equivalent to a number needed to treat to prevent a first recurrent cellulitis of five. The number of repeat episodes of cellulitis was lower overall in penicillin compared with the placebo group (119 vs. 164, P=0.02), although no significant difference was noted during the three-year follow-up period.

Factors associated with prophylaxis failure included three or more previous episodes of cellulitis, body mass index of 33 kg/m² or higher, and the presence of edema. No significant difference in adverse events was noted between the groups. Complete follow-up data was not available for participants during the follow-up period. Further study is needed to assess the long-term adverse effects and the duration of prophylaxis needed.

Bottom line: Prophylactic penicillin was effective in preventing recurrent leg cellulitis without increasing adverse effects, but its protective effect gradually declined once discontinued.

Citation: Thomas KS, Crook AM, Nunn AJ, et al. Penicillin to prevent recurrent leg cellulitis. N Engl J Med. 2013;368(18):1695-1703.

Universal ICU Decolonization Reduced Rates of MRSA Clinical Isolates and Bloodstream Infection

Clinical question: What is the most effective decolonization strategy for reducing methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens in ICUs?

Background: Studies have shown that daily chlorhexidine bathing of all patients in ICUs reduced MRSA acquisition and bloodstream infection from all pathogens. However, this universal strategy has not been compared to MRSA screening and contact precautions alone, or to targeted decolonization of MRSA carriers.

Study design: Cluster-randomized comparative-effectiveness trial.

Setting: Adult ICUs in 43 Hospital Corporation of America (HCA) hospitals in 16 states.

Synopsis: All adult ICUs in a given hospital were randomized to one of three infection prevention strategies: Group 1 continued MRSA screening and isolation; Group 2 performed screening, isolation, and decolonization of MRSA carriers; and Group 3 implemented universal decolonization with intranasal mupirocin and daily bathing with chlorhexidine-impregnated cloths but no screening.

Forty-three hospitals, including 74 ICUs and 74,256 patients, underwent randomization. Significant reductions in the primary outcome of ICU-attributable MRSA clinical isolates (excluding MRSA screening tests) and the secondary outcome of bloodstream infection due to any pathogen were demonstrated across the three groups. One bloodstream infection was prevented for every 54 patients who underwent decolonization. Formal cost-effectiveness analysis was not performed.

Bottom line: In the ICU, universal decolonization was more effective than screening and isolation or targeted decolonization in the reduction of clinical MRSA isolates and bloodstream infection due to any pathogen, although monitoring for emerging resistance is necessary.

Citation: Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-2265.

Intensive Blood-Pressure Lowering in Intracerebral Hemorrhage Did Not Reduce Death or Severe Disability

Clinical question: What is the efficacy and safety of early intensive blood-pressure lowering in patients with acute intracerebral hemorrhage?

Background: After intracerebral hemorrhage, blood pressure often becomes elevated and is a predictor of outcome. It is not known whether rapid lowering of blood pressure would improve outcome.

Study design: International, multicenter, prospective, randomized, open-treatment, blinded end-point trial.

Setting: One hundred forty-four hospitals in 21 countries.

Synopsis: Researchers randomly assigned 2,839 patients with intracerebral hemorrhage in the previous six hours to intensive blood-pressure lowering with target systolic blood pressure of <140 mmHg within one hour, or guideline-recommended treatment with target systolic blood pressure of <180 mmHg. The mean systolic blood pressure achieved was 150 mmHg in the intensive-treatment group and 164 mmHg in the standard-treatment group.

There was no significant difference between the two groups in the primary outcome of death or major disability. A pre-specified ordinal analysis of modified Rankin score (score of 0 indicates no symptoms; a score of 5 indicates severe disability) did show significantly lower modified Rankin scores with intensive treatment. There was no difference between the two groups in the rate of serious adverse events.

Bottom line: Early intensive blood-pressure lowering in patients with acute intracerebral hemorrhage did not reduce death or major disability, although there may be improved functional outcomes with intensive blood-pressure lowering.

Citation: Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355-2365.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

Citation:Mueller SK, Sponsler KC, Kripalani S, et al. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

Citation:Mueller SK, Sponsler KC, Kripalani S, et al. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

Citation:Mueller SK, Sponsler KC, Kripalani S, et al. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

Citation:Mueller SK, Sponsler KC, Kripalani S, et al. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

Citation:Mueller SK, Sponsler KC, Kripalani S, et al. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

Citation:Mueller SK, Sponsler KC, Kripalani S, et al. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Read more of our physician reviews of recent, HM-relevant literature.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
2. Radiation exposure in integrated healthcare systems, 1996-2010
3. Postoperative troponin predicts 30-day mortality
4. Clinical prediction model of mortality in acute heart failure
5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
6. Early surgery for high-risk, native-valve endocarditis patients
7. Risk factors after ED visit for syncope
8. Acute hyperglycemia in CAP patients
9. Hospital delirium associated with cognitive decline, institutionalization, and death
10. Seven-day ciprofloxacin effective against acute pyelonephritis
11. Advance directives in community patients with heart failure
12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
13. Simulation training improves lumbar puncture skills
14. PCP referrals to hospitals and publicly reported data
15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

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

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

Study design: Prospective, three-phase study.

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

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

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

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

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

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

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
2. Radiation exposure in integrated healthcare systems, 1996-2010
3. Postoperative troponin predicts 30-day mortality
4. Clinical prediction model of mortality in acute heart failure
5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
6. Early surgery for high-risk, native-valve endocarditis patients
7. Risk factors after ED visit for syncope
8. Acute hyperglycemia in CAP patients
9. Hospital delirium associated with cognitive decline, institutionalization, and death
10. Seven-day ciprofloxacin effective against acute pyelonephritis
11. Advance directives in community patients with heart failure
12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
13. Simulation training improves lumbar puncture skills
14. PCP referrals to hospitals and publicly reported data
15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

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

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

Study design: Prospective, three-phase study.

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

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

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

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

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

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

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
2. Radiation exposure in integrated healthcare systems, 1996-2010
3. Postoperative troponin predicts 30-day mortality
4. Clinical prediction model of mortality in acute heart failure
5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
6. Early surgery for high-risk, native-valve endocarditis patients
7. Risk factors after ED visit for syncope
8. Acute hyperglycemia in CAP patients
9. Hospital delirium associated with cognitive decline, institutionalization, and death
10. Seven-day ciprofloxacin effective against acute pyelonephritis
11. Advance directives in community patients with heart failure
12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
13. Simulation training improves lumbar puncture skills
14. PCP referrals to hospitals and publicly reported data
15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

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

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

Study design: Prospective, three-phase study.

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

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

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

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

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

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

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

Clinical question: What is the optimal duration of oral ciprofloxacin in women with acute community-acquired pyelonephritis?

Background: Despite being a commonly encountered infection, there are little data on the appropriate duration of therapy for acute pyelonephritis in women.

Study design: Prospective, randomized, open-labeled, double-blinded, noninferiority trial.

