Department OF

Clinical Question: Is chest-compression-only bystander cardiopulmonary resuscitation (CPR) as effective as conventional CPR with rescue breathing for out-of-hospital cardiac arrest?

Background: Out-of-hospital cardiac arrest is a major public health problem, affecting approximately 300,000 people in the U.S. annually. Overall survival is generally less than 10% among those in whom resuscitation is attempted. Bystander CPR significantly improves outcomes but generally is performed in less than 30% of cases.

Study design: Prospective, observational cohort study.

Setting: Communities throughout the state of Arizona.

Synopsis: State officials undertook a multifaceted public service campaign to educate, inform, and encourage the use of compression-only CPR.

Over a period of four years, 5,272 adult out-of-hospital cardiac arrests were documented in Arizona. A total of 4,415 of these incidents met all of the inclusion criteria for analysis; 2,900 received no CPR, 666 received conventional CPR, and 849 received compression-only CPR. Rates of survival to hospital discharge were 5.2% for the no-CPR group, 7.8% for conventional CPR, and 13.3% for compression-only CPR.

Additionally, the successful public service campaign increased the use of lay rescuer conventional CPR by 10% and compression-only CPR by 56%.

Bottom line: Layperson, compression-only CPR was associated with an overall 6.1% increased survival compared with conventional CPR and no bystander CPR.

Citation: Bobrow BJ, Spaite DW, Berg RA, et al. Chest-compression-only CPR by lay rescuers and survival from out-of-hospital cardiac arrest. JAMA. 2010;304(13):1447-1454.

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

Clinical Question: Is chest-compression-only bystander cardiopulmonary resuscitation (CPR) as effective as conventional CPR with rescue breathing for out-of-hospital cardiac arrest?

Background: Out-of-hospital cardiac arrest is a major public health problem, affecting approximately 300,000 people in the U.S. annually. Overall survival is generally less than 10% among those in whom resuscitation is attempted. Bystander CPR significantly improves outcomes but generally is performed in less than 30% of cases.

Study design: Prospective, observational cohort study.

Setting: Communities throughout the state of Arizona.

Synopsis: State officials undertook a multifaceted public service campaign to educate, inform, and encourage the use of compression-only CPR.

Over a period of four years, 5,272 adult out-of-hospital cardiac arrests were documented in Arizona. A total of 4,415 of these incidents met all of the inclusion criteria for analysis; 2,900 received no CPR, 666 received conventional CPR, and 849 received compression-only CPR. Rates of survival to hospital discharge were 5.2% for the no-CPR group, 7.8% for conventional CPR, and 13.3% for compression-only CPR.

Additionally, the successful public service campaign increased the use of lay rescuer conventional CPR by 10% and compression-only CPR by 56%.

Bottom line: Layperson, compression-only CPR was associated with an overall 6.1% increased survival compared with conventional CPR and no bystander CPR.

Citation: Bobrow BJ, Spaite DW, Berg RA, et al. Chest-compression-only CPR by lay rescuers and survival from out-of-hospital cardiac arrest. JAMA. 2010;304(13):1447-1454.

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

Clinical Question: Is chest-compression-only bystander cardiopulmonary resuscitation (CPR) as effective as conventional CPR with rescue breathing for out-of-hospital cardiac arrest?

Background: Out-of-hospital cardiac arrest is a major public health problem, affecting approximately 300,000 people in the U.S. annually. Overall survival is generally less than 10% among those in whom resuscitation is attempted. Bystander CPR significantly improves outcomes but generally is performed in less than 30% of cases.

Study design: Prospective, observational cohort study.

Setting: Communities throughout the state of Arizona.

Synopsis: State officials undertook a multifaceted public service campaign to educate, inform, and encourage the use of compression-only CPR.

Over a period of four years, 5,272 adult out-of-hospital cardiac arrests were documented in Arizona. A total of 4,415 of these incidents met all of the inclusion criteria for analysis; 2,900 received no CPR, 666 received conventional CPR, and 849 received compression-only CPR. Rates of survival to hospital discharge were 5.2% for the no-CPR group, 7.8% for conventional CPR, and 13.3% for compression-only CPR.

Additionally, the successful public service campaign increased the use of lay rescuer conventional CPR by 10% and compression-only CPR by 56%.

Bottom line: Layperson, compression-only CPR was associated with an overall 6.1% increased survival compared with conventional CPR and no bystander CPR.

Citation: Bobrow BJ, Spaite DW, Berg RA, et al. Chest-compression-only CPR by lay rescuers and survival from out-of-hospital cardiac arrest. JAMA. 2010;304(13):1447-1454.

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

• Risk of adverse events with opioid use
• Drug of choice for outpatient treatment of cellulitis
• Preventing hospital falls
• Post-hospital outcomes based on status of PCP follow-up
• LOS, mortality, and readmission based on insurance
• Antiplatelets added to warfarin for atrial fibrillation.
• Cognitive effects of severe sepsis
• Effect of preoperative furosemide use

ED Visits Are Higher among Recipients of Chronic Opioid Therapy

Clinical question: Is there an association between the use of prescription opioids and adverse outcomes?

