Alexander R. Carbo, MD, SFHM

Clinical question: With the current use of warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation, what do the most recent data show with regard to time spent in the therapeutic window, stroke risk, and bleeding risk?

Background: Historically, warfarin has been shown to decrease stroke risk in nonvalvular atrial fibrillation by 62% compared with placebo, balanced by a significant risk of bleeding. Despite the availability of multiple new antithrombotic agents, warfarin will likely continue to be widely used given its lower cost. As a result, physicians need an accurate estimate of warfarin’s efficacy and safety as currently used in practice.

Study design: Meta-analysis of randomized controlled trials (RCTs).

Setting: RCTs comparing warfarin to an alternative antithrombotic agent from 2001 to 2011.

Synopsis: Eight RCTs of nonvalvular atrial fibrillation were included, yielding data on 32,053 patients with a mean age range of 70 to 82 years and widely variable CHADS2 scores. The time spent at a therapeutic INR was found to be improved when compared to historical rates, ranging from 55% to 68%. The rate of stroke or non-central-nervous-system embolism ranged from 1.2% to 2.3% per year, with a pooled event rate of 1.66% per year, compared with 2.09% per year in earlier trials.

Major bleeding was defined differently across studies, with a reported incidence of 1.4% to 3.4% per year, a pooled event rate of intracranial hemorrhage of 0.61%, and a cumulative adverse event rate of 3.0% to 7.64%. Stroke rates were highest in patients older than 75 years, women, those with a history of transient ischemic attack or stroke, those new to warfarin, and those with higher CHADS2 scores.

Bottom line: Warfarin as currently used is associated with an annual rate of stroke or systemic embolism of 1.66% and an annual rate of major bleeding ranging from 1.4% to 3.4%.

Citation: Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172:623-631.

Clinical question: With the current use of warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation, what do the most recent data show with regard to time spent in the therapeutic window, stroke risk, and bleeding risk?

Background: Historically, warfarin has been shown to decrease stroke risk in nonvalvular atrial fibrillation by 62% compared with placebo, balanced by a significant risk of bleeding. Despite the availability of multiple new antithrombotic agents, warfarin will likely continue to be widely used given its lower cost. As a result, physicians need an accurate estimate of warfarin’s efficacy and safety as currently used in practice.

Study design: Meta-analysis of randomized controlled trials (RCTs).

Setting: RCTs comparing warfarin to an alternative antithrombotic agent from 2001 to 2011.

Synopsis: Eight RCTs of nonvalvular atrial fibrillation were included, yielding data on 32,053 patients with a mean age range of 70 to 82 years and widely variable CHADS2 scores. The time spent at a therapeutic INR was found to be improved when compared to historical rates, ranging from 55% to 68%. The rate of stroke or non-central-nervous-system embolism ranged from 1.2% to 2.3% per year, with a pooled event rate of 1.66% per year, compared with 2.09% per year in earlier trials.

Major bleeding was defined differently across studies, with a reported incidence of 1.4% to 3.4% per year, a pooled event rate of intracranial hemorrhage of 0.61%, and a cumulative adverse event rate of 3.0% to 7.64%. Stroke rates were highest in patients older than 75 years, women, those with a history of transient ischemic attack or stroke, those new to warfarin, and those with higher CHADS2 scores.

Bottom line: Warfarin as currently used is associated with an annual rate of stroke or systemic embolism of 1.66% and an annual rate of major bleeding ranging from 1.4% to 3.4%.

Citation: Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172:623-631.

Clinical question: With the current use of warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation, what do the most recent data show with regard to time spent in the therapeutic window, stroke risk, and bleeding risk?

Background: Historically, warfarin has been shown to decrease stroke risk in nonvalvular atrial fibrillation by 62% compared with placebo, balanced by a significant risk of bleeding. Despite the availability of multiple new antithrombotic agents, warfarin will likely continue to be widely used given its lower cost. As a result, physicians need an accurate estimate of warfarin’s efficacy and safety as currently used in practice.

Study design: Meta-analysis of randomized controlled trials (RCTs).

Setting: RCTs comparing warfarin to an alternative antithrombotic agent from 2001 to 2011.

Synopsis: Eight RCTs of nonvalvular atrial fibrillation were included, yielding data on 32,053 patients with a mean age range of 70 to 82 years and widely variable CHADS2 scores. The time spent at a therapeutic INR was found to be improved when compared to historical rates, ranging from 55% to 68%. The rate of stroke or non-central-nervous-system embolism ranged from 1.2% to 2.3% per year, with a pooled event rate of 1.66% per year, compared with 2.09% per year in earlier trials.

Major bleeding was defined differently across studies, with a reported incidence of 1.4% to 3.4% per year, a pooled event rate of intracranial hemorrhage of 0.61%, and a cumulative adverse event rate of 3.0% to 7.64%. Stroke rates were highest in patients older than 75 years, women, those with a history of transient ischemic attack or stroke, those new to warfarin, and those with higher CHADS2 scores.

Bottom line: Warfarin as currently used is associated with an annual rate of stroke or systemic embolism of 1.66% and an annual rate of major bleeding ranging from 1.4% to 3.4%.

Citation: Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172:623-631.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. High-dose vs. low-dose clopidogrel after cardiac stenting
2. Rates of overdiagnosis of PE with CTPA
3. Outcomes of hospitalists with PAs or residents
4. White coats and MRSA
5. Correlation of vital signs and pain
6. Rate of asymptomatic perioperative MI
7. Relationship of opioid prescription patterns and overdose
8. Interdisciplinary rounds and rates of adverse events

High-Dose Clopidogrel Is Not Superior to Standard-Dose Clopidogrel in Patients with High On-Treatment Platelet Activity after Percutaneous Corona

Clinical question: In patients with high on-treatment platelet activity, does the use of high-dose clopidogrel after percutaneous coronary intervention (PCI) decrease the risk of cardiovascular events?

Background: In patients receiving clopidogrel, high platelet reactivity after PCI is associated with an increase in cardiovascular events. At present, treatments targeted at this population are not well-defined.

Study design: Randomized, double-blind, active-control trial.

Setting: Eighty-three centers in North America.

Synopsis: Researchers randomized 2,214 patients with drug-eluting stents to receive either high-dose clopidogrel (600 mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily). At six months, the primary endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis was no different in the two groups (2.3% in the high-dose group versus 2.3% in the standard-dose group; hazard ratio 1.01).

Bottom line: High-dose clopidogrel adds no benefit over standard-dose clopidogrel in patients with high platelet reactivity who have undergone PCI with drug-eluting stent placement.

Citation: Price MJ, Berger PB, Teirstein PS, et al. Standard- vs. high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097-1105.

Computed Tomographic Pulmonary Angiography (CTPA) Is Associated with Overdiagnosis and Overtreatment of Pulmonary Embolism (PE)

Clinical question: Is the use of CTPA associated with increased incidence of PE and increased complications from anticoagulation treatment?

Background: CTPA is a sensitive, noninvasive test for diagnosing PE that could have a drawback: identifying potentially clinically unimportant (small) pulmonary emboli that subsequently are treated. Overtreatment might be associated with patient harm due to increased complications of anticoagulation therapy.

Study design: Time-trend analysis of PE between the pre-CTPA period (1993 to 1998) and the post-CTPA period (1998 to 2006).

Setting: Nongovernmental U.S. hospitals.

Synopsis: The Nationwide Inpatient Sample and Multiple Cause-of-Death databases were used to determine national estimates of hospitalization for PE, along with morbidity and mortality from PE.

The age-adjusted analysis revealed a statistically significant increase in the incidence of PE diagnosis after introduction of CTPA (to 112 per 100,000 from 62 per 100,000), with minimal change in overall PE mortality. This was accompanied by a substantial reduction in PE case-fatality rate, the rate of hospital deaths among patients with a diagnosis of pulmonary embolism.

Availability of CTPA was associated with a significant increase in anticoagulation complication rates (to 5.3 per 100,000 from 3.1 per 100,000), including statistically significant increases in gastrointestinal hemorrhage and secondary thrombocytopenia, and a trend toward higher rates of intracranial hemorrhage.

Bottom line: Introduction of CTPA was associated with changes suggestive of overdiagnosis (increased incidence, relatively unchanged mortality) and overtreatment (increased complication rates) of PE, but it remains unknown which small PEs are clinically significant.

Citation: Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.

Hospitalist-Physician Assistant Teams Associated with Longer Length of Stay, No Change in Mortality, Readmission Rates

Clinical question: Do length of stay (LOS), hospital mortality, or readmission rate change if hospitalists and physician assistants, or the traditional resident-hospitalist teams, provide the patient care?

Background: Resident work-hour limitations require new models of care for hospitalized patients. Many academic medical centers have hired physician assistants to work with hospitalists to provide care. Little is known about how these models affect such outcomes as LOS, inpatient mortality rates, and readmission rates.

Study design: Retrospective cohort.

Setting: A 430-bed urban academic medical center in Milwaukee.

Synopsis: Administrative data were gathered on 9,681 patients admitted to the general medical service. Of those enrolled, 2,171 were cared for by a hospitalist-physician assistant (H-PA) team, while resident-hospitalist teams cared for 7,510 patients. Patient assignment was dependent on time of admission but not on patient complexity. Patients admitted overnight after the resident team capped were assigned to the H-PA team the next morning, resulting in increased transitions of care for the H-PA team.

Adjusted analyses revealed a 6.45% increase in LOS for the H-PA team compared with the resident team. Charges, inpatient mortality, and readmission rates at seven, 14, and 30 days were unchanged. Subgroup analyses revealed smaller differences in LOS for H-PA teams and resident-hospitalist teams with the same hospitalist (LOS 5.44% higher, P=0.081).

Conclusions from this study are limited due to lack of randomization of assignment, the retrospective design, and the use of administrative data at one institution.

Bottom line: Hospitalist-PA teams might result in a slightly increased LOS compared with the traditional resident teams; however, inpatient mortality and readmission rates are similar.

Citation: Singh S, Fletcher KE, Schapira MM, et al. A comparison of outcomes of general medical inpatient care provided by a hospitalist-physician assistant model vs a traditional resident-based model. J Hosp Med. 2011;6:122-130.

Washing White Coats Does Not Lower MRSA Bacterial Contamination

Clinical question: Are clean, short-sleeved uniforms less likely to carry MRSA than regularly laundered long-sleeved white coats?

Background: Studies have shown that bacteria frequently colonize in physician garments. However, evidence that short-sleeved garments or newly laundered garments are less likely to be contaminated has been lacking. Despite the paucity of evidence, the British Department of Health barred the use of traditional white coats and long-sleeved garments in 2007.

Study design: Prospective, randomized, controlled trial.

Setting: Urban U.S. hospital.

Synopsis: Study authors randomized 100 internal-medicine residents and hospitalists to their own long-sleeved white coats or freshly laundered short-sleeved uniforms from August 2008 to November 2009. Swabs were taken from the sleeves of the white coats or uniform, the breast pocket, and the volar wrist surface of the dominant hand. Swabs were cultured for MRSA and for general colony count.

Results showed no significant difference in colony counts or MRSA colonization in any of the sites tested between the newly laundered uniforms and the white coats. Additionally, there was no effect in relation to the frequency of laundering the white coats. Notably, within three hours of donning freshly laundered uniforms, bacterial counts approached 50% of the total bacterial counts seen at eight hours.

Bottom line: Laundering of uniforms does not affect MRSA colonization rate or general bacterial burden on physician uniforms or skin surfaces, though the effect on nosocomial infection has not been established.

Citation: Burden M, Cervantes L, Weed D, Keniston A, Price CS, Albert RK. Newly cleaned physician uniforms and infrequently washed white coats have similar rates of bacterial contamination after an 8-hour workday: a randomized controlled trial. J Hosp Med. 2011;6:177-182.

Self-Reported Pain Severity Does Not Correlate with Heart Rate or Blood Pressure Measurements in Pre-Hospital Setting

Clinical question: Do measured vital signs, including heart rate, blood pressure, and respiratory rate, correlate with the degree of self-reported pain?

Background: Because pain often can be associated with alterations in autonomic tone, it has been hypothesized that alterations in vital signs will occur in patients who report pain.

Study design: Retrospective cohort study.

Setting: Pre-hospital in Melbourne, Australia.

Synopsis: The authors reviewed all ambulance patient care records for patients age >14 years with a Glasgow Coma Score (GCS) >12 transported to a hospital during a seven-day period in 2005. Patients were selected for analysis if their patient care record included an initial assessment of pain severity, as measured by a numeric rating scale (NRS), in which patients rate their pain from 0 to 10.