Setting: Twenty-one infectious diseases centers in Sweden.

Synopsis: Two hundred forty-eight women aged 18 or older with a presumed diagnosis of pyelonephritis were randomized to treatment with seven or 14 days of oral ciprofloxacin 500 mg twice daily. One hundred fifty-six per protocol patients were analyzed, and short-term clinical cure was shown to be noninferior, with cure of 97% in the seven-day group and 96% in the 14-day group (90% confidence interval -6.5-4.8, P=0.004). Results were also shown to be valid for older women and those with more severe infections. With growing concerns of antibiotic resistance and adverse drug events, using shorter courses of antibiotics has come into favor. The authors warn that these findings should not be extrapolated to other classes of antibiotics.

Bottom line: Treatment of community-acquired acute pyelonephritis in women with ciprofloxacin 500 mg twice daily for seven days is not inferior to 14 days.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012; Jun 20: [Epub ahead of print].

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What is the optimal duration of oral ciprofloxacin in women with acute community-acquired pyelonephritis?

Background: Despite being a commonly encountered infection, there are little data on the appropriate duration of therapy for acute pyelonephritis in women.

Study design: Prospective, randomized, open-labeled, double-blinded, noninferiority trial.

Setting: Twenty-one infectious diseases centers in Sweden.

Synopsis: Two hundred forty-eight women aged 18 or older with a presumed diagnosis of pyelonephritis were randomized to treatment with seven or 14 days of oral ciprofloxacin 500 mg twice daily. One hundred fifty-six per protocol patients were analyzed, and short-term clinical cure was shown to be noninferior, with cure of 97% in the seven-day group and 96% in the 14-day group (90% confidence interval -6.5-4.8, P=0.004). Results were also shown to be valid for older women and those with more severe infections. With growing concerns of antibiotic resistance and adverse drug events, using shorter courses of antibiotics has come into favor. The authors warn that these findings should not be extrapolated to other classes of antibiotics.

Bottom line: Treatment of community-acquired acute pyelonephritis in women with ciprofloxacin 500 mg twice daily for seven days is not inferior to 14 days.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012; Jun 20: [Epub ahead of print].

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What is the optimal duration of oral ciprofloxacin in women with acute community-acquired pyelonephritis?

Background: Despite being a commonly encountered infection, there are little data on the appropriate duration of therapy for acute pyelonephritis in women.

Study design: Prospective, randomized, open-labeled, double-blinded, noninferiority trial.

Setting: Twenty-one infectious diseases centers in Sweden.

Synopsis: Two hundred forty-eight women aged 18 or older with a presumed diagnosis of pyelonephritis were randomized to treatment with seven or 14 days of oral ciprofloxacin 500 mg twice daily. One hundred fifty-six per protocol patients were analyzed, and short-term clinical cure was shown to be noninferior, with cure of 97% in the seven-day group and 96% in the 14-day group (90% confidence interval -6.5-4.8, P=0.004). Results were also shown to be valid for older women and those with more severe infections. With growing concerns of antibiotic resistance and adverse drug events, using shorter courses of antibiotics has come into favor. The authors warn that these findings should not be extrapolated to other classes of antibiotics.

Bottom line: Treatment of community-acquired acute pyelonephritis in women with ciprofloxacin 500 mg twice daily for seven days is not inferior to 14 days.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012; Jun 20: [Epub ahead of print].

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What is the prognostic influence of atrial fibrillation in patients with acute myocardial infarction?

Background: There have been conflicting reports regarding the prognostic impact of atrial fibrillation (AF) in patients with acute myocardial infarction (MI). This study represents the first meta-analysis performed to quantify the mortality risk associated with AF in MI patients.

Study design: Meta-analysis of observational studies.

Setting: Forty-three studies involving 278,854 patients diagnosed with MI from 1972 to 2000.

Synopsis: The odds ratio (OR) of mortality associated with AF in MI patients was 1.46 (95% confidence interval, 1.35 to 1.58, I2=76%, 23 studies). Although there was significant heterogeneity in included studies, in subgroup analysis, the significant association between AF and mortality was present whether the AF was new (defined as occurring for the first time within one week of MI) with OR of 1.37 (95% confidence interval, 1.26 to 1.49; I2=28%, nine studies) or old (defined as pre-existing before the MI admission) with OR of 1.28 (95% confidence interval, 1.16 to 1.40, I2=24%, four studies). Sensitivity analyses performed by pooling studies according to follow-up duration and adjustment for confounding clinical factors had little effect on the estimates.

Bottom line: AF was associated with increased mortality in patients with MI regardless of the timing of AF development.

Citation: Jabre P, Roger VL, Murad MH, et al. Mortality associated with atrial fibrillation in patients with myocardial infarction. Circulation. 2011;123:1587-1593.

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

Clinical question: What is the prognostic influence of atrial fibrillation in patients with acute myocardial infarction?

Background: There have been conflicting reports regarding the prognostic impact of atrial fibrillation (AF) in patients with acute myocardial infarction (MI). This study represents the first meta-analysis performed to quantify the mortality risk associated with AF in MI patients.

Study design: Meta-analysis of observational studies.

Setting: Forty-three studies involving 278,854 patients diagnosed with MI from 1972 to 2000.

Synopsis: The odds ratio (OR) of mortality associated with AF in MI patients was 1.46 (95% confidence interval, 1.35 to 1.58, I2=76%, 23 studies). Although there was significant heterogeneity in included studies, in subgroup analysis, the significant association between AF and mortality was present whether the AF was new (defined as occurring for the first time within one week of MI) with OR of 1.37 (95% confidence interval, 1.26 to 1.49; I2=28%, nine studies) or old (defined as pre-existing before the MI admission) with OR of 1.28 (95% confidence interval, 1.16 to 1.40, I2=24%, four studies). Sensitivity analyses performed by pooling studies according to follow-up duration and adjustment for confounding clinical factors had little effect on the estimates.

Bottom line: AF was associated with increased mortality in patients with MI regardless of the timing of AF development.

Citation: Jabre P, Roger VL, Murad MH, et al. Mortality associated with atrial fibrillation in patients with myocardial infarction. Circulation. 2011;123:1587-1593.

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

Clinical question: What is the prognostic influence of atrial fibrillation in patients with acute myocardial infarction?

Background: There have been conflicting reports regarding the prognostic impact of atrial fibrillation (AF) in patients with acute myocardial infarction (MI). This study represents the first meta-analysis performed to quantify the mortality risk associated with AF in MI patients.

Study design: Meta-analysis of observational studies.

Setting: Forty-three studies involving 278,854 patients diagnosed with MI from 1972 to 2000.