Background: Chronic opioid therapy is a common strategy for managing chronic, noncancer pain. There has been an increase in overdose deaths and ED visits (EDV) involving the use of prescription opioids.

Study design: Retrospective study from claims records.

Setting: Population in the Health Core Integrated Research Database, containing large, commercial insurance plans in 14 states, and Arkansas Medicaid.

Synopsis: Patients 18 and older without cancer diagnoses who used prescription opioids for at least 90 continuous days within a six-month period from 2000 to 2005 were examined for risk factors for EDVs and alcohol- or drug-related encounters (ADEs) in the 12 months following 90 days or more of prescribed opioids.

Patients with diagnoses of headache, back pain, and pre-existing substance-use disorders had significantly higher EDVs and ADEs. Opioid dose at morphine-equivalent doses over 120 mg per day doubled the risk of ADEs. The use of short-acting Schedule II opioids was associated with EDVs (relative risk, 1.09-1.74). The use of long-acting Schedule II opioids was strongly associated with ADEs (relative risk, 1.64-4.00).

Bottom line: In adults with noncancer pain prescribed opioids for 90 days or more, short-acting Schedule II opioid use was associated with an increased number of EDVs, and long-acting opioid use was associated with an increased number of ADEs. Minimizing Schedule II opioid prescription in these higher-risk patients might be prudent to increase patient safety.

Citation: Braden JB, Russo J, Fan MI, et al. Emergency department visits among recipients of chronic opioid therapy. Arch Intern Med. 2010; 170(16):1425-1432.

Empiric Outpatient Therapy with Trimethoprim-Sulfamethoxazole or Clindamycin Is Preferred for Cellulitis

Clinical question: What is the best empiric outpatient oral antibiotic treatment for cellulitis in areas with a high prevalence of community-associated MRSA infections?

Background: The increasing rates of community-associated MRSA skin and soft-tissue infections have raised concerns that such beta-lactams as cephalexin and other semisynthetic penicillins are not appropriate for empiric outpatient therapy for cellulitis.

Study design: Three-year, retrospective cohort study.

Setting: A teaching clinic of a tertiary-care medical center in Hawaii.

Synopsis: More than 540 patients with cellulitis were identified from January 2005 to December 2007. Of these, 139 patients were excluded for reasons such as hospitalization, surgical intervention, etc. In the final cohort of 405 patients, the three most commonly prescribed oral antibiotics were cephalexin (44%), trimethoprim-sulfamethoxazole (38%), and clindamycin (10%). Other antibiotics accounted for the remaining 8%.

MRSA was recovered in 62% of positive culture specimens. The success rate of trimethoprim-sulfamethoxazole was 91% vs. 74% in the cephalexin group (P<0.001). Clindamycin success rates were higher than those of cephalexin in patients who had subsequently confirmed MRSA infections (P=0.01) and moderately severe cellulitis (P=0.03) and were obese (P=0.04).

Bottom line: Antibiotics with activity against community-acquired MRSA (e.g. trimethroprim-sulfamethoxazole and clinidamycin) are the preferred empiric outpatient therapy for cellulitis in areas with a high prevalence of community-acquired MRSA.

Citation: Khawcharoenporn T, Tice A. Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis. Am J Med. 2010;123(10):942-950.

Patient-Specific Screening with Health Information Technology Prevents Falls

Clinical question: Does a fall-prevention toolkit using health information technology decrease patient falls in acute-care hospitals?

Background: Inpatient falls and fall-related injuries result in substantial morbidity and additional healthcare costs. While specific fall-prevention strategies were a longstanding target for intervention, little evidence exists to link them with decreased fall rates.

Study design: Cluster-randomized study.

Setting: Four urban hospitals in Massachusetts.

Synopsis: Comparing patient fall rates in four acute-care hospitals between units providing usual care (5,104 patients) and units using a health information technology (HIT)-linked fall prevention toolkit (5,160 patients), this study demonstrated significant fall reduction in older inpatients. The intervention integrated existing workflow and validated fall risk assessment (Morse Falls Scale) into an HIT software application that tailored fall-prevention interventions to patients’ specific fall risk determinants. The toolkit produced bed posters, patient education handouts, and plans of care communicating patient-specific alerts to key stakeholders.

The primary outcome was patient falls per 1,000 patient-days during the six-month intervention period. The number of patients with falls was significantly different (P=0.02) between control (n=87) and intervention (n=67) units. The toolkit prevented one fall per 862 patient-days.

This nonblinded study was limited by the fact that it was conducted in a single health system. The toolkit was not effective in patients less than 65 years of age. Additionally, the sample size did not have sufficient power to detect effectiveness in preventing repeat falls or falls with injury.

Bottom line: Patient-specific fall prevention strategy coupled with HIT reduces falls in older inpatients.

Citation: Dykes PC, Carroll DL, Hurley A, et al. Fall prevention in acute care hospitals: a randomized trial. JAMA. 2010;304(17):1912-1918.