More than half of the 3,357 patients transported by paramedics during the period were included in this analysis (n=1286). There was no correlation between heart rate or systolic blood pressure with the degree of self-reported pain. Although an increased respiratory rate was statistically correlated with a higher rating of pain, this relationship was not clinically significant, as each one-point increase in the pain rating scale was associated with a 0.16-breaths-per-minute increase in the respiratory rate.

Limitations included the large number of records excluded from analysis because pain was not evaluated, as well as numerous unmeasured confounders, including active disease processes such as sepsis, that were not accounted for.

Bottom line: Severity of pain did not correlate with heart rate or systolic blood pressure in the pre-hospital setting.

Citation: Lord B, Woollard M. The reliability of vital signs in estimating pain severity among adult patients treated by paramedics. Emerg Med J. 2011;28:147-150.

Asymptomatic Perioperative Myocardial Infarction Is Common in Patients Undergoing Noncardiac Surgery

Clinical question: In patients undergoing noncardiac surgery, what is the incidence and clinical characteristics of perioperative myocardial infarction (MI)?

Background: Though millions of patients experience perioperative MI after noncardiac surgery, little is known about the characteristics and outcomes of these patients.

Study design: Cohort study.

Setting: One hundred ninety centers in 23 countries.

Synopsis: Using data from the 8,351 patients in the POISE (PeriOperative ISchemic Evaluation) trial, this study showed that perioperative MI occurred in 5% of patients; 65% were asymptomatic. Patients who experienced postoperative MI were older and had more cardiovascular risk factors when compared to those who did not. The 30-day mortality was higher in patients with a perioperative MI (11.6%) compared with those who did not (2.2%); the presence or absence of ischemic symptoms was not associated with mortality rate.

Of the 8.3% of patients who experienced an elevation in cardiac biomarkers but who did not meet the definition of MI, there was an increased risk of nonfatal cardiac arrest and nonacute coronary revascularization. Those in the highest quartile also had increased 30-day mortality.

Bottom line: Given the high proportion of asymptomatic MIs and isolated elevations in cardiac biomarkers and the association between these events and increased risk of death, hospitalists should consider routine monitoring of troponin in at-risk patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154(8):523-528.

Patients Prescribed Higher Opioid Doses Are at Increased Risk of Opioid Overdose Death

Clinical question: What is the association between opioid prescribing patterns and fatal opioid overdose?

Background: In the past 10 years, the rate of fatal overdose from opioid prescription for pain has more than doubled. Little is known about how the indications (substance abuse disorders, cancer-related pain, chronic pain, acute pain), maximal daily dose, and scheduling (standing, as-needed, or both) of opioid prescriptions relate to this increased risk.

Study design: Case-cohort study.

Setting: Veterans Health Administration (VHA) patients.

Synopsis: The VHA’s National Patient Care Database was used to randomly select a cohort of 154,684 nonhospice/nonpalliative-care patients who were prescribed opioids from 2004 to 2008. They were compared with 750 patients who were treated with prescription opioids who died from opioid overdose during this time.

Fatal opioid overdose was a rare event (0.04%), but risk increased with higher prescribed maximum daily morphine dose-equivalence, especially when greater than or equal to 50 mg/day in all subgroups (substance abuse, acute and chronic pain, and cancer). Fatal overdoses were higher in middle-aged white men with acute or chronic pain, substance abuse disorders, and other psychiatric illness. Patients with cancer were at increased risk of fatal overdose if they were prescribed as-needed opioids alone.

Treatment with both as-needed and standing opioids did not statistically affect risk of overdose death in any subgroup.

Bottom line: Although rare, risk of fatal opioid overdose in patients prescribed opiate medication increases with higher maximum prescribed daily dose.

Citation: Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-1321.

Structured Interdisciplinary Rounds on Medical Teaching Unit Significantly Decrease Adverse Events

Clinical question: Do structured interdisciplinary rounds have an impact on the rate of adverse events?

Background: Many preventable adverse events occurring during hospitalization can be attributed to communication failures. Structured interdisciplinary rounds provide a format as well as a forum for team members to discuss patient care. Prior studies demonstrated improvements in collaboration; whether this translates to better patient care is not known.

Study design: Retrospective cohort using historic and concurrent control.

Setting: Tertiary-care teaching hospital in Chicago.

Synopsis: Structured interdisciplinary rounds, led by a nurse manager and medical director, and including nurses, residents, pharmacists, social workers, and case managers, were implemented on a medical teaching unit. New patients were discussed using a structured communication tool; existing patients were discussed in an unstructured format. Medical records were abstracted for 370 patients hospitalized after implementation of the intervention, equally divided between intervention and control units. One hundred eighty-five patients hospitalized on the intervention unit prior to the implementation of rounds served as a historic control.

Patients in the intervention unit had significantly lower rates of total adverse events (3.9 per 100 patient days in the intervention, compared with 7.2 and 7.7 per 100 patient days for the concurrent and historic control units, respectively), and preventable adverse events (0.9 per 100 patient days, compared with 2.8 and 2.1 per 100 patient days for the concurrent and historic controls, respectively).

Limitations of the study include lack of blinding of the medical record, slightly different patient populations in intervention and control groups, and the one-hospital setting, which could limit generalizability.

Bottom line: Structured interdisciplinary rounds might serve to improve communication between nurses, pharmacists, and physicians, resulting in decreases in adverse events.

Citation: O’Leary KJ, Buck R, Fligiel HM, et al. Structured interdisciplinary rounds in a medical teaching unit: improving patient safety. Arch Intern Med. 2011;171(7):678-684.

Pediatric HM Literature

Short-Course Antibiotic Therapy Effective for Bacterial Meningitis

Clinical question: Is five days of parenteral ceftriaxone as effective as 10 days for the treatment of bacterial meningitis in children?

Background: Morbidity and mortality in bacterial meningitis remain high, particularly in developing countries. Antibiotics are effective treatment, yet the optimal duration of treatment remains uncertain. Some data support a shorter duration of treatment (three to five days).

Study design: Multicountry, double-blind, placebo-controlled, randomized equivalence study.

Setting: Ten pediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam.

Synopsis: Children aged two months to 12 years with bacterial meningitis (due to Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis, or culture-negative with indicative cerebrospinal fluid findings) and without complicating medical conditions were enrolled at participating centers. All children received 80 mg/kg to 100 mg/kg of parenteral ceftriaxone daily and a repeat lumbar puncture 48 to 72 hours after initiation of therapy.

Ultimately, 1,004 children without resistant organisms, persistently positive cultures, or suppurative complications were randomized on day five of therapy to placebo or continuance of ceftriaxone for five more days.

No bacteriologic failures (primary endpoint) were evident with either five or 10 days of treatment.

In addition, no statistically significant differences were found between the groups with respect to clinical treatment failure, hearing loss, neurological sequelae, or death. Secondary analysis by organism revealed similar results.

The primary limitation of this study is that it occurred in developing countries with a fair incidence of H. influenzae meningitis and a low rate of third-generation cephalosporin resistance.

However, pneumococcal and meningococcal disease remained prominent, and this study suggests that clinically stable patients might be treated with a shorter course of parenteral ceftriaxone therapy than currently is recommended.

Bottom line: Five days of ceftriaxone is as effective as 10 days for uncomplicated bacterial meningitis in children.

Citation: Molyneux E, Nizami SQ, Saha S, et al. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Lancet. 2011;377:1837-1845.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. High-dose vs. low-dose clopidogrel after cardiac stenting
2. Rates of overdiagnosis of PE with CTPA
3. Outcomes of hospitalists with PAs or residents
4. White coats and MRSA
5. Correlation of vital signs and pain
6. Rate of asymptomatic perioperative MI
7. Relationship of opioid prescription patterns and overdose
8. Interdisciplinary rounds and rates of adverse events

High-Dose Clopidogrel Is Not Superior to Standard-Dose Clopidogrel in Patients with High On-Treatment Platelet Activity after Percutaneous Corona

Clinical question: In patients with high on-treatment platelet activity, does the use of high-dose clopidogrel after percutaneous coronary intervention (PCI) decrease the risk of cardiovascular events?

Background: In patients receiving clopidogrel, high platelet reactivity after PCI is associated with an increase in cardiovascular events. At present, treatments targeted at this population are not well-defined.

Study design: Randomized, double-blind, active-control trial.

Setting: Eighty-three centers in North America.

Synopsis: Researchers randomized 2,214 patients with drug-eluting stents to receive either high-dose clopidogrel (600 mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily). At six months, the primary endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis was no different in the two groups (2.3% in the high-dose group versus 2.3% in the standard-dose group; hazard ratio 1.01).

Bottom line: High-dose clopidogrel adds no benefit over standard-dose clopidogrel in patients with high platelet reactivity who have undergone PCI with drug-eluting stent placement.

Citation: Price MJ, Berger PB, Teirstein PS, et al. Standard- vs. high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097-1105.

Computed Tomographic Pulmonary Angiography (CTPA) Is Associated with Overdiagnosis and Overtreatment of Pulmonary Embolism (PE)

Clinical question: Is the use of CTPA associated with increased incidence of PE and increased complications from anticoagulation treatment?

Background: CTPA is a sensitive, noninvasive test for diagnosing PE that could have a drawback: identifying potentially clinically unimportant (small) pulmonary emboli that subsequently are treated. Overtreatment might be associated with patient harm due to increased complications of anticoagulation therapy.

Study design: Time-trend analysis of PE between the pre-CTPA period (1993 to 1998) and the post-CTPA period (1998 to 2006).

Setting: Nongovernmental U.S. hospitals.

Synopsis: The Nationwide Inpatient Sample and Multiple Cause-of-Death databases were used to determine national estimates of hospitalization for PE, along with morbidity and mortality from PE.

The age-adjusted analysis revealed a statistically significant increase in the incidence of PE diagnosis after introduction of CTPA (to 112 per 100,000 from 62 per 100,000), with minimal change in overall PE mortality. This was accompanied by a substantial reduction in PE case-fatality rate, the rate of hospital deaths among patients with a diagnosis of pulmonary embolism.

Availability of CTPA was associated with a significant increase in anticoagulation complication rates (to 5.3 per 100,000 from 3.1 per 100,000), including statistically significant increases in gastrointestinal hemorrhage and secondary thrombocytopenia, and a trend toward higher rates of intracranial hemorrhage.

Bottom line: Introduction of CTPA was associated with changes suggestive of overdiagnosis (increased incidence, relatively unchanged mortality) and overtreatment (increased complication rates) of PE, but it remains unknown which small PEs are clinically significant.

Citation: Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.

Hospitalist-Physician Assistant Teams Associated with Longer Length of Stay, No Change in Mortality, Readmission Rates

Clinical question: Do length of stay (LOS), hospital mortality, or readmission rate change if hospitalists and physician assistants, or the traditional resident-hospitalist teams, provide the patient care?

Background: Resident work-hour limitations require new models of care for hospitalized patients. Many academic medical centers have hired physician assistants to work with hospitalists to provide care. Little is known about how these models affect such outcomes as LOS, inpatient mortality rates, and readmission rates.

Study design: Retrospective cohort.

Setting: A 430-bed urban academic medical center in Milwaukee.

Synopsis: Administrative data were gathered on 9,681 patients admitted to the general medical service. Of those enrolled, 2,171 were cared for by a hospitalist-physician assistant (H-PA) team, while resident-hospitalist teams cared for 7,510 patients. Patient assignment was dependent on time of admission but not on patient complexity. Patients admitted overnight after the resident team capped were assigned to the H-PA team the next morning, resulting in increased transitions of care for the H-PA team.

Adjusted analyses revealed a 6.45% increase in LOS for the H-PA team compared with the resident team. Charges, inpatient mortality, and readmission rates at seven, 14, and 30 days were unchanged. Subgroup analyses revealed smaller differences in LOS for H-PA teams and resident-hospitalist teams with the same hospitalist (LOS 5.44% higher, P=0.081).

Conclusions from this study are limited due to lack of randomization of assignment, the retrospective design, and the use of administrative data at one institution.

Bottom line: Hospitalist-PA teams might result in a slightly increased LOS compared with the traditional resident teams; however, inpatient mortality and readmission rates are similar.

Citation: Singh S, Fletcher KE, Schapira MM, et al. A comparison of outcomes of general medical inpatient care provided by a hospitalist-physician assistant model vs a traditional resident-based model. J Hosp Med. 2011;6:122-130.

Washing White Coats Does Not Lower MRSA Bacterial Contamination

Clinical question: Are clean, short-sleeved uniforms less likely to carry MRSA than regularly laundered long-sleeved white coats?

Background: Studies have shown that bacteria frequently colonize in physician garments. However, evidence that short-sleeved garments or newly laundered garments are less likely to be contaminated has been lacking. Despite the paucity of evidence, the British Department of Health barred the use of traditional white coats and long-sleeved garments in 2007.