Synopsis: The odds ratio (OR) of mortality associated with AF in MI patients was 1.46 (95% confidence interval, 1.35 to 1.58, I2=76%, 23 studies). Although there was significant heterogeneity in included studies, in subgroup analysis, the significant association between AF and mortality was present whether the AF was new (defined as occurring for the first time within one week of MI) with OR of 1.37 (95% confidence interval, 1.26 to 1.49; I2=28%, nine studies) or old (defined as pre-existing before the MI admission) with OR of 1.28 (95% confidence interval, 1.16 to 1.40, I2=24%, four studies). Sensitivity analyses performed by pooling studies according to follow-up duration and adjustment for confounding clinical factors had little effect on the estimates.

Bottom line: AF was associated with increased mortality in patients with MI regardless of the timing of AF development.

Citation: Jabre P, Roger VL, Murad MH, et al. Mortality associated with atrial fibrillation in patients with myocardial infarction. Circulation. 2011;123:1587-1593.

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

In This Edition

Literature At A Glance

A guide to this month’s studies

1. PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study
2. CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction
3. Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia
4. CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation
5. Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer
6. MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections
7. New Left Bundle Branch Block Does Not Predict MI
8. Acute Beta-Blocker Therapy for MI Increased Risk of Shock

PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study

Clinical question: Is percutaneous coronary intervention (PCI) an acceptable alternative to coronary artery bypass grafting (CABG) in unprotected left main coronary artery disease (CAD)?

Background: The current standard of care for unprotected left main CAD is CABG. A sub-study from a large randomized trial suggests that PCI might be an alternative to CABG for patients with left main CAD. Outcomes after the two treatments have not been directly compared in an appropriately powered trial.

Study design: Prospective, open-label, randomized trial powered for noninferiority.

Setting: Thirteen sites in South Korea.

Synopsis: Six hundred patients with newly diagnosed left main disease with >50% stenosis were randomized to PCI with a sirolimus-eluting stent versus CABG. The primary endpoint of major adverse cardiac or cerebrovascular events occurred in 8.7% in the PCI group and 6.7% in the CABG group at one year (absolute risk difference 2 percentage points, 95% CI, -1.6 to 5.6; P=0.01), which was considered noninferior.

However, ischemia-driven target-vessel revascularization occurred in significantly more patients in the PCI group than in the CABG group. The wide noninferiority margin was due to an unexpectedly low rate of events, thus underpowering the study. Also, study duration was only two years.

Bottom line: PCI with a sirolimus-eluting stent was noninferior to CABG for unprotected left main CAD in this study, but the wide noninferiority margin and limited follow-up duration limit clinical application.

Reference: Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718-1727.

CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction

Clinical question: What role does coronary-artery bypass grafting (CABG) have in the treatment of patients with both coronary artery disease (CAD) and heart failure?

Background: Although CAD is the most common cause of heart failure, early trials that evaluated the use of CABG in relieving angina excluded patients who had left ventricular (LV) dysfunction with ejection fraction <35%. It is unknown whether CABG adds mortality benefit to intensive medical treatment in patients with CAD and LV dysfunction.

Study design: Multicenter, nonblinded, randomized trial.

Setting: One hundred twenty-seven sites in 26 countries.

Synopsis: From July 2002 to May 2007, 1,212 patients with known CAD amenable to CABG and LV ejection fraction <35% were randomized to medical therapy alone versus CABG plus medical therapy with an average follow-up of five years. The primary outcome of death from any cause occurred in 41% of the medical-therapy-alone group and 36% of the CABG-plus-medical-therapy group (hazard ratio with CABG 0.86; 95% CI 0.72 to 1.04; P=0.12).

Despite subgroup analysis suggesting decreased death rates from cardiovascular causes in the latter group, there was no significant difference in the primary endpoint of death from any cause.

Bottom line: The addition of CABG to medical therapy for patients with CAD and left ventricular dysfunction does not decrease mortality.

Reference: Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616.

Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia

Clinical question: Is linezolid superior to glycopeptide antibiotics in the treatment of nosocomial pneumonia?

Background: Current ATS/IDSA guidelines suggest that linezolid might be preferred over glycopeptide antibiotics (i.e. vancomycin and teicoplanin) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although this recommendation is based on a retrospective subgroup analysis of one randomized trial. No systematic reviews have looked at the comparative efficacy and safety of linezolid and glycopeptide antibiotics for nosocomial pneumonia.

Study design: Meta-analysis using a highly sensitive search method.

Setting: Eight multicenter, randomized controlled trials (RCTs).

Synopsis: The study authors retrieved 762 articles with a highly sensitive search strategy, from which eight RCTs were identified that met study criteria for a total of 1,641 patients. Primary outcome of clinical success at test-of-cure was not different between the two classes of antibiotics (pooled RR 1.04, 95% CI 0.97-1.11, P=0.28). Other endpoints, including mortality and microbiologic eradication, were similar between the two groups.

Clinical success in the subgroup of patients with culture-confirmed MRSA pneumonia was not different than those without culture-proven MRSA, although the study was not powered for subgroup analysis. Risk of thrombocytopenia and renal impairment were not statistically different in the limited subgroup of trials reporting this data.

The results should not be generalized to community-acquired MRSA or MRSA pneumonia with characteristics of PVL toxin-producing strain.

Bottom line: For the treatment of nosocomial pneumonia, there was no significant difference in clinical success or mortality between linezolid and glycopeptide antibiotics.

Citation: Walkey AJ, O’Donnell MR, Weiner RS. Linezolid vs. glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2011;139: 1148-1155.

CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation

Clinical question: Are biomarkers such as CRP or procalcitonin useful in differentiating pneumonia from asthma or COPD exacerbation in hospitalized patients?

Background: Antibiotic overuse is associated with the emergence of drug resistance. One potential strategy to decrease antibiotic overuse is biomarker-guided therapy. Several randomized controlled trials (RCT) with procalcitonin-guided therapy have resulted in reduced antibiotic use for symptoms of acute respiratory tract infections (RTI). The use of CRP as a biomarker in acute RTI is not as well-described.

Study design: Prospective, observational, diagnostic accuracy study.

Setting: Winter months, 2006 to 2008, in two hospitals in England.

Synopsis: The study examined 319 patients: 62 with pneumonia, 96 with asthma exacerbation, and 161 with COPD exacerbation. Patients with pneumonia had significantly higher procalcitonin and CRP levels than those with COPD (P<0.0001) or asthma (P<0.0001). The area under receiver operator characteristic curve for distinguishing between pneumonia (requiring antibiotics) and asthma exacerbation (not requiring antibiotics) was 0.93 (0.88-0.98) for procalcitonin and 0.96 (0.93-1.00) for CRP. A CRP value >48 mg/L had a sensitivity of 91% (95% CI 80%-97%) and specificity of 93% (95% CI 86-98).

Using this CRP threshold, antibiotic use would have been reduced by 88% in asthma exacerbation, 76% in COPD exacerbation, and 9% in pneumonia cases.

This strategy was developed in a single-center study and requires further validation in a multicenter RCT.

Bottom line: Procalcitonin and CRP were elevated in patients with pneumonia compared to patients with asthma or COPD exacerbation and might be useful in guiding antibiotic usage.