Lack of Timely Outpatient Follow-Up Results in Higher Readmission Rates

Clinical question: Does timely primary-care-physician (PCP) follow-up improve outcomes and prevent hospital readmissions?

Background: Active PCP involvement is key to interventions aimed at reducing readmissions and ensuring effective ongoing patient care. Some studies suggest increased overall resource utilization when PCP follow-up occurs after hospitalization. Resource utilization and clinical outcomes after hospitalization related to timely PCP follow-up have not been adequately studied.

Study design: Prospective cohort.

Setting: An urban, academic, 425-bed tertiary-care center in Colorado.

Synopsis: From a convenience sample of 121 patients admitted to general medicine services during winter months, 65 patients completed the study. Demographics, diagnosis, payor source, and PCP information were collected upon enrollment. Post-discharge phone calls and patient surveys were used to determine follow-up and readmission status. Timely PCP follow-up was defined as a visit with a PCP or specialist related to the discharge diagnosis within four weeks of hospital discharge.

Thirty-day readmission rates and hospital length of stay were compared for those with timely PCP follow-up and those without. Less than half of general-medicine inpatients received timely PCP follow-up post-discharge. Lack of timely PCP follow-up was associated with younger age, a 10-fold increase in 30-day readmission for the same condition, and a trend toward longer length of stay. However, hospital readmission for any condition did not differ with lack of timely PCP follow-up.

This small, single-center study with convenience sample enrollment might not represent all medical inpatients or diagnoses. Determination of same-condition readmission was potentially subjective.

Bottom line: Patients who lack timely post-discharge follow-up have higher readmission rates for the same medical condition.

Citation: Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397.

Compared with Uninsured and Medicaid Patients, Privately Insured Patients Admitted for Acute MI, Stroke, and Pneumonia Have Better Mortality Rates

Clinical question: Do outcomes for insured and underinsured patients vary for three of the most common medical conditions for which patients are hospitalized: acute myocardial infarction (AMI), stroke, and pneumonia?

Background: The ideal healthcare system would provide quality care to all individuals regardless of insurance status. Nevertheless, disparities in outcomes for the insured and underinsured or uninsured are well-documented in the outpatient setting but not as well in the inpatient setting. More needs to be done to address these potential disparities.

Study design: Retrospective database analysis.

Setting: Database including 20% of all U.S. community hospitals, including public hospitals, academic medical centers, and specialty hospitals.

Synopsis: This study utilized a database of 8 million discharges from more than 1,000 hospitals and isolated patients 18-64 years old (154,381 patients). Privately insured, uninsured, and Medicaid patients’ data were reviewed for in-hospital mortality, length of stay (LOS), and cost per hospitalization. The analysis took into account disease severity, comorbidities, and the proportion of underinsured patients receiving care in each hospital when insurance-related disparities were examined.

Compared with the privately insured, in-hospital mortality and LOS for AMI and stroke were significantly higher for uninsured and Medicaid patients. Among pneumonia patients, Medicaid patients had significantly higher in-hospital mortality and LOS than the other two groups. Cost per hospitalization was highest for all three conditions in the Medicaid group; the uninsured group had the lowest costs for all three conditions.

Unfortunately, the three conditions analyzed only comprise 8% of annual hospital discharges, so the findings cannot be generalized. Also, deaths occurring soon after hospital discharge were not included, and uninsured and Medicaid patients are likely to have more severe diseases, which, rather than insurance status, could account for the mortality differences.

Bottom line: In-hospital mortality and resource use for three common medical conditions vary significantly between privately insured and uninsured or Medicaid patients, highlighting the need to take measures to close this gap.

Citation: Hasan O, Orav EJ, LeRoi LS. Insurance status and hospital care for myocardial infarction, stroke, and pneumonia. J Hosp Med. 2010;5(8);452-459.

Warfarin Monotherapy Best in Prevention of Thromboembolic Events for Atrial Fibrillation Patients

Clinical question: Is there a benefit to adding an antiplatelet agent to warfarin for the prevention of thromboembolic stroke in atrial fibrillation?

Background: Many physicians prescribe various combinations of aspirin, clopidogrel, and warfarin, as these treatments are endorsed in guidelines and expert statements. The use of these medications, however, has not been studied in a setting large enough to understand the safety of these therapies.

Study design: Retrospective cohort.

Setting: All Danish hospitals.

Synopsis: All hospitalized patients in Denmark from 1997 to 2006 who were identified with new onset atrial fibrillation (n=118,606) were monitored for outcomes and the use of aspirin, clopidogrel, and warfarin. These patients were followed for a mean of 3.3 years with the primary endpoint being admission to a hospital for a diagnosis of bleeding and a secondary endpoint of stroke.

Bleeding occurred in 13,573 patients (11.4%). The incidence of bleeding was highest in the first 180 days and then leveled off. Hazard ratios were computed with warfarin monotherapy as a reference. Only the hazard ratio for aspirin monotherapy (0.93) was lower (confidence interval [CI] 0.88-0.98). The highest risk of bleeding was with the triple therapy warfarin-aspirin-clopidogrel, which had a hazard ratio of 3.70 (CI 2.89-4.76).