Study design: Prospective, randomized, controlled trial.

Setting: Urban U.S. hospital.

Synopsis: Study authors randomized 100 internal-medicine residents and hospitalists to their own long-sleeved white coats or freshly laundered short-sleeved uniforms from August 2008 to November 2009. Swabs were taken from the sleeves of the white coats or uniform, the breast pocket, and the volar wrist surface of the dominant hand. Swabs were cultured for MRSA and for general colony count.

Results showed no significant difference in colony counts or MRSA colonization in any of the sites tested between the newly laundered uniforms and the white coats. Additionally, there was no effect in relation to the frequency of laundering the white coats. Notably, within three hours of donning freshly laundered uniforms, bacterial counts approached 50% of the total bacterial counts seen at eight hours.

Bottom line: Laundering of uniforms does not affect MRSA colonization rate or general bacterial burden on physician uniforms or skin surfaces, though the effect on nosocomial infection has not been established.

Citation: Burden M, Cervantes L, Weed D, Keniston A, Price CS, Albert RK. Newly cleaned physician uniforms and infrequently washed white coats have similar rates of bacterial contamination after an 8-hour workday: a randomized controlled trial. J Hosp Med. 2011;6:177-182.

Self-Reported Pain Severity Does Not Correlate with Heart Rate or Blood Pressure Measurements in Pre-Hospital Setting

Clinical question: Do measured vital signs, including heart rate, blood pressure, and respiratory rate, correlate with the degree of self-reported pain?

Background: Because pain often can be associated with alterations in autonomic tone, it has been hypothesized that alterations in vital signs will occur in patients who report pain.

Study design: Retrospective cohort study.

Setting: Pre-hospital in Melbourne, Australia.

Synopsis: The authors reviewed all ambulance patient care records for patients age >14 years with a Glasgow Coma Score (GCS) >12 transported to a hospital during a seven-day period in 2005. Patients were selected for analysis if their patient care record included an initial assessment of pain severity, as measured by a numeric rating scale (NRS), in which patients rate their pain from 0 to 10.

More than half of the 3,357 patients transported by paramedics during the period were included in this analysis (n=1286). There was no correlation between heart rate or systolic blood pressure with the degree of self-reported pain. Although an increased respiratory rate was statistically correlated with a higher rating of pain, this relationship was not clinically significant, as each one-point increase in the pain rating scale was associated with a 0.16-breaths-per-minute increase in the respiratory rate.

Limitations included the large number of records excluded from analysis because pain was not evaluated, as well as numerous unmeasured confounders, including active disease processes such as sepsis, that were not accounted for.

Bottom line: Severity of pain did not correlate with heart rate or systolic blood pressure in the pre-hospital setting.

Citation: Lord B, Woollard M. The reliability of vital signs in estimating pain severity among adult patients treated by paramedics. Emerg Med J. 2011;28:147-150.

Asymptomatic Perioperative Myocardial Infarction Is Common in Patients Undergoing Noncardiac Surgery

Clinical question: In patients undergoing noncardiac surgery, what is the incidence and clinical characteristics of perioperative myocardial infarction (MI)?

Background: Though millions of patients experience perioperative MI after noncardiac surgery, little is known about the characteristics and outcomes of these patients.

Study design: Cohort study.

Setting: One hundred ninety centers in 23 countries.

Synopsis: Using data from the 8,351 patients in the POISE (PeriOperative ISchemic Evaluation) trial, this study showed that perioperative MI occurred in 5% of patients; 65% were asymptomatic. Patients who experienced postoperative MI were older and had more cardiovascular risk factors when compared to those who did not. The 30-day mortality was higher in patients with a perioperative MI (11.6%) compared with those who did not (2.2%); the presence or absence of ischemic symptoms was not associated with mortality rate.

Of the 8.3% of patients who experienced an elevation in cardiac biomarkers but who did not meet the definition of MI, there was an increased risk of nonfatal cardiac arrest and nonacute coronary revascularization. Those in the highest quartile also had increased 30-day mortality.

Bottom line: Given the high proportion of asymptomatic MIs and isolated elevations in cardiac biomarkers and the association between these events and increased risk of death, hospitalists should consider routine monitoring of troponin in at-risk patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154(8):523-528.

Patients Prescribed Higher Opioid Doses Are at Increased Risk of Opioid Overdose Death

Clinical question: What is the association between opioid prescribing patterns and fatal opioid overdose?

Background: In the past 10 years, the rate of fatal overdose from opioid prescription for pain has more than doubled. Little is known about how the indications (substance abuse disorders, cancer-related pain, chronic pain, acute pain), maximal daily dose, and scheduling (standing, as-needed, or both) of opioid prescriptions relate to this increased risk.

Study design: Case-cohort study.

Setting: Veterans Health Administration (VHA) patients.

Synopsis: The VHA’s National Patient Care Database was used to randomly select a cohort of 154,684 nonhospice/nonpalliative-care patients who were prescribed opioids from 2004 to 2008. They were compared with 750 patients who were treated with prescription opioids who died from opioid overdose during this time.

Fatal opioid overdose was a rare event (0.04%), but risk increased with higher prescribed maximum daily morphine dose-equivalence, especially when greater than or equal to 50 mg/day in all subgroups (substance abuse, acute and chronic pain, and cancer). Fatal overdoses were higher in middle-aged white men with acute or chronic pain, substance abuse disorders, and other psychiatric illness. Patients with cancer were at increased risk of fatal overdose if they were prescribed as-needed opioids alone.

Treatment with both as-needed and standing opioids did not statistically affect risk of overdose death in any subgroup.

Bottom line: Although rare, risk of fatal opioid overdose in patients prescribed opiate medication increases with higher maximum prescribed daily dose.

Citation: Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-1321.

Structured Interdisciplinary Rounds on Medical Teaching Unit Significantly Decrease Adverse Events

Clinical question: Do structured interdisciplinary rounds have an impact on the rate of adverse events?

Background: Many preventable adverse events occurring during hospitalization can be attributed to communication failures. Structured interdisciplinary rounds provide a format as well as a forum for team members to discuss patient care. Prior studies demonstrated improvements in collaboration; whether this translates to better patient care is not known.

Study design: Retrospective cohort using historic and concurrent control.

Setting: Tertiary-care teaching hospital in Chicago.

Synopsis: Structured interdisciplinary rounds, led by a nurse manager and medical director, and including nurses, residents, pharmacists, social workers, and case managers, were implemented on a medical teaching unit. New patients were discussed using a structured communication tool; existing patients were discussed in an unstructured format. Medical records were abstracted for 370 patients hospitalized after implementation of the intervention, equally divided between intervention and control units. One hundred eighty-five patients hospitalized on the intervention unit prior to the implementation of rounds served as a historic control.

Patients in the intervention unit had significantly lower rates of total adverse events (3.9 per 100 patient days in the intervention, compared with 7.2 and 7.7 per 100 patient days for the concurrent and historic control units, respectively), and preventable adverse events (0.9 per 100 patient days, compared with 2.8 and 2.1 per 100 patient days for the concurrent and historic controls, respectively).

Limitations of the study include lack of blinding of the medical record, slightly different patient populations in intervention and control groups, and the one-hospital setting, which could limit generalizability.

Bottom line: Structured interdisciplinary rounds might serve to improve communication between nurses, pharmacists, and physicians, resulting in decreases in adverse events.

Citation: O’Leary KJ, Buck R, Fligiel HM, et al. Structured interdisciplinary rounds in a medical teaching unit: improving patient safety. Arch Intern Med. 2011;171(7):678-684.

Pediatric HM Literature

Short-Course Antibiotic Therapy Effective for Bacterial Meningitis

Clinical question: Is five days of parenteral ceftriaxone as effective as 10 days for the treatment of bacterial meningitis in children?

Background: Morbidity and mortality in bacterial meningitis remain high, particularly in developing countries. Antibiotics are effective treatment, yet the optimal duration of treatment remains uncertain. Some data support a shorter duration of treatment (three to five days).

Study design: Multicountry, double-blind, placebo-controlled, randomized equivalence study.

Setting: Ten pediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam.

Synopsis: Children aged two months to 12 years with bacterial meningitis (due to Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis, or culture-negative with indicative cerebrospinal fluid findings) and without complicating medical conditions were enrolled at participating centers. All children received 80 mg/kg to 100 mg/kg of parenteral ceftriaxone daily and a repeat lumbar puncture 48 to 72 hours after initiation of therapy.

Ultimately, 1,004 children without resistant organisms, persistently positive cultures, or suppurative complications were randomized on day five of therapy to placebo or continuance of ceftriaxone for five more days.

No bacteriologic failures (primary endpoint) were evident with either five or 10 days of treatment.

In addition, no statistically significant differences were found between the groups with respect to clinical treatment failure, hearing loss, neurological sequelae, or death. Secondary analysis by organism revealed similar results.

The primary limitation of this study is that it occurred in developing countries with a fair incidence of H. influenzae meningitis and a low rate of third-generation cephalosporin resistance.

However, pneumococcal and meningococcal disease remained prominent, and this study suggests that clinically stable patients might be treated with a shorter course of parenteral ceftriaxone therapy than currently is recommended.

Bottom line: Five days of ceftriaxone is as effective as 10 days for uncomplicated bacterial meningitis in children.

Citation: Molyneux E, Nizami SQ, Saha S, et al. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Lancet. 2011;377:1837-1845.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. High-dose vs. low-dose clopidogrel after cardiac stenting
2. Rates of overdiagnosis of PE with CTPA
3. Outcomes of hospitalists with PAs or residents
4. White coats and MRSA
5. Correlation of vital signs and pain
6. Rate of asymptomatic perioperative MI
7. Relationship of opioid prescription patterns and overdose
8. Interdisciplinary rounds and rates of adverse events

High-Dose Clopidogrel Is Not Superior to Standard-Dose Clopidogrel in Patients with High On-Treatment Platelet Activity after Percutaneous Corona

Clinical question: In patients with high on-treatment platelet activity, does the use of high-dose clopidogrel after percutaneous coronary intervention (PCI) decrease the risk of cardiovascular events?

Background: In patients receiving clopidogrel, high platelet reactivity after PCI is associated with an increase in cardiovascular events. At present, treatments targeted at this population are not well-defined.

Study design: Randomized, double-blind, active-control trial.

Setting: Eighty-three centers in North America.

Synopsis: Researchers randomized 2,214 patients with drug-eluting stents to receive either high-dose clopidogrel (600 mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily). At six months, the primary endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis was no different in the two groups (2.3% in the high-dose group versus 2.3% in the standard-dose group; hazard ratio 1.01).

Bottom line: High-dose clopidogrel adds no benefit over standard-dose clopidogrel in patients with high platelet reactivity who have undergone PCI with drug-eluting stent placement.

Citation: Price MJ, Berger PB, Teirstein PS, et al. Standard- vs. high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097-1105.

Computed Tomographic Pulmonary Angiography (CTPA) Is Associated with Overdiagnosis and Overtreatment of Pulmonary Embolism (PE)

Clinical question: Is the use of CTPA associated with increased incidence of PE and increased complications from anticoagulation treatment?

Background: CTPA is a sensitive, noninvasive test for diagnosing PE that could have a drawback: identifying potentially clinically unimportant (small) pulmonary emboli that subsequently are treated. Overtreatment might be associated with patient harm due to increased complications of anticoagulation therapy.

Study design: Time-trend analysis of PE between the pre-CTPA period (1993 to 1998) and the post-CTPA period (1998 to 2006).

Setting: Nongovernmental U.S. hospitals.

Synopsis: The Nationwide Inpatient Sample and Multiple Cause-of-Death databases were used to determine national estimates of hospitalization for PE, along with morbidity and mortality from PE.

The age-adjusted analysis revealed a statistically significant increase in the incidence of PE diagnosis after introduction of CTPA (to 112 per 100,000 from 62 per 100,000), with minimal change in overall PE mortality. This was accompanied by a substantial reduction in PE case-fatality rate, the rate of hospital deaths among patients with a diagnosis of pulmonary embolism.

Availability of CTPA was associated with a significant increase in anticoagulation complication rates (to 5.3 per 100,000 from 3.1 per 100,000), including statistically significant increases in gastrointestinal hemorrhage and secondary thrombocytopenia, and a trend toward higher rates of intracranial hemorrhage.

Bottom line: Introduction of CTPA was associated with changes suggestive of overdiagnosis (increased incidence, relatively unchanged mortality) and overtreatment (increased complication rates) of PE, but it remains unknown which small PEs are clinically significant.

Citation: Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.