Citation: Bafadhel, M, Clark TW, Reid, C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. 2011;139:1410-1418.

Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer

Clinical question: How does FOLFIRINOX compare to gemcitabine as first-line treatment of metastatic pancreatic cancer?

Background: Single-agent gemcitabine is the standard first-line treatment for metastatic pancreatic cancer. Preclinical studies followed by Phase 1 and Phase 2 studies have demonstrated response to the oxaliplatin, irinotecan, leucovorin, and fluorouracil regimen (FOLFIRINOX).

Study design: Multicenter, randomized, controlled Phase 2-3 trial.

Setting: Fifteen centers in France during Phase 2, which then expanded to 48 centers for Phase 3.

Synopsis: Three hundred forty-two patients with good performance status (ECOG 0 or 1) and age <76 were randomized to receive FOLFIRINOX or gemcitabine. Median survival in the FOLFIRINOX group was significantly increased, at 11.1 months, compared with 6.8 months in the gemcitabine group (HR 0.57, CI 95%, 0.45-0.73, P<000.1).

Median progression-free survival, objective response rate, and quality of life score at six months were significantly increased in the FOLFIRINOX group. Significantly more grade 3 or grade 4 toxicity was reported in the FOLFIRINOX group.

Patients with elevated bilirubin were excluded due to increased risk of irinotecan-induced toxicity, resulting in only 38% of study patients with carcinoma of the pancreatic head and low proportion of enrolled patients (14.3%) with biliary stents.

Bottom line: FOLFIRONOX was associated with a significant survival advantage compared with single-agent gemcitabine in carefully selected patients with advanced pancreatic cancer, although it was associated with increased toxicity.

Citation: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.

MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections

Clinical question: Can nationwide implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, influence healthcare-associated MRSA infection rates?

Background: MRSA is a common cause of nosocomial infection. A pilot project at a single Veterans Affairs (VA) hospital utilized a “MRSA bundle” developed from published guidelines, which resulted in decreased healthcare-associated MRSA infections. In October 2007, the MRSA bundle was implemented throughout VA hospitals nationwide.

Study design: Quality-improvement (QI) observational initiative.

Setting: One hundred fifty-eight acute-care VA hospitals in the U.S.

Synopsis: From October 2007 to June 2010, there were 1,934,598 admissions, transfers, or discharges, and 8,318,675 patient-days. Of this study group, 96% of patients were screened at admission and 93% were screened at transfer or discharge. MRSA colonization or infection at the time of admission was 13.6%. Rates of healthcare-associated MRSA infection declined 45% in the non-ICU setting (0.47 to 0.26 per 1,000 patient-days, P<0.001) and 62% in the ICU setting (1.64 to 0.62 per 1,000 patient days, P<0.001).

It is unclear how much each individual component of the MRSA bundle impacted the declining MRSA infection rate.

Bottom line: Implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, decreased the healthcare-associated MRSA infection rate in a large hospital system.

Citation: Jain R, Kralovi S, Evans M, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-1430.

New Left Bundle Branch Block Does Not Predict MI

Clinical question: How does the chronicity of left bundle branch block (LBBB) impact diagnosis and outcome in patients undergoing evaluation for acute myocardial infarction (MI)?

Background: ACA/AHA guidelines recommend that patients with new or presumed new LBBB undergo early reperfusion therapy. However, previous studies have shown that a minority of patients with new LBBB are diagnosed with MI.

Study design: Prospective cohort study.

Setting: University hospital in the U.S.

Synopsis: From 1994 to 2009, 401 consecutive patients undergoing evaluation for acute coronary syndrome with LBBB on initial ECG were included in the analysis. Of these patients, 64% had new (37%) or presumably new (27%) LBBB. Twenty-nine percent were diagnosed with MI, but there was no difference in frequency or size of MI between the new, presumably new, or chronic LBBB groups.

Concordant ST-T changes were an independent predictor of MI (OR 17, 95% CI 3.4-81, P<0.001) and mortality (OR 4.3, 95% CI 1.3-15, P<0.001), although this finding was present in only about 11% of the patient group.

Bottom line: Left bundle branch block is not a predictor of MI, although concordant ST-T changes were an independent predictor of MI and mortality.

Citation: Kontos MC, Aziz HA, Chau VQ, et al. Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction. Am Heart J. 2011;161(4):698-704.

Acute Beta-Blocker Therapy for MI Increased Risk of Shock

Clinical question: How does acute beta-blocker therapy in myocardial infarction (MI) impact outcome?

Background: Long-term treatment with beta-blockers after myocardial infarction (MI) reduces mortality. However, data regarding outcome after acute use of beta-blockers in the first 24 hours of MI is conflicting. Updated ACA/AHA guidelines for STEMI and NSTEMI recommend caution when using beta-blockers in the first 24 hours, particularly in patients at risk for shock.

Study design: Observational registry study.

Setting: Two hundred ninety-one U.S hospitals.

Synopsis: More than 34,600 patients diagnosed with STEMI and NSTEMI from January 2007 to June 2008 were identified from a national QI MI registry. Patients were stratified by guideline-stated risk factors for shock; age >70, HR >110, and systolic BP <120 were associated with increased risk of composite outcome of shock or death.

At least one high-risk factor was present in 63% of the NSTEMI patients and 45% of STEMI patients; however, >90% of these patients received acute beta-blocker therapy. Nearly half (49%) of the NSTEMI patients received beta-blockers in the ED and 62% of the STEMI patients received beta-blockers before PCI.

In a multivariable model, NSTEMI patients receiving beta-blocker therapy in the ED were more likely to develop cardiogenic shock (OR 1.54, 95% CI 1.26-1.88, P<.001), as were STEMI patients receiving beta-blocker therapy prior to PCI (1.40, 95% CI 1.10-1.79, P=.006).

Bottom line: Caution should be exercised when using beta-blocker therapy during acute MI, particularly in the ED or prior to primary PCI.

Citation: Kontos MC, Diercks DB, Ho MP, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology’s NCDR. Am Heart J. 2011;161(5):864-870.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study
2. CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction
3. Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia
4. CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation
5. Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer
6. MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections
7. New Left Bundle Branch Block Does Not Predict MI
8. Acute Beta-Blocker Therapy for MI Increased Risk of Shock

PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study

Clinical question: Is percutaneous coronary intervention (PCI) an acceptable alternative to coronary artery bypass grafting (CABG) in unprotected left main coronary artery disease (CAD)?

Background: The current standard of care for unprotected left main CAD is CABG. A sub-study from a large randomized trial suggests that PCI might be an alternative to CABG for patients with left main CAD. Outcomes after the two treatments have not been directly compared in an appropriately powered trial.

Study design: Prospective, open-label, randomized trial powered for noninferiority.

Setting: Thirteen sites in South Korea.