For strokes, the hazard ratio was slightly better for warfarin-clopidogrel (0.70), although the CI was wide at 0.35-1.4 compared to warfarin monotherapy as a reference. Hazard ratios for monotherapy with clopidogrel or aspirin, dual therapy, and triple therapy all were worse, ranging from 1.27 to 1.86.

Bottom line: Warfarin as a monotherapy might have a bleeding risk comparable to that of aspirin or clopidogrel alone, and prevents more strokes than various combinations of these medications.

Citation: Hansen ML, Sørensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170 (16):1433-1441.

Cognitive and Physical Function Declines in Elderly Severe Sepsis Survivors

Clinical question: Is there a change in cognitive and physical functioning after severe sepsis?

Background: Disability is associated with increased mortality, decreased quality of life, and increased burdens by families and healthcare costs. After severe sepsis, the lasting effects of debility have not been investigated in any large studies.

Study design: Prospective cohort.

Setting: Hospitalized Medicare patients participating in the Health and Retirement Study.

Synopsis: Patients (n=1194) were followed for a minimum of one year between 1998 and 2006. The outcomes were measured by multiple personal interviews before and after a severe sepsis episode. Cognitive impairment was measured using three validated questionnaires dependent upon age or if a proxy was the respondent. For functional limitations, a questionnaire concerning instrumental and basic activities of daily living was used.

Cognitive impairment for those with moderate to severe impairment increased to 16.7% from 6.1% after a sepsis episode with an odds ratio of 3.34 (95% confidence interval 1.53-7.25). There was no significant increase in nonsevere sepsis hospitalized comparison patients (n=5574). All survivors with severe sepsis had a functional decline of 1.5 activities. The comparison group had about a 0.4 activity decline. All of these deficits endured throughout the study.

The authors provide comments that there should be a system-based approach in preventing severe sepsis, its burdens, and its costs. Suggestions include preventing delirium, initiating better standards of care, and involving therapists earlier to prevent immobility.

Bottom line: Severe sepsis is independently associated with enduring cognitive and physical functional declines, which strain families and our healthcare system.

Citation: Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-1794.

Furosemide on Day of Elective Noncardiac Surgery Does Not Increase Risk of Intraoperative Hypotension

Clinical question: For patients chronically treated with loop diuretics, does withholding furosemide on the day of elective noncardiac surgery prevent intraoperative hypotension?

Background: Recent studies have questioned the safety of blood-pressure-lowering medications administered on the day of surgery. Beta-blockers have been associated with an increase in strokes and death perioperatively, and angiotensin receptor blockers (ARB) are frequently withheld on the day of surgery to avoid intraoperative hypotension. The effect of loop diuretics is uncertain.

Study design: Double-blind, randomized, placebo-controlled study.

Setting: Three North American university centers.

Synopsis: One hundred ninety-three patients were instructed to take furosemide or placebo on the day they underwent noncardiac surgery. The primary outcome measure was perioperative hypotension defined as a SBP <90 mmHg for more than five minutes, a 35% drop in the mean arterial blood pressure, or the need for a vasopressor agent. The number of cardiovascular complications (acute heart failure, acute coronary syndrome, arrhythmia, acute cerebrovascular event) and deaths also were analyzed.

Concerns have been raised that loop diuretics might predispose patients to a higher risk of intraoperative hypotension during noncardiac surgery. This trial showed no significant difference in the rates of intraoperative hypotension in patients who were administered furosemide versus those who were not. Although cardiovascular complications occurred more frequently in the furosemide group, the difference was not statistically significant.

Important limitations of the study were recognized. A larger population of patients could have revealed a statistically significant difference in cardiovascular outcomes in the furosemide group. Also, an anesthetic protocol was not utilized, which raises questions about the interaction of furosemide and effect on blood pressure with certain anesthetics.

Bottom line: Administering furosemide prior to surgery in chronic users does not appreciably increase the rate of intraoperative hypotension or cardiovascular events.

Citation: Khan NA, Campbell NR, Frost SD, et al. Risk of intraoperative hypotension with loop diuretics: a randomized controlled trial. Am J Med. 2010;123(11):1059e1-1059e8.

Pediatric HM Literature

Computerized Physician Order Entry Decreases Hospitalwide Mortality

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 effect of computerized physician order entry (CPOE) on hospitalwide mortality?

Background: CPOE has been touted as a key method for improving the quality and safety of patient care. To date, however, studies have not demonstrated definitive benefits, with one study demonstrating an increase in mortality rates in a critical-care unit after CPOE implementation.

Study design: Retrospective cohort study.

Setting: Quaternary-care academic children’s hospital.

Synopsis: More than 97,000 nonobstetric patients admitted to Lucile Packard Children’s Hospital (LCPH) at Stanford University in Palo Alto, Calif., from January 2001 to April 2009 were included in the analysis. The patients were divided into pre- and postintervention groups. The intervention was defined as a “big bang” activation of CPOE on Nov. 4, 2007, affecting 90% of the inpatient beds at LCPH.