Hospitalist-Physician Assistant Teams Associated with Longer Length of Stay, No Change in Mortality, Readmission Rates

Clinical question: Do length of stay (LOS), hospital mortality, or readmission rate change if hospitalists and physician assistants, or the traditional resident-hospitalist teams, provide the patient care?

Background: Resident work-hour limitations require new models of care for hospitalized patients. Many academic medical centers have hired physician assistants to work with hospitalists to provide care. Little is known about how these models affect such outcomes as LOS, inpatient mortality rates, and readmission rates.

Study design: Retrospective cohort.

Setting: A 430-bed urban academic medical center in Milwaukee.

Synopsis: Administrative data were gathered on 9,681 patients admitted to the general medical service. Of those enrolled, 2,171 were cared for by a hospitalist-physician assistant (H-PA) team, while resident-hospitalist teams cared for 7,510 patients. Patient assignment was dependent on time of admission but not on patient complexity. Patients admitted overnight after the resident team capped were assigned to the H-PA team the next morning, resulting in increased transitions of care for the H-PA team.

Adjusted analyses revealed a 6.45% increase in LOS for the H-PA team compared with the resident team. Charges, inpatient mortality, and readmission rates at seven, 14, and 30 days were unchanged. Subgroup analyses revealed smaller differences in LOS for H-PA teams and resident-hospitalist teams with the same hospitalist (LOS 5.44% higher, P=0.081).

Conclusions from this study are limited due to lack of randomization of assignment, the retrospective design, and the use of administrative data at one institution.

Bottom line: Hospitalist-PA teams might result in a slightly increased LOS compared with the traditional resident teams; however, inpatient mortality and readmission rates are similar.

Citation: Singh S, Fletcher KE, Schapira MM, et al. A comparison of outcomes of general medical inpatient care provided by a hospitalist-physician assistant model vs a traditional resident-based model. J Hosp Med. 2011;6:122-130.

Washing White Coats Does Not Lower MRSA Bacterial Contamination

Clinical question: Are clean, short-sleeved uniforms less likely to carry MRSA than regularly laundered long-sleeved white coats?

Background: Studies have shown that bacteria frequently colonize in physician garments. However, evidence that short-sleeved garments or newly laundered garments are less likely to be contaminated has been lacking. Despite the paucity of evidence, the British Department of Health barred the use of traditional white coats and long-sleeved garments in 2007.

Study design: Prospective, randomized, controlled trial.

Setting: Urban U.S. hospital.

Synopsis: Study authors randomized 100 internal-medicine residents and hospitalists to their own long-sleeved white coats or freshly laundered short-sleeved uniforms from August 2008 to November 2009. Swabs were taken from the sleeves of the white coats or uniform, the breast pocket, and the volar wrist surface of the dominant hand. Swabs were cultured for MRSA and for general colony count.

Results showed no significant difference in colony counts or MRSA colonization in any of the sites tested between the newly laundered uniforms and the white coats. Additionally, there was no effect in relation to the frequency of laundering the white coats. Notably, within three hours of donning freshly laundered uniforms, bacterial counts approached 50% of the total bacterial counts seen at eight hours.

Bottom line: Laundering of uniforms does not affect MRSA colonization rate or general bacterial burden on physician uniforms or skin surfaces, though the effect on nosocomial infection has not been established.

Citation: Burden M, Cervantes L, Weed D, Keniston A, Price CS, Albert RK. Newly cleaned physician uniforms and infrequently washed white coats have similar rates of bacterial contamination after an 8-hour workday: a randomized controlled trial. J Hosp Med. 2011;6:177-182.

Self-Reported Pain Severity Does Not Correlate with Heart Rate or Blood Pressure Measurements in Pre-Hospital Setting

Clinical question: Do measured vital signs, including heart rate, blood pressure, and respiratory rate, correlate with the degree of self-reported pain?

Background: Because pain often can be associated with alterations in autonomic tone, it has been hypothesized that alterations in vital signs will occur in patients who report pain.

Study design: Retrospective cohort study.

Setting: Pre-hospital in Melbourne, Australia.

Synopsis: The authors reviewed all ambulance patient care records for patients age >14 years with a Glasgow Coma Score (GCS) >12 transported to a hospital during a seven-day period in 2005. Patients were selected for analysis if their patient care record included an initial assessment of pain severity, as measured by a numeric rating scale (NRS), in which patients rate their pain from 0 to 10.

More than half of the 3,357 patients transported by paramedics during the period were included in this analysis (n=1286). There was no correlation between heart rate or systolic blood pressure with the degree of self-reported pain. Although an increased respiratory rate was statistically correlated with a higher rating of pain, this relationship was not clinically significant, as each one-point increase in the pain rating scale was associated with a 0.16-breaths-per-minute increase in the respiratory rate.

Limitations included the large number of records excluded from analysis because pain was not evaluated, as well as numerous unmeasured confounders, including active disease processes such as sepsis, that were not accounted for.

Bottom line: Severity of pain did not correlate with heart rate or systolic blood pressure in the pre-hospital setting.

Citation: Lord B, Woollard M. The reliability of vital signs in estimating pain severity among adult patients treated by paramedics. Emerg Med J. 2011;28:147-150.

Asymptomatic Perioperative Myocardial Infarction Is Common in Patients Undergoing Noncardiac Surgery

Clinical question: In patients undergoing noncardiac surgery, what is the incidence and clinical characteristics of perioperative myocardial infarction (MI)?

Background: Though millions of patients experience perioperative MI after noncardiac surgery, little is known about the characteristics and outcomes of these patients.

Study design: Cohort study.

Setting: One hundred ninety centers in 23 countries.

Synopsis: Using data from the 8,351 patients in the POISE (PeriOperative ISchemic Evaluation) trial, this study showed that perioperative MI occurred in 5% of patients; 65% were asymptomatic. Patients who experienced postoperative MI were older and had more cardiovascular risk factors when compared to those who did not. The 30-day mortality was higher in patients with a perioperative MI (11.6%) compared with those who did not (2.2%); the presence or absence of ischemic symptoms was not associated with mortality rate.

Of the 8.3% of patients who experienced an elevation in cardiac biomarkers but who did not meet the definition of MI, there was an increased risk of nonfatal cardiac arrest and nonacute coronary revascularization. Those in the highest quartile also had increased 30-day mortality.

Bottom line: Given the high proportion of asymptomatic MIs and isolated elevations in cardiac biomarkers and the association between these events and increased risk of death, hospitalists should consider routine monitoring of troponin in at-risk patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154(8):523-528.

Patients Prescribed Higher Opioid Doses Are at Increased Risk of Opioid Overdose Death

Clinical question: What is the association between opioid prescribing patterns and fatal opioid overdose?

Background: In the past 10 years, the rate of fatal overdose from opioid prescription for pain has more than doubled. Little is known about how the indications (substance abuse disorders, cancer-related pain, chronic pain, acute pain), maximal daily dose, and scheduling (standing, as-needed, or both) of opioid prescriptions relate to this increased risk.

Study design: Case-cohort study.

Setting: Veterans Health Administration (VHA) patients.

Synopsis: The VHA’s National Patient Care Database was used to randomly select a cohort of 154,684 nonhospice/nonpalliative-care patients who were prescribed opioids from 2004 to 2008. They were compared with 750 patients who were treated with prescription opioids who died from opioid overdose during this time.

Fatal opioid overdose was a rare event (0.04%), but risk increased with higher prescribed maximum daily morphine dose-equivalence, especially when greater than or equal to 50 mg/day in all subgroups (substance abuse, acute and chronic pain, and cancer). Fatal overdoses were higher in middle-aged white men with acute or chronic pain, substance abuse disorders, and other psychiatric illness. Patients with cancer were at increased risk of fatal overdose if they were prescribed as-needed opioids alone.

Treatment with both as-needed and standing opioids did not statistically affect risk of overdose death in any subgroup.

Bottom line: Although rare, risk of fatal opioid overdose in patients prescribed opiate medication increases with higher maximum prescribed daily dose.

Citation: Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-1321.

Structured Interdisciplinary Rounds on Medical Teaching Unit Significantly Decrease Adverse Events

Clinical question: Do structured interdisciplinary rounds have an impact on the rate of adverse events?

Background: Many preventable adverse events occurring during hospitalization can be attributed to communication failures. Structured interdisciplinary rounds provide a format as well as a forum for team members to discuss patient care. Prior studies demonstrated improvements in collaboration; whether this translates to better patient care is not known.

Study design: Retrospective cohort using historic and concurrent control.

Setting: Tertiary-care teaching hospital in Chicago.

Synopsis: Structured interdisciplinary rounds, led by a nurse manager and medical director, and including nurses, residents, pharmacists, social workers, and case managers, were implemented on a medical teaching unit. New patients were discussed using a structured communication tool; existing patients were discussed in an unstructured format. Medical records were abstracted for 370 patients hospitalized after implementation of the intervention, equally divided between intervention and control units. One hundred eighty-five patients hospitalized on the intervention unit prior to the implementation of rounds served as a historic control.

Patients in the intervention unit had significantly lower rates of total adverse events (3.9 per 100 patient days in the intervention, compared with 7.2 and 7.7 per 100 patient days for the concurrent and historic control units, respectively), and preventable adverse events (0.9 per 100 patient days, compared with 2.8 and 2.1 per 100 patient days for the concurrent and historic controls, respectively).

Limitations of the study include lack of blinding of the medical record, slightly different patient populations in intervention and control groups, and the one-hospital setting, which could limit generalizability.

Bottom line: Structured interdisciplinary rounds might serve to improve communication between nurses, pharmacists, and physicians, resulting in decreases in adverse events.

Citation: O’Leary KJ, Buck R, Fligiel HM, et al. Structured interdisciplinary rounds in a medical teaching unit: improving patient safety. Arch Intern Med. 2011;171(7):678-684.

Pediatric HM Literature

Short-Course Antibiotic Therapy Effective for Bacterial Meningitis

Clinical question: Is five days of parenteral ceftriaxone as effective as 10 days for the treatment of bacterial meningitis in children?

Background: Morbidity and mortality in bacterial meningitis remain high, particularly in developing countries. Antibiotics are effective treatment, yet the optimal duration of treatment remains uncertain. Some data support a shorter duration of treatment (three to five days).

Study design: Multicountry, double-blind, placebo-controlled, randomized equivalence study.

Setting: Ten pediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam.

Synopsis: Children aged two months to 12 years with bacterial meningitis (due to Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis, or culture-negative with indicative cerebrospinal fluid findings) and without complicating medical conditions were enrolled at participating centers. All children received 80 mg/kg to 100 mg/kg of parenteral ceftriaxone daily and a repeat lumbar puncture 48 to 72 hours after initiation of therapy.

Ultimately, 1,004 children without resistant organisms, persistently positive cultures, or suppurative complications were randomized on day five of therapy to placebo or continuance of ceftriaxone for five more days.

No bacteriologic failures (primary endpoint) were evident with either five or 10 days of treatment.

In addition, no statistically significant differences were found between the groups with respect to clinical treatment failure, hearing loss, neurological sequelae, or death. Secondary analysis by organism revealed similar results.

The primary limitation of this study is that it occurred in developing countries with a fair incidence of H. influenzae meningitis and a low rate of third-generation cephalosporin resistance.

However, pneumococcal and meningococcal disease remained prominent, and this study suggests that clinically stable patients might be treated with a shorter course of parenteral ceftriaxone therapy than currently is recommended.

Bottom line: Five days of ceftriaxone is as effective as 10 days for uncomplicated bacterial meningitis in children.

Citation: Molyneux E, Nizami SQ, Saha S, et al. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Lancet. 2011;377:1837-1845.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is dalteparin better than unfractionated heparin at preventing venous thromboembolism (VTE) in ICU patients?

Background: VTE is an important health problem for critically ill patients, but prevention is possible, with both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) superior to placebo in previous studies. Studies comparing UFH and LMWH in ICU patients have been inconclusive thus far.

Study design: Randomized controlled trial.

Setting: Sixty-seven ICUs in six countries from 2006 to 2010.

Synopsis: Researchers randomized 3,746 patients who met the enrollment criteria to either the LMWH dalteparin 5,000 units daily or UFH 5,000 IU twice daily. The drug was held if major bleeding occurred or the patient developed thrombocytopenia concerning heparin-induced thrombocytopenia (HIT). Patients were followed until discharge or death. VTE was evaluated by ultrasound two days after ICU admission and then twice weekly.

There was no difference in incidence of VTE in patients receiving dalteparin versus UFH [5.1% vs. 5.8%, HR 0.92 (CI 0.68-1.23), P=0.57]. Fewer pulmonary emboli occurred in the dalteparin group (1.3% vs. 2.3%, HR 0.51, P=0.01). There was no difference in major bleeding or HIT between groups.