Synopsis: Six hundred patients with newly diagnosed left main disease with >50% stenosis were randomized to PCI with a sirolimus-eluting stent versus CABG. The primary endpoint of major adverse cardiac or cerebrovascular events occurred in 8.7% in the PCI group and 6.7% in the CABG group at one year (absolute risk difference 2 percentage points, 95% CI, -1.6 to 5.6; P=0.01), which was considered noninferior.

However, ischemia-driven target-vessel revascularization occurred in significantly more patients in the PCI group than in the CABG group. The wide noninferiority margin was due to an unexpectedly low rate of events, thus underpowering the study. Also, study duration was only two years.

Bottom line: PCI with a sirolimus-eluting stent was noninferior to CABG for unprotected left main CAD in this study, but the wide noninferiority margin and limited follow-up duration limit clinical application.

Reference: Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718-1727.

CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction

Clinical question: What role does coronary-artery bypass grafting (CABG) have in the treatment of patients with both coronary artery disease (CAD) and heart failure?

Background: Although CAD is the most common cause of heart failure, early trials that evaluated the use of CABG in relieving angina excluded patients who had left ventricular (LV) dysfunction with ejection fraction <35%. It is unknown whether CABG adds mortality benefit to intensive medical treatment in patients with CAD and LV dysfunction.

Study design: Multicenter, nonblinded, randomized trial.

Setting: One hundred twenty-seven sites in 26 countries.

Synopsis: From July 2002 to May 2007, 1,212 patients with known CAD amenable to CABG and LV ejection fraction <35% were randomized to medical therapy alone versus CABG plus medical therapy with an average follow-up of five years. The primary outcome of death from any cause occurred in 41% of the medical-therapy-alone group and 36% of the CABG-plus-medical-therapy group (hazard ratio with CABG 0.86; 95% CI 0.72 to 1.04; P=0.12).

Despite subgroup analysis suggesting decreased death rates from cardiovascular causes in the latter group, there was no significant difference in the primary endpoint of death from any cause.

Bottom line: The addition of CABG to medical therapy for patients with CAD and left ventricular dysfunction does not decrease mortality.

Reference: Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616.

Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia

Clinical question: Is linezolid superior to glycopeptide antibiotics in the treatment of nosocomial pneumonia?

Background: Current ATS/IDSA guidelines suggest that linezolid might be preferred over glycopeptide antibiotics (i.e. vancomycin and teicoplanin) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although this recommendation is based on a retrospective subgroup analysis of one randomized trial. No systematic reviews have looked at the comparative efficacy and safety of linezolid and glycopeptide antibiotics for nosocomial pneumonia.

Study design: Meta-analysis using a highly sensitive search method.

Setting: Eight multicenter, randomized controlled trials (RCTs).

Synopsis: The study authors retrieved 762 articles with a highly sensitive search strategy, from which eight RCTs were identified that met study criteria for a total of 1,641 patients. Primary outcome of clinical success at test-of-cure was not different between the two classes of antibiotics (pooled RR 1.04, 95% CI 0.97-1.11, P=0.28). Other endpoints, including mortality and microbiologic eradication, were similar between the two groups.

Clinical success in the subgroup of patients with culture-confirmed MRSA pneumonia was not different than those without culture-proven MRSA, although the study was not powered for subgroup analysis. Risk of thrombocytopenia and renal impairment were not statistically different in the limited subgroup of trials reporting this data.

The results should not be generalized to community-acquired MRSA or MRSA pneumonia with characteristics of PVL toxin-producing strain.

Bottom line: For the treatment of nosocomial pneumonia, there was no significant difference in clinical success or mortality between linezolid and glycopeptide antibiotics.

Citation: Walkey AJ, O’Donnell MR, Weiner RS. Linezolid vs. glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2011;139: 1148-1155.

CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation

Clinical question: Are biomarkers such as CRP or procalcitonin useful in differentiating pneumonia from asthma or COPD exacerbation in hospitalized patients?

Background: Antibiotic overuse is associated with the emergence of drug resistance. One potential strategy to decrease antibiotic overuse is biomarker-guided therapy. Several randomized controlled trials (RCT) with procalcitonin-guided therapy have resulted in reduced antibiotic use for symptoms of acute respiratory tract infections (RTI). The use of CRP as a biomarker in acute RTI is not as well-described.

Study design: Prospective, observational, diagnostic accuracy study.

Setting: Winter months, 2006 to 2008, in two hospitals in England.

Synopsis: The study examined 319 patients: 62 with pneumonia, 96 with asthma exacerbation, and 161 with COPD exacerbation. Patients with pneumonia had significantly higher procalcitonin and CRP levels than those with COPD (P<0.0001) or asthma (P<0.0001). The area under receiver operator characteristic curve for distinguishing between pneumonia (requiring antibiotics) and asthma exacerbation (not requiring antibiotics) was 0.93 (0.88-0.98) for procalcitonin and 0.96 (0.93-1.00) for CRP. A CRP value >48 mg/L had a sensitivity of 91% (95% CI 80%-97%) and specificity of 93% (95% CI 86-98).

Using this CRP threshold, antibiotic use would have been reduced by 88% in asthma exacerbation, 76% in COPD exacerbation, and 9% in pneumonia cases.

This strategy was developed in a single-center study and requires further validation in a multicenter RCT.

Bottom line: Procalcitonin and CRP were elevated in patients with pneumonia compared to patients with asthma or COPD exacerbation and might be useful in guiding antibiotic usage.

Citation: Bafadhel, M, Clark TW, Reid, C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. 2011;139:1410-1418.

Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer

Clinical question: How does FOLFIRINOX compare to gemcitabine as first-line treatment of metastatic pancreatic cancer?

Background: Single-agent gemcitabine is the standard first-line treatment for metastatic pancreatic cancer. Preclinical studies followed by Phase 1 and Phase 2 studies have demonstrated response to the oxaliplatin, irinotecan, leucovorin, and fluorouracil regimen (FOLFIRINOX).

Study design: Multicenter, randomized, controlled Phase 2-3 trial.

Setting: Fifteen centers in France during Phase 2, which then expanded to 48 centers for Phase 3.

Synopsis: Three hundred forty-two patients with good performance status (ECOG 0 or 1) and age <76 were randomized to receive FOLFIRINOX or gemcitabine. Median survival in the FOLFIRINOX group was significantly increased, at 11.1 months, compared with 6.8 months in the gemcitabine group (HR 0.57, CI 95%, 0.45-0.73, P<000.1).

Median progression-free survival, objective response rate, and quality of life score at six months were significantly increased in the FOLFIRINOX group. Significantly more grade 3 or grade 4 toxicity was reported in the FOLFIRINOX group.

Patients with elevated bilirubin were excluded due to increased risk of irinotecan-induced toxicity, resulting in only 38% of study patients with carcinoma of the pancreatic head and low proportion of enrolled patients (14.3%) with biliary stents.

Bottom line: FOLFIRONOX was associated with a significant survival advantage compared with single-agent gemcitabine in carefully selected patients with advanced pancreatic cancer, although it was associated with increased toxicity.

Citation: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.

MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections

Clinical question: Can nationwide implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, influence healthcare-associated MRSA infection rates?

Background: MRSA is a common cause of nosocomial infection. A pilot project at a single Veterans Affairs (VA) hospital utilized a “MRSA bundle” developed from published guidelines, which resulted in decreased healthcare-associated MRSA infections. In October 2007, the MRSA bundle was implemented throughout VA hospitals nationwide.

Study design: Quality-improvement (QI) observational initiative.

Setting: One hundred fifty-eight acute-care VA hospitals in the U.S.

Synopsis: From October 2007 to June 2010, there were 1,934,598 admissions, transfers, or discharges, and 8,318,675 patient-days. Of this study group, 96% of patients were screened at admission and 93% were screened at transfer or discharge. MRSA colonization or infection at the time of admission was 13.6%. Rates of healthcare-associated MRSA infection declined 45% in the non-ICU setting (0.47 to 0.26 per 1,000 patient-days, P<0.001) and 62% in the ICU setting (1.64 to 0.62 per 1,000 patient days, P<0.001).

It is unclear how much each individual component of the MRSA bundle impacted the declining MRSA infection rate.

Bottom line: Implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, decreased the healthcare-associated MRSA infection rate in a large hospital system.

Citation: Jain R, Kralovi S, Evans M, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-1430.

New Left Bundle Branch Block Does Not Predict MI

Clinical question: How does the chronicity of left bundle branch block (LBBB) impact diagnosis and outcome in patients undergoing evaluation for acute myocardial infarction (MI)?

Background: ACA/AHA guidelines recommend that patients with new or presumed new LBBB undergo early reperfusion therapy. However, previous studies have shown that a minority of patients with new LBBB are diagnosed with MI.

Study design: Prospective cohort study.

Setting: University hospital in the U.S.

Synopsis: From 1994 to 2009, 401 consecutive patients undergoing evaluation for acute coronary syndrome with LBBB on initial ECG were included in the analysis. Of these patients, 64% had new (37%) or presumably new (27%) LBBB. Twenty-nine percent were diagnosed with MI, but there was no difference in frequency or size of MI between the new, presumably new, or chronic LBBB groups.

Concordant ST-T changes were an independent predictor of MI (OR 17, 95% CI 3.4-81, P<0.001) and mortality (OR 4.3, 95% CI 1.3-15, P<0.001), although this finding was present in only about 11% of the patient group.

Bottom line: Left bundle branch block is not a predictor of MI, although concordant ST-T changes were an independent predictor of MI and mortality.

Citation: Kontos MC, Aziz HA, Chau VQ, et al. Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction. Am Heart J. 2011;161(4):698-704.

Acute Beta-Blocker Therapy for MI Increased Risk of Shock

Clinical question: How does acute beta-blocker therapy in myocardial infarction (MI) impact outcome?

Background: Long-term treatment with beta-blockers after myocardial infarction (MI) reduces mortality. However, data regarding outcome after acute use of beta-blockers in the first 24 hours of MI is conflicting. Updated ACA/AHA guidelines for STEMI and NSTEMI recommend caution when using beta-blockers in the first 24 hours, particularly in patients at risk for shock.

Study design: Observational registry study.

Setting: Two hundred ninety-one U.S hospitals.

Synopsis: More than 34,600 patients diagnosed with STEMI and NSTEMI from January 2007 to June 2008 were identified from a national QI MI registry. Patients were stratified by guideline-stated risk factors for shock; age >70, HR >110, and systolic BP <120 were associated with increased risk of composite outcome of shock or death.

At least one high-risk factor was present in 63% of the NSTEMI patients and 45% of STEMI patients; however, >90% of these patients received acute beta-blocker therapy. Nearly half (49%) of the NSTEMI patients received beta-blockers in the ED and 62% of the STEMI patients received beta-blockers before PCI.

In a multivariable model, NSTEMI patients receiving beta-blocker therapy in the ED were more likely to develop cardiogenic shock (OR 1.54, 95% CI 1.26-1.88, P<.001), as were STEMI patients receiving beta-blocker therapy prior to PCI (1.40, 95% CI 1.10-1.79, P=.006).

Bottom line: Caution should be exercised when using beta-blocker therapy during acute MI, particularly in the ED or prior to primary PCI.

Citation: Kontos MC, Diercks DB, Ho MP, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology’s NCDR. Am Heart J. 2011;161(5):864-870.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study
2. CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction
3. Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia
4. CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation
5. Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer
6. MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections
7. New Left Bundle Branch Block Does Not Predict MI
8. Acute Beta-Blocker Therapy for MI Increased Risk of Shock

PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study

Clinical question: Is percutaneous coronary intervention (PCI) an acceptable alternative to coronary artery bypass grafting (CABG) in unprotected left main coronary artery disease (CAD)?

Background: The current standard of care for unprotected left main CAD is CABG. A sub-study from a large randomized trial suggests that PCI might be an alternative to CABG for patients with left main CAD. Outcomes after the two treatments have not been directly compared in an appropriately powered trial.

Study design: Prospective, open-label, randomized trial powered for noninferiority.

Setting: Thirteen sites in South Korea.

Synopsis: Six hundred patients with newly diagnosed left main disease with >50% stenosis were randomized to PCI with a sirolimus-eluting stent versus CABG. The primary endpoint of major adverse cardiac or cerebrovascular events occurred in 8.7% in the PCI group and 6.7% in the CABG group at one year (absolute risk difference 2 percentage points, 95% CI, -1.6 to 5.6; P=0.01), which was considered noninferior.

However, ischemia-driven target-vessel revascularization occurred in significantly more patients in the PCI group than in the CABG group. The wide noninferiority margin was due to an unexpectedly low rate of events, thus underpowering the study. Also, study duration was only two years.

Bottom line: PCI with a sirolimus-eluting stent was noninferior to CABG for unprotected left main CAD in this study, but the wide noninferiority margin and limited follow-up duration limit clinical application.

Reference: Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718-1727.

CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction

Clinical question: What role does coronary-artery bypass grafting (CABG) have in the treatment of patients with both coronary artery disease (CAD) and heart failure?

Background: Although CAD is the most common cause of heart failure, early trials that evaluated the use of CABG in relieving angina excluded patients who had left ventricular (LV) dysfunction with ejection fraction <35%. It is unknown whether CABG adds mortality benefit to intensive medical treatment in patients with CAD and LV dysfunction.

Study design: Multicenter, nonblinded, randomized trial.

Setting: One hundred twenty-seven sites in 26 countries.

Synopsis: From July 2002 to May 2007, 1,212 patients with known CAD amenable to CABG and LV ejection fraction <35% were randomized to medical therapy alone versus CABG plus medical therapy with an average follow-up of five years. The primary outcome of death from any cause occurred in 41% of the medical-therapy-alone group and 36% of the CABG-plus-medical-therapy group (hazard ratio with CABG 0.86; 95% CI 0.72 to 1.04; P=0.12).