After the intervention, mean monthly unadjusted mortality rates decreased to 0.716 deaths from 1.008 per 100 discharges. After adjustment for severity of illness and a rapid-response team (which had previously been shown to decrease mortality rates), mortality rates postintervention continued to remain significantly lower.

This study revealed an impressive reduction in perhaps the ultimate outcome measure: hospitalwide mortality. The authors went to extensive lengths to adjust for potential confounding factors to include delayed implementation of CPOE in the ICUs. As with many complex process improvement efforts, the devil might be in the details of local context and culture. Thus, the software might have been less important than the manner in which the institution adapted to its functionality. Those seeking to replicate these results will need to be mindful of the requisite organizational changes in communication, order standardization, and data retrieval.

Bottom line: CPOE implementation has the potential to significantly reduce hospitalwide mortality rates.

Citation: Longhurst CA, Parast L, Sandborg CI, et al. Decrease in hospital-wide mortality rate after implementation of a commercially sold computerized physician order entry system. Pediatrics. 2010;126(1):e1-e8.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Risk of adverse events with opioid use
• Drug of choice for outpatient treatment of cellulitis
• Preventing hospital falls
• Post-hospital outcomes based on status of PCP follow-up
• LOS, mortality, and readmission based on insurance
• Antiplatelets added to warfarin for atrial fibrillation.
• Cognitive effects of severe sepsis
• Effect of preoperative furosemide use

ED Visits Are Higher among Recipients of Chronic Opioid Therapy

Clinical question: Is there an association between the use of prescription opioids and adverse outcomes?

Background: Chronic opioid therapy is a common strategy for managing chronic, noncancer pain. There has been an increase in overdose deaths and ED visits (EDV) involving the use of prescription opioids.

Study design: Retrospective study from claims records.

Setting: Population in the Health Core Integrated Research Database, containing large, commercial insurance plans in 14 states, and Arkansas Medicaid.

Synopsis: Patients 18 and older without cancer diagnoses who used prescription opioids for at least 90 continuous days within a six-month period from 2000 to 2005 were examined for risk factors for EDVs and alcohol- or drug-related encounters (ADEs) in the 12 months following 90 days or more of prescribed opioids.

Patients with diagnoses of headache, back pain, and pre-existing substance-use disorders had significantly higher EDVs and ADEs. Opioid dose at morphine-equivalent doses over 120 mg per day doubled the risk of ADEs. The use of short-acting Schedule II opioids was associated with EDVs (relative risk, 1.09-1.74). The use of long-acting Schedule II opioids was strongly associated with ADEs (relative risk, 1.64-4.00).

Bottom line: In adults with noncancer pain prescribed opioids for 90 days or more, short-acting Schedule II opioid use was associated with an increased number of EDVs, and long-acting opioid use was associated with an increased number of ADEs. Minimizing Schedule II opioid prescription in these higher-risk patients might be prudent to increase patient safety.

Citation: Braden JB, Russo J, Fan MI, et al. Emergency department visits among recipients of chronic opioid therapy. Arch Intern Med. 2010; 170(16):1425-1432.

Empiric Outpatient Therapy with Trimethoprim-Sulfamethoxazole or Clindamycin Is Preferred for Cellulitis

Clinical question: What is the best empiric outpatient oral antibiotic treatment for cellulitis in areas with a high prevalence of community-associated MRSA infections?

Background: The increasing rates of community-associated MRSA skin and soft-tissue infections have raised concerns that such beta-lactams as cephalexin and other semisynthetic penicillins are not appropriate for empiric outpatient therapy for cellulitis.

Study design: Three-year, retrospective cohort study.

Setting: A teaching clinic of a tertiary-care medical center in Hawaii.

Synopsis: More than 540 patients with cellulitis were identified from January 2005 to December 2007. Of these, 139 patients were excluded for reasons such as hospitalization, surgical intervention, etc. In the final cohort of 405 patients, the three most commonly prescribed oral antibiotics were cephalexin (44%), trimethoprim-sulfamethoxazole (38%), and clindamycin (10%). Other antibiotics accounted for the remaining 8%.

MRSA was recovered in 62% of positive culture specimens. The success rate of trimethoprim-sulfamethoxazole was 91% vs. 74% in the cephalexin group (P<0.001). Clindamycin success rates were higher than those of cephalexin in patients who had subsequently confirmed MRSA infections (P=0.01) and moderately severe cellulitis (P=0.03) and were obese (P=0.04).

Bottom line: Antibiotics with activity against community-acquired MRSA (e.g. trimethroprim-sulfamethoxazole and clinidamycin) are the preferred empiric outpatient therapy for cellulitis in areas with a high prevalence of community-acquired MRSA.

Citation: Khawcharoenporn T, Tice A. Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis. Am J Med. 2010;123(10):942-950.

Patient-Specific Screening with Health Information Technology Prevents Falls

Clinical question: Does a fall-prevention toolkit using health information technology decrease patient falls in acute-care hospitals?