Bottom line: Dalteparin and UFH were equally effective at preventing proximal VTE in ICU patients, but dalteparin prevented more pulmonary emboli.

Citation: The PROTECT investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2010;364(14):1305-1314.

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

Clinical question: Is dalteparin better than unfractionated heparin at preventing venous thromboembolism (VTE) in ICU patients?

Background: VTE is an important health problem for critically ill patients, but prevention is possible, with both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) superior to placebo in previous studies. Studies comparing UFH and LMWH in ICU patients have been inconclusive thus far.

Study design: Randomized controlled trial.

Setting: Sixty-seven ICUs in six countries from 2006 to 2010.

Synopsis: Researchers randomized 3,746 patients who met the enrollment criteria to either the LMWH dalteparin 5,000 units daily or UFH 5,000 IU twice daily. The drug was held if major bleeding occurred or the patient developed thrombocytopenia concerning heparin-induced thrombocytopenia (HIT). Patients were followed until discharge or death. VTE was evaluated by ultrasound two days after ICU admission and then twice weekly.

There was no difference in incidence of VTE in patients receiving dalteparin versus UFH [5.1% vs. 5.8%, HR 0.92 (CI 0.68-1.23), P=0.57]. Fewer pulmonary emboli occurred in the dalteparin group (1.3% vs. 2.3%, HR 0.51, P=0.01). There was no difference in major bleeding or HIT between groups.

Bottom line: Dalteparin and UFH were equally effective at preventing proximal VTE in ICU patients, but dalteparin prevented more pulmonary emboli.

Citation: The PROTECT investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2010;364(14):1305-1314.

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

Clinical question: Is dalteparin better than unfractionated heparin at preventing venous thromboembolism (VTE) in ICU patients?

Background: VTE is an important health problem for critically ill patients, but prevention is possible, with both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) superior to placebo in previous studies. Studies comparing UFH and LMWH in ICU patients have been inconclusive thus far.

Study design: Randomized controlled trial.

Setting: Sixty-seven ICUs in six countries from 2006 to 2010.

Synopsis: Researchers randomized 3,746 patients who met the enrollment criteria to either the LMWH dalteparin 5,000 units daily or UFH 5,000 IU twice daily. The drug was held if major bleeding occurred or the patient developed thrombocytopenia concerning heparin-induced thrombocytopenia (HIT). Patients were followed until discharge or death. VTE was evaluated by ultrasound two days after ICU admission and then twice weekly.

There was no difference in incidence of VTE in patients receiving dalteparin versus UFH [5.1% vs. 5.8%, HR 0.92 (CI 0.68-1.23), P=0.57]. Fewer pulmonary emboli occurred in the dalteparin group (1.3% vs. 2.3%, HR 0.51, P=0.01). There was no difference in major bleeding or HIT between groups.

Bottom line: Dalteparin and UFH were equally effective at preventing proximal VTE in ICU patients, but dalteparin prevented more pulmonary emboli.

Citation: The PROTECT investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2010;364(14):1305-1314.

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

In This Edition

Literature at a Glance

A guide to this month’s studies

• Antibiotics after drainage of uncomplicated skin abscesses
• Clopidogrel vs. combined aspirin-dipyridamole for acute ischemic stroke
• BNP-guided therapy in chronic heart failure outpatients
• Cognitive decline and dementia after hospitalization
• Clopidogrel delays up risks for DES implantation patients
• Clinical score identifies prolonged length of stay
• Time to therapy reduces mortality in sepsis patients
• PEEP associated with lower mortality for ARDS patients

Antibiotics Might Be Unnecessary after Drainage of Uncomplicated Skin Abscesses

Clinical question: Does trimethoprim/sulfamethoxazole (TMP/SMX) treatment after drainage of a skin abscess reduce treatment failure at seven days or development of new lesions at 30 days?

Background: Community ac-quired methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses are increasing in frequency. The benefit of antibiotic treatment after incision and drainage is not clear, as there is a high cure rate without antibiotics.

Study design: Multicenter, double-blinded, randomized, placebo-controlled trial.

Setting: Four military EDs treating civilians and military patients.

Synopsis: The study enrolled a convenience sample of 220 patients, each of whom presented to EDs with uncomplicated skin abscesses from November 2007 to June 2009. Abscesses were drained in the ED, then patients were randomized to either placebo or to TMP/SMX (two DS tablets twice daily) for seven days. Re-evaluation for wound checks occurred at two days and seven days.

Treatment failure at seven days, defined as worsening infection, new lesions, or absence of clinical improvement, occurred in 26% of placebo patients and 17% of patients in the treatment arm, a nonsignificant difference (P=0.12). Fewer patients in the treatment arm had new lesions at 30 days (28% vs. 9%, P=0.02). MRSA was cultured from 53% of patients overall; all samples were sensitive to TMP/SMX.

The study was limited by the fact that only 69% of patients were evaluated at 30 days.

Bottom line: TMP/SMX treatment of uncomplicated skin abscess after drainage in EDs does not decrease treatment failure at seven days, but might decrease the development of new lesions.

Citation: Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection [published online ahead of print March 29, 2010]. Ann Emerg Med. doi:10.1016/j.annemerg med.2010.03.002.

Clopidogrel and Combined Aspirin-Dipyridamole Have Similar Safety and Efficacy Profiles for Acute Ischemic Stroke

Clinical question: What is the efficacy and safety of combined aspirin and extended-release dipyridamole (Asp/ER-DP) compared to clopidogrel in patients with acute ischemic stroke?

Background: Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of Asp/ER-DP or clopidogrel is not known in patients with acute ischemic stroke.

Study design: Randomized, controlled trial.

Setting: A multicenter trial involving 695 sites in 35 countries.

Synopsis: This post-hoc subgroup analysis of the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial assessed the relative safety and efficacy of Asp/ER-DP versus clopidogrel administered within 72 hours of stroke onset in 1,360 patients. The primary endpoint was functional outcome at 30 days.

Secondary outcomes included symptomatic hemorrhagic transformation of the infarct, cerebral edema, recurrent stroke, myocardial infarction (MI), composite vascular events (combination of nonfatal stroke, nonfatal MI, and vascular death), death, cognition, bleeding, and serious adverse events studied at seven, 30, and 90 days.

Combined death or dependency did not differ between treatment groups. Nonsignificant trends to reduced recurrence and vascular events were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups.

Bottom line: Either clopidogrel or combined aspirin and extended-release dipyridamole can be used to treat acute ischemic stroke, with similar outcomes and safety profiles.

Citation: Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis. Stroke. 2010;41(4):732-738.

BNP-Guided Therapy Reduces All-Cause Mortality in Outpatients with Chronic Heart Failure

Clinical question: Is there a clinical benefit in using B-type natriuretic peptide (BNP) to guide adjustment of proven medications in chronic heart failure?

Background: BNP is secreted by the heart in response to increased volume. It has been shown to be useful in the diagnosis of decompensated heart failure, and it can be decreased by treatment with proven heart failure medications. It is unclear if this effect provides clinical benefit on mortality and hospitalization.

Study design: Meta-analysis of prospective randomized controlled trials.

Setting: Eight studies involving 1,726 patients, published internationally from 2005-2009.

Synopsis: Study sizes ranged from 41 to 499 patients, with three- to 24-month follow-up. Patients had New York Heart Association (NYHA) class II or greater heart failure, with ejection fractions <50%.

All-cause mortality was significantly lower in BNP-guided therapy compared with clinical-guided therapy (RR=0.76; 95% CI, 0.63-0.91; P=0.003), specifically in patients younger than 75 years old (RR=0.52; 95% CI, 0.33-0.82; P=0.005).

A proposed mechanism for this result was a statistically significant increase in adjustment of most heart failure medications for BNP-guided therapy compared with clinical-guided therapy (75% vs. 58%, P<0.001 in diuretics; 49.6% vs. 30.9%, P<0.001 in ACE inhibitors or Angiotensin II receptor blockers (ARBs); and 51.1% vs. 41.6%, P=0.02 in beta-blockers) and a higher percentage reaching target doses in the BNP-guided therapy group. However, there was no significant decrease in all-cause hospitalization or survival free of hospitalization.

The study limitations include: Hospitalization for heart failure was not meta-analyzed, the pooled data were weighted toward one study, and BNP-guided titration parameters varied across studies.

Bottom line: BNP-guided therapy reduces all-cause mortality in chronic heart failure patients younger than 75 years old, but not all-cause hospitalization or survival free of hospitalization.

Citation: Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med. 2010;170(6):507-514.

Hospitalization Is Associated with Cognitive Decline and Subsequent Risk for Dementia in the Elderly

Clinical question: Is critical illness in patients 65 and older associated with long-term cognitive impairment, and does it affect the incidence of dementia?

Background: There is literature suggesting that survivors of critical illness suffer long-term cognitive impairment, but premorbid measures of cognitive function have not been researched. No studies have evaluated the risk of incident dementia among this patient population.

Study design: Prospective cohort study.

Setting: Group Health Cooperative in Seattle.

Synopsis: This study analyzed data from 2,929 community-dwelling adults older than 65 without baseline dementia. From 1994 to 2007, the individuals were screened with the Cognitive Abilities Screening Instrument (CASI) at follow-up visits every two years. CASI scores lower than 86 (out of 100) led to an examination for dementia; the diagnosis of dementia was an outcome measure. Scores were adjusted for baseline cognitive scores, age, and other risk factors.

For patients following acute-care hospitalization, adjusted CASI scores were 1.01 points lower on average than for those not hospitalized. For patients following critical-illness hospitalization, scores were 2.14 points lower. The dementia rate was 14.6 cases per 1,000 person-years among patients not hospitalized, and 33.6 among those admitted for noncritical illness.

As suspected, hospitalization might be a marker for cognitive decline in the elderly after adjusting for premorbid CASI scores and comorbid illness. Some factors in acute illness—and moreso in critical illness—might be causally related to cognitive decline.

Bottom line: In elderly patients without dementia at baseline, hospitalization for acute care and critical illness increases the likelihood of cognitive decline compared with patients who were not hospitalized. Only noncritical-illness hospitalization was not associated with the development of dementia.

Citation: Ehlenbach WJ, Hough CL, Crane PK, et al. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA. 2010;303(8): 763-770.

Increased Risk of Death and Myocardial Infarction in Patients Who Delay Filling Clopidogrel Prescription after Drug-Eluting Stent Implantation

Clinical question: Is there an increased risk of death or myocardial infarction (MI) in patients with recent drug-eluting stent (DES) implantation who delayed filling their clopidogrel prescription compared with those who filled their prescription on the day of hospital discharge?

Background: Filling an initial prescription of clopidogrel on the day of discharge is important after DES implantation, as prior studies suggest that lack of thienopyridine therapy is a risk factor for early stent thrombosis.

Study design: Retrospective cohort study.

Setting: Three large, integrated healthcare systems.

Synopsis: The cohort included 7,042 patients discharged after DES implantation. Filling of a clopidogrel prescription was based on pharmacy dispensing data. Primary analysis divided patients based on whether they filled the prescription on the day of discharge or any time after discharge. Secondary analysis further characterized delays as >1 day, >3 days, or >5 days after discharge.

One in 6 patients delayed filling the initial prescription. Patients with any degree of delay had significantly higher death and MI rates during follow-up (14.2% vs. 7.9%, P<0.001), as well as an increased risk of death/MI (hazard ratio 1.53; 95% CI, 1.25-1.87). Factors associated with a delay in filling clopidogrel included older age, prior MI, diabetes, renal dysfunction, prior revascularization, cardiogenic shock, in-hospital bleeding, and use of clopidogrel upon admission.

The study was limited in that data were based on pharmacy records, and that patients might have received medication at discharge or outside the healthcare system.

Bottom line: The delay in filling a clopidogrel prescription is associated with an increased risk of death and MI in patients with recent DES implantation.

Citation: Ho PM, Tsai TT, Maddox TM, et al. Delays in filling clopidogrel prescription after hospital discharge and adverse outcomes after drug-eluting stent implantation: implications for transitions of care. Circ Cardiovasc Qual Outcomes. 2010;3(3):261-266.

Predicting Length of Stay after Stroke

Clinical question: Does a clinical score accurately predict prolonged length of stay after stroke?

Background: Stroke is a costly health problem, and length of stay is the most prominent factor contributing to the high costs. The factors leading to prolonged length of stay are varied, and there are no established tools to predict length of stay.

Study design: Prospective cohort study.

Setting: All 28 Israeli hospitals that admit stroke patients.