Despite subgroup analysis suggesting decreased death rates from cardiovascular causes in the latter group, there was no significant difference in the primary endpoint of death from any cause.

Bottom line: The addition of CABG to medical therapy for patients with CAD and left ventricular dysfunction does not decrease mortality.

Reference: Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616.

Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia

Clinical question: Is linezolid superior to glycopeptide antibiotics in the treatment of nosocomial pneumonia?

Background: Current ATS/IDSA guidelines suggest that linezolid might be preferred over glycopeptide antibiotics (i.e. vancomycin and teicoplanin) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although this recommendation is based on a retrospective subgroup analysis of one randomized trial. No systematic reviews have looked at the comparative efficacy and safety of linezolid and glycopeptide antibiotics for nosocomial pneumonia.

Study design: Meta-analysis using a highly sensitive search method.

Setting: Eight multicenter, randomized controlled trials (RCTs).

Synopsis: The study authors retrieved 762 articles with a highly sensitive search strategy, from which eight RCTs were identified that met study criteria for a total of 1,641 patients. Primary outcome of clinical success at test-of-cure was not different between the two classes of antibiotics (pooled RR 1.04, 95% CI 0.97-1.11, P=0.28). Other endpoints, including mortality and microbiologic eradication, were similar between the two groups.

Clinical success in the subgroup of patients with culture-confirmed MRSA pneumonia was not different than those without culture-proven MRSA, although the study was not powered for subgroup analysis. Risk of thrombocytopenia and renal impairment were not statistically different in the limited subgroup of trials reporting this data.

The results should not be generalized to community-acquired MRSA or MRSA pneumonia with characteristics of PVL toxin-producing strain.

Bottom line: For the treatment of nosocomial pneumonia, there was no significant difference in clinical success or mortality between linezolid and glycopeptide antibiotics.

Citation: Walkey AJ, O’Donnell MR, Weiner RS. Linezolid vs. glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2011;139: 1148-1155.

CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation

Clinical question: Are biomarkers such as CRP or procalcitonin useful in differentiating pneumonia from asthma or COPD exacerbation in hospitalized patients?

Background: Antibiotic overuse is associated with the emergence of drug resistance. One potential strategy to decrease antibiotic overuse is biomarker-guided therapy. Several randomized controlled trials (RCT) with procalcitonin-guided therapy have resulted in reduced antibiotic use for symptoms of acute respiratory tract infections (RTI). The use of CRP as a biomarker in acute RTI is not as well-described.

Study design: Prospective, observational, diagnostic accuracy study.

Setting: Winter months, 2006 to 2008, in two hospitals in England.

Synopsis: The study examined 319 patients: 62 with pneumonia, 96 with asthma exacerbation, and 161 with COPD exacerbation. Patients with pneumonia had significantly higher procalcitonin and CRP levels than those with COPD (P<0.0001) or asthma (P<0.0001). The area under receiver operator characteristic curve for distinguishing between pneumonia (requiring antibiotics) and asthma exacerbation (not requiring antibiotics) was 0.93 (0.88-0.98) for procalcitonin and 0.96 (0.93-1.00) for CRP. A CRP value >48 mg/L had a sensitivity of 91% (95% CI 80%-97%) and specificity of 93% (95% CI 86-98).

Using this CRP threshold, antibiotic use would have been reduced by 88% in asthma exacerbation, 76% in COPD exacerbation, and 9% in pneumonia cases.

This strategy was developed in a single-center study and requires further validation in a multicenter RCT.

Bottom line: Procalcitonin and CRP were elevated in patients with pneumonia compared to patients with asthma or COPD exacerbation and might be useful in guiding antibiotic usage.

Citation: Bafadhel, M, Clark TW, Reid, C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. 2011;139:1410-1418.

Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer

Clinical question: How does FOLFIRINOX compare to gemcitabine as first-line treatment of metastatic pancreatic cancer?

Background: Single-agent gemcitabine is the standard first-line treatment for metastatic pancreatic cancer. Preclinical studies followed by Phase 1 and Phase 2 studies have demonstrated response to the oxaliplatin, irinotecan, leucovorin, and fluorouracil regimen (FOLFIRINOX).

Study design: Multicenter, randomized, controlled Phase 2-3 trial.

Setting: Fifteen centers in France during Phase 2, which then expanded to 48 centers for Phase 3.

Synopsis: Three hundred forty-two patients with good performance status (ECOG 0 or 1) and age <76 were randomized to receive FOLFIRINOX or gemcitabine. Median survival in the FOLFIRINOX group was significantly increased, at 11.1 months, compared with 6.8 months in the gemcitabine group (HR 0.57, CI 95%, 0.45-0.73, P<000.1).

Median progression-free survival, objective response rate, and quality of life score at six months were significantly increased in the FOLFIRINOX group. Significantly more grade 3 or grade 4 toxicity was reported in the FOLFIRINOX group.

Patients with elevated bilirubin were excluded due to increased risk of irinotecan-induced toxicity, resulting in only 38% of study patients with carcinoma of the pancreatic head and low proportion of enrolled patients (14.3%) with biliary stents.

Bottom line: FOLFIRONOX was associated with a significant survival advantage compared with single-agent gemcitabine in carefully selected patients with advanced pancreatic cancer, although it was associated with increased toxicity.

Citation: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.

MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections

Clinical question: Can nationwide implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, influence healthcare-associated MRSA infection rates?

Background: MRSA is a common cause of nosocomial infection. A pilot project at a single Veterans Affairs (VA) hospital utilized a “MRSA bundle” developed from published guidelines, which resulted in decreased healthcare-associated MRSA infections. In October 2007, the MRSA bundle was implemented throughout VA hospitals nationwide.

Study design: Quality-improvement (QI) observational initiative.

Setting: One hundred fifty-eight acute-care VA hospitals in the U.S.

Synopsis: From October 2007 to June 2010, there were 1,934,598 admissions, transfers, or discharges, and 8,318,675 patient-days. Of this study group, 96% of patients were screened at admission and 93% were screened at transfer or discharge. MRSA colonization or infection at the time of admission was 13.6%. Rates of healthcare-associated MRSA infection declined 45% in the non-ICU setting (0.47 to 0.26 per 1,000 patient-days, P<0.001) and 62% in the ICU setting (1.64 to 0.62 per 1,000 patient days, P<0.001).

It is unclear how much each individual component of the MRSA bundle impacted the declining MRSA infection rate.

Bottom line: Implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, decreased the healthcare-associated MRSA infection rate in a large hospital system.

Citation: Jain R, Kralovi S, Evans M, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-1430.

New Left Bundle Branch Block Does Not Predict MI

Clinical question: How does the chronicity of left bundle branch block (LBBB) impact diagnosis and outcome in patients undergoing evaluation for acute myocardial infarction (MI)?

Background: ACA/AHA guidelines recommend that patients with new or presumed new LBBB undergo early reperfusion therapy. However, previous studies have shown that a minority of patients with new LBBB are diagnosed with MI.