Background: Inpatient falls and fall-related injuries result in substantial morbidity and additional healthcare costs. While specific fall-prevention strategies were a longstanding target for intervention, little evidence exists to link them with decreased fall rates.

Study design: Cluster-randomized study.

Setting: Four urban hospitals in Massachusetts.

Synopsis: Comparing patient fall rates in four acute-care hospitals between units providing usual care (5,104 patients) and units using a health information technology (HIT)-linked fall prevention toolkit (5,160 patients), this study demonstrated significant fall reduction in older inpatients. The intervention integrated existing workflow and validated fall risk assessment (Morse Falls Scale) into an HIT software application that tailored fall-prevention interventions to patients’ specific fall risk determinants. The toolkit produced bed posters, patient education handouts, and plans of care communicating patient-specific alerts to key stakeholders.

The primary outcome was patient falls per 1,000 patient-days during the six-month intervention period. The number of patients with falls was significantly different (P=0.02) between control (n=87) and intervention (n=67) units. The toolkit prevented one fall per 862 patient-days.

This nonblinded study was limited by the fact that it was conducted in a single health system. The toolkit was not effective in patients less than 65 years of age. Additionally, the sample size did not have sufficient power to detect effectiveness in preventing repeat falls or falls with injury.

Bottom line: Patient-specific fall prevention strategy coupled with HIT reduces falls in older inpatients.

Citation: Dykes PC, Carroll DL, Hurley A, et al. Fall prevention in acute care hospitals: a randomized trial. JAMA. 2010;304(17):1912-1918.

Lack of Timely Outpatient Follow-Up Results in Higher Readmission Rates

Clinical question: Does timely primary-care-physician (PCP) follow-up improve outcomes and prevent hospital readmissions?

Background: Active PCP involvement is key to interventions aimed at reducing readmissions and ensuring effective ongoing patient care. Some studies suggest increased overall resource utilization when PCP follow-up occurs after hospitalization. Resource utilization and clinical outcomes after hospitalization related to timely PCP follow-up have not been adequately studied.

Study design: Prospective cohort.

Setting: An urban, academic, 425-bed tertiary-care center in Colorado.

Synopsis: From a convenience sample of 121 patients admitted to general medicine services during winter months, 65 patients completed the study. Demographics, diagnosis, payor source, and PCP information were collected upon enrollment. Post-discharge phone calls and patient surveys were used to determine follow-up and readmission status. Timely PCP follow-up was defined as a visit with a PCP or specialist related to the discharge diagnosis within four weeks of hospital discharge.

Thirty-day readmission rates and hospital length of stay were compared for those with timely PCP follow-up and those without. Less than half of general-medicine inpatients received timely PCP follow-up post-discharge. Lack of timely PCP follow-up was associated with younger age, a 10-fold increase in 30-day readmission for the same condition, and a trend toward longer length of stay. However, hospital readmission for any condition did not differ with lack of timely PCP follow-up.

This small, single-center study with convenience sample enrollment might not represent all medical inpatients or diagnoses. Determination of same-condition readmission was potentially subjective.

Bottom line: Patients who lack timely post-discharge follow-up have higher readmission rates for the same medical condition.

Citation: Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397.

Compared with Uninsured and Medicaid Patients, Privately Insured Patients Admitted for Acute MI, Stroke, and Pneumonia Have Better Mortality Rates

Clinical question: Do outcomes for insured and underinsured patients vary for three of the most common medical conditions for which patients are hospitalized: acute myocardial infarction (AMI), stroke, and pneumonia?

Background: The ideal healthcare system would provide quality care to all individuals regardless of insurance status. Nevertheless, disparities in outcomes for the insured and underinsured or uninsured are well-documented in the outpatient setting but not as well in the inpatient setting. More needs to be done to address these potential disparities.

Study design: Retrospective database analysis.

Setting: Database including 20% of all U.S. community hospitals, including public hospitals, academic medical centers, and specialty hospitals.

Synopsis: This study utilized a database of 8 million discharges from more than 1,000 hospitals and isolated patients 18-64 years old (154,381 patients). Privately insured, uninsured, and Medicaid patients’ data were reviewed for in-hospital mortality, length of stay (LOS), and cost per hospitalization. The analysis took into account disease severity, comorbidities, and the proportion of underinsured patients receiving care in each hospital when insurance-related disparities were examined.

Compared with the privately insured, in-hospital mortality and LOS for AMI and stroke were significantly higher for uninsured and Medicaid patients. Among pneumonia patients, Medicaid patients had significantly higher in-hospital mortality and LOS than the other two groups. Cost per hospitalization was highest for all three conditions in the Medicaid group; the uninsured group had the lowest costs for all three conditions.

Unfortunately, the three conditions analyzed only comprise 8% of annual hospital discharges, so the findings cannot be generalized. Also, deaths occurring soon after hospital discharge were not included, and uninsured and Medicaid patients are likely to have more severe diseases, which, rather than insurance status, could account for the mortality differences.