Synopsis: All patients admitted to Israeli hospitals during established two-month periods in 2004 (1,700 patients) and 2007 (1,648 patients) were included in the National Acute Stroke Israeli Survey (NASIS), and served as the derivation and validation cohort for development of a Prolonged Length of Stay (PLOS) score.

Using the 2004 data, investigators identified stroke severity using the National Institutes of Health Stroke Scale (NIHSS), history of congestive heart failure (CHF), history of atrial fibrillation, decreased level of consciousness on presentation, and intracerebral hemorrhage (as opposed to ischemic stroke) as predictors of prolonged length of stay. Four of these factors were expressed as dichotomous variables, whereas the stroke severity by NIHSS class was incorporated as a range; all were incorporated into a PLOS score.

Higher PLOS score correlated with longer length of stay. In the derivation cohort, 22% of patients with a PLOS score of 0 had a prolonged length of stay, whereas 85% of patients with PLOS scores of 6 or 7 had a prolonged length of stay. In the validation cohort, the corresponding figures were 19% and 72%.

Bottom line: Use of a simple score can predict risk of prolonged length of stay after stroke.

Citation: Koton S, Bornstein NM, Tsabari R, Tanne D, NASIS Investigators. Derivation and validation of the prolonged length of stay score in acute stroke patients. Neurology. 2010;74(19);1511-1516.

Earlier Administration of Appropriate Antimicrobials Decreases Mortality in Patients with Severe Sepsis and Septic Shock

Clinical question: Is the timing of antimicrobial administration an important determinant of survival in patients diagnosed with severe sepsis and septic shock?

Background: Severe sepsis and septic shock are associated with a 25% to 50% mortality rate. Early goal-directed therapy has been shown to increase survival in these patients. Antimicrobial treatment is a mainstay of this therapy, but the most effective timing of this treatment remains unclear.

Study design: Retrospective, single-center cohort study.

Setting: ED at an academic tertiary-care center.

Synopsis: Two hundred sixty-one patients in the ED in 2005-2006 presenting with severe sepsis or septic shock were enrolled in the hospital’s early goal-directed therapy (EGDT) algorithm, either at triage or later during their ED stay. Labs showed 56.7% of patients were culture-positive, with the most common sources being respiratory (30.6%), genitourinary (22.8%), and gastrointestinal (19.7%).

All patients received antibiotics and were stratified in one-hour intervals by the following categories: time from triage to antibiotics; time from qualification for EGDT to antibiotics; time from triage to appropriate antibiotics; and time from qualification for EGDT to appropriate antibiotics.

Total in-hospital mortality was 31% (35.1% for culture-positive patients vs. 25.7% for culture-negative patients, P=0.11). A significant decrease in mortality was only found when appropriate antibiotics were administered within one hour of triage, or within one hour of qualification for EGDT (OR=0.30; 95% CI, 0.11-0.83; P=0.02, and OR=0.50; 95% CI, 0.27-0.92; P=0.03, respectively).

Study limitations included the single-center site and small sample size.

Bottom line: In patients with severe sepsis and septic shock, initiating appropriate antimicrobial therapy within one hour of triage or entry into goal-directed therapy significantly reduces mortality.

Citation: Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053.

Treatment with Higher Levels of Positive End-Expiratory Pressure Has Limited Affect on Hospital Survival

Clinical question: Is treatment with higher versus lower levels of positive end-expiratory pressure (PEEP) associated with improved hospital survival?

Background: In the management of patients with acute lung injury or acute respiratory distress syndrome (ARDS), a fundamental goal is to protect the lungs from ventilation-induced injury, but the optimal PEEP level has not been established.

Study design: Systematic review and meta-analysis.

Setting: N/A.

Synopsis: Three randomized-controlled trials eligible for this review included 2,299 critically ill adults with acute lung injury, as defined by the American-European Consensus Conference. The meta-analysis compared higher and lower PEEP levels with a mean difference of at least 3 cm H2O, incorporated a target tidal volume of less than 8 mL/kg of predicted body weight in both ventilation strategies, and provided patient follow-up until death or for at least 20 days.

This review demonstrated no statistically significant difference in hospital mortality between the groups. However, in patients with ARDS, higher levels of PEEP were associated with a relative reduction in mortality of 10%. This is supported by a recent cohort study in patients with acute lung injury or ARDS, which showed that the effect of PEEP on lung recruitment was associated with the proportion of potentially recruitable lung, as determined by computed tomography.

Since patients with ARDS have more pulmonary edema than those with acute lung injury without ARDS, the former have greater recruitability, and thus might benefit more from higher levels of PEEP.

Bottom line: Higher levels of PEEP might be associated with lower hospital mortality in patients with ARDS, but such a benefit is unlikely in patients with less severe lung injuries, and could actually be harmful.

Citation: Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865-873. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

High-Performing State Healthcare Systems Have Higher Children’s Hospital Readmission Rates

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What is the relationship between a hospital’s readmission rate and performance of the surrounding healthcare system?

Background: Hospital readmission rates might be influenced by factors related to the specific patient and hospital care, as well as such external factors as the performance of the surrounding healthcare system. Traditionally, readmission rates are thought to most accurately reflect the quality of hospital care; however, the relative contributions of patient, hospital, and external factors to hospital readmission rates have not been delineated.

Study design: Multilevel cohort study.

Setting: Thirty-nine children’s hospitals in 24 states.

Synopsis: The Pediatric Health Information System (PHIS) administrative database was sampled for the 2005 calendar year to review discharges from 39 participating children’s hospitals. Patients 2 to 18 years were included, and out of a total of 198,422 patients, 32,196 were readmitted within 365 days of discharge.

The Commonwealth Fund’s 2008 State Variations in Child Health System Performance ranking was used to define the state-level health system performance. Higher readmission rates correlated with higher-ranked state child health systems after adjustment for patient-level characteristics.

This surprising result calls into question the often-assumed link between hospital readmission rates and poor systems of care. However, despite the strength of its large sample size, this study’s macro-level view of the healthcare system might be too crude to truly define the external factors that play a role in readmission. State-level healthcare rankings might not accurately reflect the healthcare ecosystem surrounding each children’s hospital, and children’s hospitals do not care for the majority of children in the U.S.

Bottom line: Children’s hospital readmissions correlate with higher state child health system performance.

Citation: Feudtner C, Pati S, Goodman DM, et al. State-level child health system performance and the likelihood of readmission to children’s hospitals. J Pediatr. 2010;157(1):98-102.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Antibiotics after drainage of uncomplicated skin abscesses
• Clopidogrel vs. combined aspirin-dipyridamole for acute ischemic stroke
• BNP-guided therapy in chronic heart failure outpatients
• Cognitive decline and dementia after hospitalization
• Clopidogrel delays up risks for DES implantation patients
• Clinical score identifies prolonged length of stay
• Time to therapy reduces mortality in sepsis patients
• PEEP associated with lower mortality for ARDS patients

Antibiotics Might Be Unnecessary after Drainage of Uncomplicated Skin Abscesses

Clinical question: Does trimethoprim/sulfamethoxazole (TMP/SMX) treatment after drainage of a skin abscess reduce treatment failure at seven days or development of new lesions at 30 days?

Background: Community ac-quired methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses are increasing in frequency. The benefit of antibiotic treatment after incision and drainage is not clear, as there is a high cure rate without antibiotics.

Study design: Multicenter, double-blinded, randomized, placebo-controlled trial.

Setting: Four military EDs treating civilians and military patients.

Synopsis: The study enrolled a convenience sample of 220 patients, each of whom presented to EDs with uncomplicated skin abscesses from November 2007 to June 2009. Abscesses were drained in the ED, then patients were randomized to either placebo or to TMP/SMX (two DS tablets twice daily) for seven days. Re-evaluation for wound checks occurred at two days and seven days.

Treatment failure at seven days, defined as worsening infection, new lesions, or absence of clinical improvement, occurred in 26% of placebo patients and 17% of patients in the treatment arm, a nonsignificant difference (P=0.12). Fewer patients in the treatment arm had new lesions at 30 days (28% vs. 9%, P=0.02). MRSA was cultured from 53% of patients overall; all samples were sensitive to TMP/SMX.

The study was limited by the fact that only 69% of patients were evaluated at 30 days.

Bottom line: TMP/SMX treatment of uncomplicated skin abscess after drainage in EDs does not decrease treatment failure at seven days, but might decrease the development of new lesions.

Citation: Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection [published online ahead of print March 29, 2010]. Ann Emerg Med. doi:10.1016/j.annemerg med.2010.03.002.

Clopidogrel and Combined Aspirin-Dipyridamole Have Similar Safety and Efficacy Profiles for Acute Ischemic Stroke

Clinical question: What is the efficacy and safety of combined aspirin and extended-release dipyridamole (Asp/ER-DP) compared to clopidogrel in patients with acute ischemic stroke?

Background: Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of Asp/ER-DP or clopidogrel is not known in patients with acute ischemic stroke.

Study design: Randomized, controlled trial.

Setting: A multicenter trial involving 695 sites in 35 countries.

Synopsis: This post-hoc subgroup analysis of the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial assessed the relative safety and efficacy of Asp/ER-DP versus clopidogrel administered within 72 hours of stroke onset in 1,360 patients. The primary endpoint was functional outcome at 30 days.

Secondary outcomes included symptomatic hemorrhagic transformation of the infarct, cerebral edema, recurrent stroke, myocardial infarction (MI), composite vascular events (combination of nonfatal stroke, nonfatal MI, and vascular death), death, cognition, bleeding, and serious adverse events studied at seven, 30, and 90 days.

Combined death or dependency did not differ between treatment groups. Nonsignificant trends to reduced recurrence and vascular events were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups.

Bottom line: Either clopidogrel or combined aspirin and extended-release dipyridamole can be used to treat acute ischemic stroke, with similar outcomes and safety profiles.

Citation: Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis. Stroke. 2010;41(4):732-738.

BNP-Guided Therapy Reduces All-Cause Mortality in Outpatients with Chronic Heart Failure

Clinical question: Is there a clinical benefit in using B-type natriuretic peptide (BNP) to guide adjustment of proven medications in chronic heart failure?

Background: BNP is secreted by the heart in response to increased volume. It has been shown to be useful in the diagnosis of decompensated heart failure, and it can be decreased by treatment with proven heart failure medications. It is unclear if this effect provides clinical benefit on mortality and hospitalization.

Study design: Meta-analysis of prospective randomized controlled trials.

Setting: Eight studies involving 1,726 patients, published internationally from 2005-2009.

Synopsis: Study sizes ranged from 41 to 499 patients, with three- to 24-month follow-up. Patients had New York Heart Association (NYHA) class II or greater heart failure, with ejection fractions <50%.

All-cause mortality was significantly lower in BNP-guided therapy compared with clinical-guided therapy (RR=0.76; 95% CI, 0.63-0.91; P=0.003), specifically in patients younger than 75 years old (RR=0.52; 95% CI, 0.33-0.82; P=0.005).

A proposed mechanism for this result was a statistically significant increase in adjustment of most heart failure medications for BNP-guided therapy compared with clinical-guided therapy (75% vs. 58%, P<0.001 in diuretics; 49.6% vs. 30.9%, P<0.001 in ACE inhibitors or Angiotensin II receptor blockers (ARBs); and 51.1% vs. 41.6%, P=0.02 in beta-blockers) and a higher percentage reaching target doses in the BNP-guided therapy group. However, there was no significant decrease in all-cause hospitalization or survival free of hospitalization.

The study limitations include: Hospitalization for heart failure was not meta-analyzed, the pooled data were weighted toward one study, and BNP-guided titration parameters varied across studies.

Bottom line: BNP-guided therapy reduces all-cause mortality in chronic heart failure patients younger than 75 years old, but not all-cause hospitalization or survival free of hospitalization.

Citation: Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med. 2010;170(6):507-514.

Hospitalization Is Associated with Cognitive Decline and Subsequent Risk for Dementia in the Elderly

Clinical question: Is critical illness in patients 65 and older associated with long-term cognitive impairment, and does it affect the incidence of dementia?

Background: There is literature suggesting that survivors of critical illness suffer long-term cognitive impairment, but premorbid measures of cognitive function have not been researched. No studies have evaluated the risk of incident dementia among this patient population.

Study design: Prospective cohort study.

Setting: Group Health Cooperative in Seattle.

Synopsis: This study analyzed data from 2,929 community-dwelling adults older than 65 without baseline dementia. From 1994 to 2007, the individuals were screened with the Cognitive Abilities Screening Instrument (CASI) at follow-up visits every two years. CASI scores lower than 86 (out of 100) led to an examination for dementia; the diagnosis of dementia was an outcome measure. Scores were adjusted for baseline cognitive scores, age, and other risk factors.