Study design: Prospective cohort study.

Setting: University hospital in the U.S.

Synopsis: From 1994 to 2009, 401 consecutive patients undergoing evaluation for acute coronary syndrome with LBBB on initial ECG were included in the analysis. Of these patients, 64% had new (37%) or presumably new (27%) LBBB. Twenty-nine percent were diagnosed with MI, but there was no difference in frequency or size of MI between the new, presumably new, or chronic LBBB groups.

Concordant ST-T changes were an independent predictor of MI (OR 17, 95% CI 3.4-81, P<0.001) and mortality (OR 4.3, 95% CI 1.3-15, P<0.001), although this finding was present in only about 11% of the patient group.

Bottom line: Left bundle branch block is not a predictor of MI, although concordant ST-T changes were an independent predictor of MI and mortality.

Citation: Kontos MC, Aziz HA, Chau VQ, et al. Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction. Am Heart J. 2011;161(4):698-704.

Acute Beta-Blocker Therapy for MI Increased Risk of Shock

Clinical question: How does acute beta-blocker therapy in myocardial infarction (MI) impact outcome?

Background: Long-term treatment with beta-blockers after myocardial infarction (MI) reduces mortality. However, data regarding outcome after acute use of beta-blockers in the first 24 hours of MI is conflicting. Updated ACA/AHA guidelines for STEMI and NSTEMI recommend caution when using beta-blockers in the first 24 hours, particularly in patients at risk for shock.

Study design: Observational registry study.

Setting: Two hundred ninety-one U.S hospitals.

Synopsis: More than 34,600 patients diagnosed with STEMI and NSTEMI from January 2007 to June 2008 were identified from a national QI MI registry. Patients were stratified by guideline-stated risk factors for shock; age >70, HR >110, and systolic BP <120 were associated with increased risk of composite outcome of shock or death.

At least one high-risk factor was present in 63% of the NSTEMI patients and 45% of STEMI patients; however, >90% of these patients received acute beta-blocker therapy. Nearly half (49%) of the NSTEMI patients received beta-blockers in the ED and 62% of the STEMI patients received beta-blockers before PCI.

In a multivariable model, NSTEMI patients receiving beta-blocker therapy in the ED were more likely to develop cardiogenic shock (OR 1.54, 95% CI 1.26-1.88, P<.001), as were STEMI patients receiving beta-blocker therapy prior to PCI (1.40, 95% CI 1.10-1.79, P=.006).

Bottom line: Caution should be exercised when using beta-blocker therapy during acute MI, particularly in the ED or prior to primary PCI.

Citation: Kontos MC, Diercks DB, Ho MP, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology’s NCDR. Am Heart J. 2011;161(5):864-870.

Clinical question: Is transcatheter aortic-valve replacement comparable to surgical valve replacement in high-operative-risk patients?

Background: In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, patients who were not surgical candidates underwent transcatheter aortic-valve replacement, resulting in reduced symptoms and 20% improvement in one-year survival rates. Transcatheter valve replacement has not been compared to surgical replacement in high-operative-risk patients who remain candidates for surgical replacement.

Study design: Randomized controlled trial powered for noninferiority.

Setting: Twenty-five centers in the U.S., Canada, and Germany.

Synopsis: Six-hundred ninety-nine high-operative-risk patients with severe aortic stenosis were randomized to undergo transcatheter aortic-valve replacement or surgical replacement. In the intention-to-treat analysis, all-cause mortality rates were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% vs. 26.8% at one year (P=0.44). Rates of major stroke were 3.8% in the transcatheter group compared with 2.1% in the surgical group at 30 days (P=0.20) and 5.1% vs. 2.4% at one year (P=0.07).

The transcatheter group had a significantly higher rate of major vascular complications, but had lower rates of major bleeding and new onset-atrial fibrillation. At one year, improvement in cardiac symptoms and the six-minute-walk distance were not significantly different in the two groups.

Bottom line: In high-operative-risk patients with severe aortic stenosis, transcatheter and surgical aortic-valve replacement had similar mortality at 30 days and one year, but there were a few significant differences in periprocedural risks.

Citation: Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.

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

Clinical question: Is transcatheter aortic-valve replacement comparable to surgical valve replacement in high-operative-risk patients?

Background: In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, patients who were not surgical candidates underwent transcatheter aortic-valve replacement, resulting in reduced symptoms and 20% improvement in one-year survival rates. Transcatheter valve replacement has not been compared to surgical replacement in high-operative-risk patients who remain candidates for surgical replacement.

Study design: Randomized controlled trial powered for noninferiority.

Setting: Twenty-five centers in the U.S., Canada, and Germany.

Synopsis: Six-hundred ninety-nine high-operative-risk patients with severe aortic stenosis were randomized to undergo transcatheter aortic-valve replacement or surgical replacement. In the intention-to-treat analysis, all-cause mortality rates were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% vs. 26.8% at one year (P=0.44). Rates of major stroke were 3.8% in the transcatheter group compared with 2.1% in the surgical group at 30 days (P=0.20) and 5.1% vs. 2.4% at one year (P=0.07).

The transcatheter group had a significantly higher rate of major vascular complications, but had lower rates of major bleeding and new onset-atrial fibrillation. At one year, improvement in cardiac symptoms and the six-minute-walk distance were not significantly different in the two groups.

Bottom line: In high-operative-risk patients with severe aortic stenosis, transcatheter and surgical aortic-valve replacement had similar mortality at 30 days and one year, but there were a few significant differences in periprocedural risks.

Citation: Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.

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Clinical question: Is transcatheter aortic-valve replacement comparable to surgical valve replacement in high-operative-risk patients?

Background: In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, patients who were not surgical candidates underwent transcatheter aortic-valve replacement, resulting in reduced symptoms and 20% improvement in one-year survival rates. Transcatheter valve replacement has not been compared to surgical replacement in high-operative-risk patients who remain candidates for surgical replacement.

Study design: Randomized controlled trial powered for noninferiority.

Setting: Twenty-five centers in the U.S., Canada, and Germany.

Synopsis: Six-hundred ninety-nine high-operative-risk patients with severe aortic stenosis were randomized to undergo transcatheter aortic-valve replacement or surgical replacement. In the intention-to-treat analysis, all-cause mortality rates were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% vs. 26.8% at one year (P=0.44). Rates of major stroke were 3.8% in the transcatheter group compared with 2.1% in the surgical group at 30 days (P=0.20) and 5.1% vs. 2.4% at one year (P=0.07).

The transcatheter group had a significantly higher rate of major vascular complications, but had lower rates of major bleeding and new onset-atrial fibrillation. At one year, improvement in cardiac symptoms and the six-minute-walk distance were not significantly different in the two groups.

Bottom line: In high-operative-risk patients with severe aortic stenosis, transcatheter and surgical aortic-valve replacement had similar mortality at 30 days and one year, but there were a few significant differences in periprocedural risks.

Citation: Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.

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