Bottom line: In-hospital mortality and resource use for three common medical conditions vary significantly between privately insured and uninsured or Medicaid patients, highlighting the need to take measures to close this gap.

Citation: Hasan O, Orav EJ, LeRoi LS. Insurance status and hospital care for myocardial infarction, stroke, and pneumonia. J Hosp Med. 2010;5(8);452-459.

Warfarin Monotherapy Best in Prevention of Thromboembolic Events for Atrial Fibrillation Patients

Clinical question: Is there a benefit to adding an antiplatelet agent to warfarin for the prevention of thromboembolic stroke in atrial fibrillation?

Background: Many physicians prescribe various combinations of aspirin, clopidogrel, and warfarin, as these treatments are endorsed in guidelines and expert statements. The use of these medications, however, has not been studied in a setting large enough to understand the safety of these therapies.

Study design: Retrospective cohort.

Setting: All Danish hospitals.

Synopsis: All hospitalized patients in Denmark from 1997 to 2006 who were identified with new onset atrial fibrillation (n=118,606) were monitored for outcomes and the use of aspirin, clopidogrel, and warfarin. These patients were followed for a mean of 3.3 years with the primary endpoint being admission to a hospital for a diagnosis of bleeding and a secondary endpoint of stroke.

Bleeding occurred in 13,573 patients (11.4%). The incidence of bleeding was highest in the first 180 days and then leveled off. Hazard ratios were computed with warfarin monotherapy as a reference. Only the hazard ratio for aspirin monotherapy (0.93) was lower (confidence interval [CI] 0.88-0.98). The highest risk of bleeding was with the triple therapy warfarin-aspirin-clopidogrel, which had a hazard ratio of 3.70 (CI 2.89-4.76).

For strokes, the hazard ratio was slightly better for warfarin-clopidogrel (0.70), although the CI was wide at 0.35-1.4 compared to warfarin monotherapy as a reference. Hazard ratios for monotherapy with clopidogrel or aspirin, dual therapy, and triple therapy all were worse, ranging from 1.27 to 1.86.

Bottom line: Warfarin as a monotherapy might have a bleeding risk comparable to that of aspirin or clopidogrel alone, and prevents more strokes than various combinations of these medications.

Citation: Hansen ML, Sørensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170 (16):1433-1441.

Cognitive and Physical Function Declines in Elderly Severe Sepsis Survivors

Clinical question: Is there a change in cognitive and physical functioning after severe sepsis?

Background: Disability is associated with increased mortality, decreased quality of life, and increased burdens by families and healthcare costs. After severe sepsis, the lasting effects of debility have not been investigated in any large studies.

Study design: Prospective cohort.

Setting: Hospitalized Medicare patients participating in the Health and Retirement Study.

Synopsis: Patients (n=1194) were followed for a minimum of one year between 1998 and 2006. The outcomes were measured by multiple personal interviews before and after a severe sepsis episode. Cognitive impairment was measured using three validated questionnaires dependent upon age or if a proxy was the respondent. For functional limitations, a questionnaire concerning instrumental and basic activities of daily living was used.

Cognitive impairment for those with moderate to severe impairment increased to 16.7% from 6.1% after a sepsis episode with an odds ratio of 3.34 (95% confidence interval 1.53-7.25). There was no significant increase in nonsevere sepsis hospitalized comparison patients (n=5574). All survivors with severe sepsis had a functional decline of 1.5 activities. The comparison group had about a 0.4 activity decline. All of these deficits endured throughout the study.

The authors provide comments that there should be a system-based approach in preventing severe sepsis, its burdens, and its costs. Suggestions include preventing delirium, initiating better standards of care, and involving therapists earlier to prevent immobility.

Bottom line: Severe sepsis is independently associated with enduring cognitive and physical functional declines, which strain families and our healthcare system.

Citation: Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-1794.

Furosemide on Day of Elective Noncardiac Surgery Does Not Increase Risk of Intraoperative Hypotension

Clinical question: For patients chronically treated with loop diuretics, does withholding furosemide on the day of elective noncardiac surgery prevent intraoperative hypotension?

Background: Recent studies have questioned the safety of blood-pressure-lowering medications administered on the day of surgery. Beta-blockers have been associated with an increase in strokes and death perioperatively, and angiotensin receptor blockers (ARB) are frequently withheld on the day of surgery to avoid intraoperative hypotension. The effect of loop diuretics is uncertain.

Study design: Double-blind, randomized, placebo-controlled study.

Setting: Three North American university centers.

Synopsis: One hundred ninety-three patients were instructed to take furosemide or placebo on the day they underwent noncardiac surgery. The primary outcome measure was perioperative hypotension defined as a SBP <90 mmHg for more than five minutes, a 35% drop in the mean arterial blood pressure, or the need for a vasopressor agent. The number of cardiovascular complications (acute heart failure, acute coronary syndrome, arrhythmia, acute cerebrovascular event) and deaths also were analyzed.

Concerns have been raised that loop diuretics might predispose patients to a higher risk of intraoperative hypotension during noncardiac surgery. This trial showed no significant difference in the rates of intraoperative hypotension in patients who were administered furosemide versus those who were not. Although cardiovascular complications occurred more frequently in the furosemide group, the difference was not statistically significant.