For patients following acute-care hospitalization, adjusted CASI scores were 1.01 points lower on average than for those not hospitalized. For patients following critical-illness hospitalization, scores were 2.14 points lower. The dementia rate was 14.6 cases per 1,000 person-years among patients not hospitalized, and 33.6 among those admitted for noncritical illness.

As suspected, hospitalization might be a marker for cognitive decline in the elderly after adjusting for premorbid CASI scores and comorbid illness. Some factors in acute illness—and moreso in critical illness—might be causally related to cognitive decline.

Bottom line: In elderly patients without dementia at baseline, hospitalization for acute care and critical illness increases the likelihood of cognitive decline compared with patients who were not hospitalized. Only noncritical-illness hospitalization was not associated with the development of dementia.

Citation: Ehlenbach WJ, Hough CL, Crane PK, et al. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA. 2010;303(8): 763-770.

Increased Risk of Death and Myocardial Infarction in Patients Who Delay Filling Clopidogrel Prescription after Drug-Eluting Stent Implantation

Clinical question: Is there an increased risk of death or myocardial infarction (MI) in patients with recent drug-eluting stent (DES) implantation who delayed filling their clopidogrel prescription compared with those who filled their prescription on the day of hospital discharge?

Background: Filling an initial prescription of clopidogrel on the day of discharge is important after DES implantation, as prior studies suggest that lack of thienopyridine therapy is a risk factor for early stent thrombosis.

Study design: Retrospective cohort study.

Setting: Three large, integrated healthcare systems.

Synopsis: The cohort included 7,042 patients discharged after DES implantation. Filling of a clopidogrel prescription was based on pharmacy dispensing data. Primary analysis divided patients based on whether they filled the prescription on the day of discharge or any time after discharge. Secondary analysis further characterized delays as >1 day, >3 days, or >5 days after discharge.

One in 6 patients delayed filling the initial prescription. Patients with any degree of delay had significantly higher death and MI rates during follow-up (14.2% vs. 7.9%, P<0.001), as well as an increased risk of death/MI (hazard ratio 1.53; 95% CI, 1.25-1.87). Factors associated with a delay in filling clopidogrel included older age, prior MI, diabetes, renal dysfunction, prior revascularization, cardiogenic shock, in-hospital bleeding, and use of clopidogrel upon admission.

The study was limited in that data were based on pharmacy records, and that patients might have received medication at discharge or outside the healthcare system.

Bottom line: The delay in filling a clopidogrel prescription is associated with an increased risk of death and MI in patients with recent DES implantation.

Citation: Ho PM, Tsai TT, Maddox TM, et al. Delays in filling clopidogrel prescription after hospital discharge and adverse outcomes after drug-eluting stent implantation: implications for transitions of care. Circ Cardiovasc Qual Outcomes. 2010;3(3):261-266.

Predicting Length of Stay after Stroke

Clinical question: Does a clinical score accurately predict prolonged length of stay after stroke?

Background: Stroke is a costly health problem, and length of stay is the most prominent factor contributing to the high costs. The factors leading to prolonged length of stay are varied, and there are no established tools to predict length of stay.

Study design: Prospective cohort study.

Setting: All 28 Israeli hospitals that admit stroke patients.

Synopsis: All patients admitted to Israeli hospitals during established two-month periods in 2004 (1,700 patients) and 2007 (1,648 patients) were included in the National Acute Stroke Israeli Survey (NASIS), and served as the derivation and validation cohort for development of a Prolonged Length of Stay (PLOS) score.

Using the 2004 data, investigators identified stroke severity using the National Institutes of Health Stroke Scale (NIHSS), history of congestive heart failure (CHF), history of atrial fibrillation, decreased level of consciousness on presentation, and intracerebral hemorrhage (as opposed to ischemic stroke) as predictors of prolonged length of stay. Four of these factors were expressed as dichotomous variables, whereas the stroke severity by NIHSS class was incorporated as a range; all were incorporated into a PLOS score.

Higher PLOS score correlated with longer length of stay. In the derivation cohort, 22% of patients with a PLOS score of 0 had a prolonged length of stay, whereas 85% of patients with PLOS scores of 6 or 7 had a prolonged length of stay. In the validation cohort, the corresponding figures were 19% and 72%.

Bottom line: Use of a simple score can predict risk of prolonged length of stay after stroke.

Citation: Koton S, Bornstein NM, Tsabari R, Tanne D, NASIS Investigators. Derivation and validation of the prolonged length of stay score in acute stroke patients. Neurology. 2010;74(19);1511-1516.

Earlier Administration of Appropriate Antimicrobials Decreases Mortality in Patients with Severe Sepsis and Septic Shock

Clinical question: Is the timing of antimicrobial administration an important determinant of survival in patients diagnosed with severe sepsis and septic shock?

Background: Severe sepsis and septic shock are associated with a 25% to 50% mortality rate. Early goal-directed therapy has been shown to increase survival in these patients. Antimicrobial treatment is a mainstay of this therapy, but the most effective timing of this treatment remains unclear.

Study design: Retrospective, single-center cohort study.

Setting: ED at an academic tertiary-care center.

Synopsis: Two hundred sixty-one patients in the ED in 2005-2006 presenting with severe sepsis or septic shock were enrolled in the hospital’s early goal-directed therapy (EGDT) algorithm, either at triage or later during their ED stay. Labs showed 56.7% of patients were culture-positive, with the most common sources being respiratory (30.6%), genitourinary (22.8%), and gastrointestinal (19.7%).

All patients received antibiotics and were stratified in one-hour intervals by the following categories: time from triage to antibiotics; time from qualification for EGDT to antibiotics; time from triage to appropriate antibiotics; and time from qualification for EGDT to appropriate antibiotics.

Total in-hospital mortality was 31% (35.1% for culture-positive patients vs. 25.7% for culture-negative patients, P=0.11). A significant decrease in mortality was only found when appropriate antibiotics were administered within one hour of triage, or within one hour of qualification for EGDT (OR=0.30; 95% CI, 0.11-0.83; P=0.02, and OR=0.50; 95% CI, 0.27-0.92; P=0.03, respectively).

Study limitations included the single-center site and small sample size.

Bottom line: In patients with severe sepsis and septic shock, initiating appropriate antimicrobial therapy within one hour of triage or entry into goal-directed therapy significantly reduces mortality.

Citation: Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053.

Treatment with Higher Levels of Positive End-Expiratory Pressure Has Limited Affect on Hospital Survival

Clinical question: Is treatment with higher versus lower levels of positive end-expiratory pressure (PEEP) associated with improved hospital survival?

Background: In the management of patients with acute lung injury or acute respiratory distress syndrome (ARDS), a fundamental goal is to protect the lungs from ventilation-induced injury, but the optimal PEEP level has not been established.

Study design: Systematic review and meta-analysis.

Setting: N/A.

Synopsis: Three randomized-controlled trials eligible for this review included 2,299 critically ill adults with acute lung injury, as defined by the American-European Consensus Conference. The meta-analysis compared higher and lower PEEP levels with a mean difference of at least 3 cm H2O, incorporated a target tidal volume of less than 8 mL/kg of predicted body weight in both ventilation strategies, and provided patient follow-up until death or for at least 20 days.

This review demonstrated no statistically significant difference in hospital mortality between the groups. However, in patients with ARDS, higher levels of PEEP were associated with a relative reduction in mortality of 10%. This is supported by a recent cohort study in patients with acute lung injury or ARDS, which showed that the effect of PEEP on lung recruitment was associated with the proportion of potentially recruitable lung, as determined by computed tomography.

Since patients with ARDS have more pulmonary edema than those with acute lung injury without ARDS, the former have greater recruitability, and thus might benefit more from higher levels of PEEP.

Bottom line: Higher levels of PEEP might be associated with lower hospital mortality in patients with ARDS, but such a benefit is unlikely in patients with less severe lung injuries, and could actually be harmful.

Citation: Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865-873. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

High-Performing State Healthcare Systems Have Higher Children’s Hospital Readmission Rates

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What is the relationship between a hospital’s readmission rate and performance of the surrounding healthcare system?

Background: Hospital readmission rates might be influenced by factors related to the specific patient and hospital care, as well as such external factors as the performance of the surrounding healthcare system. Traditionally, readmission rates are thought to most accurately reflect the quality of hospital care; however, the relative contributions of patient, hospital, and external factors to hospital readmission rates have not been delineated.

Study design: Multilevel cohort study.

Setting: Thirty-nine children’s hospitals in 24 states.

Synopsis: The Pediatric Health Information System (PHIS) administrative database was sampled for the 2005 calendar year to review discharges from 39 participating children’s hospitals. Patients 2 to 18 years were included, and out of a total of 198,422 patients, 32,196 were readmitted within 365 days of discharge.

The Commonwealth Fund’s 2008 State Variations in Child Health System Performance ranking was used to define the state-level health system performance. Higher readmission rates correlated with higher-ranked state child health systems after adjustment for patient-level characteristics.

This surprising result calls into question the often-assumed link between hospital readmission rates and poor systems of care. However, despite the strength of its large sample size, this study’s macro-level view of the healthcare system might be too crude to truly define the external factors that play a role in readmission. State-level healthcare rankings might not accurately reflect the healthcare ecosystem surrounding each children’s hospital, and children’s hospitals do not care for the majority of children in the U.S.

Bottom line: Children’s hospital readmissions correlate with higher state child health system performance.

Citation: Feudtner C, Pati S, Goodman DM, et al. State-level child health system performance and the likelihood of readmission to children’s hospitals. J Pediatr. 2010;157(1):98-102.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Antibiotics after drainage of uncomplicated skin abscesses
• Clopidogrel vs. combined aspirin-dipyridamole for acute ischemic stroke
• BNP-guided therapy in chronic heart failure outpatients
• Cognitive decline and dementia after hospitalization
• Clopidogrel delays up risks for DES implantation patients
• Clinical score identifies prolonged length of stay
• Time to therapy reduces mortality in sepsis patients
• PEEP associated with lower mortality for ARDS patients

Antibiotics Might Be Unnecessary after Drainage of Uncomplicated Skin Abscesses

Clinical question: Does trimethoprim/sulfamethoxazole (TMP/SMX) treatment after drainage of a skin abscess reduce treatment failure at seven days or development of new lesions at 30 days?

Background: Community ac-quired methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses are increasing in frequency. The benefit of antibiotic treatment after incision and drainage is not clear, as there is a high cure rate without antibiotics.

Study design: Multicenter, double-blinded, randomized, placebo-controlled trial.

Setting: Four military EDs treating civilians and military patients.

Synopsis: The study enrolled a convenience sample of 220 patients, each of whom presented to EDs with uncomplicated skin abscesses from November 2007 to June 2009. Abscesses were drained in the ED, then patients were randomized to either placebo or to TMP/SMX (two DS tablets twice daily) for seven days. Re-evaluation for wound checks occurred at two days and seven days.

Treatment failure at seven days, defined as worsening infection, new lesions, or absence of clinical improvement, occurred in 26% of placebo patients and 17% of patients in the treatment arm, a nonsignificant difference (P=0.12). Fewer patients in the treatment arm had new lesions at 30 days (28% vs. 9%, P=0.02). MRSA was cultured from 53% of patients overall; all samples were sensitive to TMP/SMX.

The study was limited by the fact that only 69% of patients were evaluated at 30 days.

Bottom line: TMP/SMX treatment of uncomplicated skin abscess after drainage in EDs does not decrease treatment failure at seven days, but might decrease the development of new lesions.

Citation: Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection [published online ahead of print March 29, 2010]. Ann Emerg Med. doi:10.1016/j.annemerg med.2010.03.002.

Clopidogrel and Combined Aspirin-Dipyridamole Have Similar Safety and Efficacy Profiles for Acute Ischemic Stroke

Clinical question: What is the efficacy and safety of combined aspirin and extended-release dipyridamole (Asp/ER-DP) compared to clopidogrel in patients with acute ischemic stroke?

Background: Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of Asp/ER-DP or clopidogrel is not known in patients with acute ischemic stroke.

Study design: Randomized, controlled trial.

Setting: A multicenter trial involving 695 sites in 35 countries.

Synopsis: This post-hoc subgroup analysis of the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial assessed the relative safety and efficacy of Asp/ER-DP versus clopidogrel administered within 72 hours of stroke onset in 1,360 patients. The primary endpoint was functional outcome at 30 days.

Secondary outcomes included symptomatic hemorrhagic transformation of the infarct, cerebral edema, recurrent stroke, myocardial infarction (MI), composite vascular events (combination of nonfatal stroke, nonfatal MI, and vascular death), death, cognition, bleeding, and serious adverse events studied at seven, 30, and 90 days.

Combined death or dependency did not differ between treatment groups. Nonsignificant trends to reduced recurrence and vascular events were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups.

Bottom line: Either clopidogrel or combined aspirin and extended-release dipyridamole can be used to treat acute ischemic stroke, with similar outcomes and safety profiles.

Citation: Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis. Stroke. 2010;41(4):732-738.

BNP-Guided Therapy Reduces All-Cause Mortality in Outpatients with Chronic Heart Failure

Clinical question: Is there a clinical benefit in using B-type natriuretic peptide (BNP) to guide adjustment of proven medications in chronic heart failure?

Background: BNP is secreted by the heart in response to increased volume. It has been shown to be useful in the diagnosis of decompensated heart failure, and it can be decreased by treatment with proven heart failure medications. It is unclear if this effect provides clinical benefit on mortality and hospitalization.

Study design: Meta-analysis of prospective randomized controlled trials.

Setting: Eight studies involving 1,726 patients, published internationally from 2005-2009.

Synopsis: Study sizes ranged from 41 to 499 patients, with three- to 24-month follow-up. Patients had New York Heart Association (NYHA) class II or greater heart failure, with ejection fractions <50%.

All-cause mortality was significantly lower in BNP-guided therapy compared with clinical-guided therapy (RR=0.76; 95% CI, 0.63-0.91; P=0.003), specifically in patients younger than 75 years old (RR=0.52; 95% CI, 0.33-0.82; P=0.005).

A proposed mechanism for this result was a statistically significant increase in adjustment of most heart failure medications for BNP-guided therapy compared with clinical-guided therapy (75% vs. 58%, P<0.001 in diuretics; 49.6% vs. 30.9%, P<0.001 in ACE inhibitors or Angiotensin II receptor blockers (ARBs); and 51.1% vs. 41.6%, P=0.02 in beta-blockers) and a higher percentage reaching target doses in the BNP-guided therapy group. However, there was no significant decrease in all-cause hospitalization or survival free of hospitalization.

The study limitations include: Hospitalization for heart failure was not meta-analyzed, the pooled data were weighted toward one study, and BNP-guided titration parameters varied across studies.

Bottom line: BNP-guided therapy reduces all-cause mortality in chronic heart failure patients younger than 75 years old, but not all-cause hospitalization or survival free of hospitalization.

Citation: Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med. 2010;170(6):507-514.

Hospitalization Is Associated with Cognitive Decline and Subsequent Risk for Dementia in the Elderly

Clinical question: Is critical illness in patients 65 and older associated with long-term cognitive impairment, and does it affect the incidence of dementia?

Background: There is literature suggesting that survivors of critical illness suffer long-term cognitive impairment, but premorbid measures of cognitive function have not been researched. No studies have evaluated the risk of incident dementia among this patient population.

Study design: Prospective cohort study.

Setting: Group Health Cooperative in Seattle.

Synopsis: This study analyzed data from 2,929 community-dwelling adults older than 65 without baseline dementia. From 1994 to 2007, the individuals were screened with the Cognitive Abilities Screening Instrument (CASI) at follow-up visits every two years. CASI scores lower than 86 (out of 100) led to an examination for dementia; the diagnosis of dementia was an outcome measure. Scores were adjusted for baseline cognitive scores, age, and other risk factors.

For patients following acute-care hospitalization, adjusted CASI scores were 1.01 points lower on average than for those not hospitalized. For patients following critical-illness hospitalization, scores were 2.14 points lower. The dementia rate was 14.6 cases per 1,000 person-years among patients not hospitalized, and 33.6 among those admitted for noncritical illness.

As suspected, hospitalization might be a marker for cognitive decline in the elderly after adjusting for premorbid CASI scores and comorbid illness. Some factors in acute illness—and moreso in critical illness—might be causally related to cognitive decline.

Bottom line: In elderly patients without dementia at baseline, hospitalization for acute care and critical illness increases the likelihood of cognitive decline compared with patients who were not hospitalized. Only noncritical-illness hospitalization was not associated with the development of dementia.

Citation: Ehlenbach WJ, Hough CL, Crane PK, et al. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA. 2010;303(8): 763-770.

Increased Risk of Death and Myocardial Infarction in Patients Who Delay Filling Clopidogrel Prescription after Drug-Eluting Stent Implantation

Clinical question: Is there an increased risk of death or myocardial infarction (MI) in patients with recent drug-eluting stent (DES) implantation who delayed filling their clopidogrel prescription compared with those who filled their prescription on the day of hospital discharge?

Background: Filling an initial prescription of clopidogrel on the day of discharge is important after DES implantation, as prior studies suggest that lack of thienopyridine therapy is a risk factor for early stent thrombosis.

Study design: Retrospective cohort study.

Setting: Three large, integrated healthcare systems.

Synopsis: The cohort included 7,042 patients discharged after DES implantation. Filling of a clopidogrel prescription was based on pharmacy dispensing data. Primary analysis divided patients based on whether they filled the prescription on the day of discharge or any time after discharge. Secondary analysis further characterized delays as >1 day, >3 days, or >5 days after discharge.

One in 6 patients delayed filling the initial prescription. Patients with any degree of delay had significantly higher death and MI rates during follow-up (14.2% vs. 7.9%, P<0.001), as well as an increased risk of death/MI (hazard ratio 1.53; 95% CI, 1.25-1.87). Factors associated with a delay in filling clopidogrel included older age, prior MI, diabetes, renal dysfunction, prior revascularization, cardiogenic shock, in-hospital bleeding, and use of clopidogrel upon admission.

The study was limited in that data were based on pharmacy records, and that patients might have received medication at discharge or outside the healthcare system.

Bottom line: The delay in filling a clopidogrel prescription is associated with an increased risk of death and MI in patients with recent DES implantation.

Citation: Ho PM, Tsai TT, Maddox TM, et al. Delays in filling clopidogrel prescription after hospital discharge and adverse outcomes after drug-eluting stent implantation: implications for transitions of care. Circ Cardiovasc Qual Outcomes. 2010;3(3):261-266.

Predicting Length of Stay after Stroke

Clinical question: Does a clinical score accurately predict prolonged length of stay after stroke?

Background: Stroke is a costly health problem, and length of stay is the most prominent factor contributing to the high costs. The factors leading to prolonged length of stay are varied, and there are no established tools to predict length of stay.

Study design: Prospective cohort study.

Setting: All 28 Israeli hospitals that admit stroke patients.

Synopsis: All patients admitted to Israeli hospitals during established two-month periods in 2004 (1,700 patients) and 2007 (1,648 patients) were included in the National Acute Stroke Israeli Survey (NASIS), and served as the derivation and validation cohort for development of a Prolonged Length of Stay (PLOS) score.

Using the 2004 data, investigators identified stroke severity using the National Institutes of Health Stroke Scale (NIHSS), history of congestive heart failure (CHF), history of atrial fibrillation, decreased level of consciousness on presentation, and intracerebral hemorrhage (as opposed to ischemic stroke) as predictors of prolonged length of stay. Four of these factors were expressed as dichotomous variables, whereas the stroke severity by NIHSS class was incorporated as a range; all were incorporated into a PLOS score.

Higher PLOS score correlated with longer length of stay. In the derivation cohort, 22% of patients with a PLOS score of 0 had a prolonged length of stay, whereas 85% of patients with PLOS scores of 6 or 7 had a prolonged length of stay. In the validation cohort, the corresponding figures were 19% and 72%.

Bottom line: Use of a simple score can predict risk of prolonged length of stay after stroke.

Citation: Koton S, Bornstein NM, Tsabari R, Tanne D, NASIS Investigators. Derivation and validation of the prolonged length of stay score in acute stroke patients. Neurology. 2010;74(19);1511-1516.

Earlier Administration of Appropriate Antimicrobials Decreases Mortality in Patients with Severe Sepsis and Septic Shock

Clinical question: Is the timing of antimicrobial administration an important determinant of survival in patients diagnosed with severe sepsis and septic shock?

Background: Severe sepsis and septic shock are associated with a 25% to 50% mortality rate. Early goal-directed therapy has been shown to increase survival in these patients. Antimicrobial treatment is a mainstay of this therapy, but the most effective timing of this treatment remains unclear.

Study design: Retrospective, single-center cohort study.

Setting: ED at an academic tertiary-care center.

Synopsis: Two hundred sixty-one patients in the ED in 2005-2006 presenting with severe sepsis or septic shock were enrolled in the hospital’s early goal-directed therapy (EGDT) algorithm, either at triage or later during their ED stay. Labs showed 56.7% of patients were culture-positive, with the most common sources being respiratory (30.6%), genitourinary (22.8%), and gastrointestinal (19.7%).

All patients received antibiotics and were stratified in one-hour intervals by the following categories: time from triage to antibiotics; time from qualification for EGDT to antibiotics; time from triage to appropriate antibiotics; and time from qualification for EGDT to appropriate antibiotics.

Total in-hospital mortality was 31% (35.1% for culture-positive patients vs. 25.7% for culture-negative patients, P=0.11). A significant decrease in mortality was only found when appropriate antibiotics were administered within one hour of triage, or within one hour of qualification for EGDT (OR=0.30; 95% CI, 0.11-0.83; P=0.02, and OR=0.50; 95% CI, 0.27-0.92; P=0.03, respectively).

Study limitations included the single-center site and small sample size.

Bottom line: In patients with severe sepsis and septic shock, initiating appropriate antimicrobial therapy within one hour of triage or entry into goal-directed therapy significantly reduces mortality.

Citation: Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045-1053.

Treatment with Higher Levels of Positive End-Expiratory Pressure Has Limited Affect on Hospital Survival

Clinical question: Is treatment with higher versus lower levels of positive end-expiratory pressure (PEEP) associated with improved hospital survival?

Background: In the management of patients with acute lung injury or acute respiratory distress syndrome (ARDS), a fundamental goal is to protect the lungs from ventilation-induced injury, but the optimal PEEP level has not been established.

Study design: Systematic review and meta-analysis.

Setting: N/A.

Synopsis: Three randomized-controlled trials eligible for this review included 2,299 critically ill adults with acute lung injury, as defined by the American-European Consensus Conference. The meta-analysis compared higher and lower PEEP levels with a mean difference of at least 3 cm H2O, incorporated a target tidal volume of less than 8 mL/kg of predicted body weight in both ventilation strategies, and provided patient follow-up until death or for at least 20 days.

This review demonstrated no statistically significant difference in hospital mortality between the groups. However, in patients with ARDS, higher levels of PEEP were associated with a relative reduction in mortality of 10%. This is supported by a recent cohort study in patients with acute lung injury or ARDS, which showed that the effect of PEEP on lung recruitment was associated with the proportion of potentially recruitable lung, as determined by computed tomography.

Since patients with ARDS have more pulmonary edema than those with acute lung injury without ARDS, the former have greater recruitability, and thus might benefit more from higher levels of PEEP.

Bottom line: Higher levels of PEEP might be associated with lower hospital mortality in patients with ARDS, but such a benefit is unlikely in patients with less severe lung injuries, and could actually be harmful.

Citation: Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865-873. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

High-Performing State Healthcare Systems Have Higher Children’s Hospital Readmission Rates

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What is the relationship between a hospital’s readmission rate and performance of the surrounding healthcare system?

Background: Hospital readmission rates might be influenced by factors related to the specific patient and hospital care, as well as such external factors as the performance of the surrounding healthcare system. Traditionally, readmission rates are thought to most accurately reflect the quality of hospital care; however, the relative contributions of patient, hospital, and external factors to hospital readmission rates have not been delineated.

Study design: Multilevel cohort study.

Setting: Thirty-nine children’s hospitals in 24 states.

Synopsis: The Pediatric Health Information System (PHIS) administrative database was sampled for the 2005 calendar year to review discharges from 39 participating children’s hospitals. Patients 2 to 18 years were included, and out of a total of 198,422 patients, 32,196 were readmitted within 365 days of discharge.

The Commonwealth Fund’s 2008 State Variations in Child Health System Performance ranking was used to define the state-level health system performance. Higher readmission rates correlated with higher-ranked state child health systems after adjustment for patient-level characteristics.

This surprising result calls into question the often-assumed link between hospital readmission rates and poor systems of care. However, despite the strength of its large sample size, this study’s macro-level view of the healthcare system might be too crude to truly define the external factors that play a role in readmission. State-level healthcare rankings might not accurately reflect the healthcare ecosystem surrounding each children’s hospital, and children’s hospitals do not care for the majority of children in the U.S.

Bottom line: Children’s hospital readmissions correlate with higher state child health system performance.

Citation: Feudtner C, Pati S, Goodman DM, et al. State-level child health system performance and the likelihood of readmission to children’s hospitals. J Pediatr. 2010;157(1):98-102.