Important limitations of the study were recognized. A larger population of patients could have revealed a statistically significant difference in cardiovascular outcomes in the furosemide group. Also, an anesthetic protocol was not utilized, which raises questions about the interaction of furosemide and effect on blood pressure with certain anesthetics.

Bottom line: Administering furosemide prior to surgery in chronic users does not appreciably increase the rate of intraoperative hypotension or cardiovascular events.

Citation: Khan NA, Campbell NR, Frost SD, et al. Risk of intraoperative hypotension with loop diuretics: a randomized controlled trial. Am J Med. 2010;123(11):1059e1-1059e8.

Pediatric HM Literature

Computerized Physician Order Entry Decreases Hospitalwide Mortality

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 effect of computerized physician order entry (CPOE) on hospitalwide mortality?

Background: CPOE has been touted as a key method for improving the quality and safety of patient care. To date, however, studies have not demonstrated definitive benefits, with one study demonstrating an increase in mortality rates in a critical-care unit after CPOE implementation.

Study design: Retrospective cohort study.

Setting: Quaternary-care academic children’s hospital.

Synopsis: More than 97,000 nonobstetric patients admitted to Lucile Packard Children’s Hospital (LCPH) at Stanford University in Palo Alto, Calif., from January 2001 to April 2009 were included in the analysis. The patients were divided into pre- and postintervention groups. The intervention was defined as a “big bang” activation of CPOE on Nov. 4, 2007, affecting 90% of the inpatient beds at LCPH.

After the intervention, mean monthly unadjusted mortality rates decreased to 0.716 deaths from 1.008 per 100 discharges. After adjustment for severity of illness and a rapid-response team (which had previously been shown to decrease mortality rates), mortality rates postintervention continued to remain significantly lower.

This study revealed an impressive reduction in perhaps the ultimate outcome measure: hospitalwide mortality. The authors went to extensive lengths to adjust for potential confounding factors to include delayed implementation of CPOE in the ICUs. As with many complex process improvement efforts, the devil might be in the details of local context and culture. Thus, the software might have been less important than the manner in which the institution adapted to its functionality. Those seeking to replicate these results will need to be mindful of the requisite organizational changes in communication, order standardization, and data retrieval.

Bottom line: CPOE implementation has the potential to significantly reduce hospitalwide mortality rates.

Citation: Longhurst CA, Parast L, Sandborg CI, et al. Decrease in hospital-wide mortality rate after implementation of a commercially sold computerized physician order entry system. Pediatrics. 2010;126(1):e1-e8.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Risk of adverse events with opioid use
• Drug of choice for outpatient treatment of cellulitis
• Preventing hospital falls
• Post-hospital outcomes based on status of PCP follow-up
• LOS, mortality, and readmission based on insurance
• Antiplatelets added to warfarin for atrial fibrillation.
• Cognitive effects of severe sepsis
• Effect of preoperative furosemide use

ED Visits Are Higher among Recipients of Chronic Opioid Therapy

Clinical question: Is there an association between the use of prescription opioids and adverse outcomes?

Background: Chronic opioid therapy is a common strategy for managing chronic, noncancer pain. There has been an increase in overdose deaths and ED visits (EDV) involving the use of prescription opioids.

Study design: Retrospective study from claims records.

Setting: Population in the Health Core Integrated Research Database, containing large, commercial insurance plans in 14 states, and Arkansas Medicaid.

Synopsis: Patients 18 and older without cancer diagnoses who used prescription opioids for at least 90 continuous days within a six-month period from 2000 to 2005 were examined for risk factors for EDVs and alcohol- or drug-related encounters (ADEs) in the 12 months following 90 days or more of prescribed opioids.

Patients with diagnoses of headache, back pain, and pre-existing substance-use disorders had significantly higher EDVs and ADEs. Opioid dose at morphine-equivalent doses over 120 mg per day doubled the risk of ADEs. The use of short-acting Schedule II opioids was associated with EDVs (relative risk, 1.09-1.74). The use of long-acting Schedule II opioids was strongly associated with ADEs (relative risk, 1.64-4.00).

Bottom line: In adults with noncancer pain prescribed opioids for 90 days or more, short-acting Schedule II opioid use was associated with an increased number of EDVs, and long-acting opioid use was associated with an increased number of ADEs. Minimizing Schedule II opioid prescription in these higher-risk patients might be prudent to increase patient safety.

Citation: Braden JB, Russo J, Fan MI, et al. Emergency department visits among recipients of chronic opioid therapy. Arch Intern Med. 2010; 170(16):1425-1432.

Empiric Outpatient Therapy with Trimethoprim-Sulfamethoxazole or Clindamycin Is Preferred for Cellulitis

Clinical question: What is the best empiric outpatient oral antibiotic treatment for cellulitis in areas with a high prevalence of community-associated MRSA infections?

Background: The increasing rates of community-associated MRSA skin and soft-tissue infections have raised concerns that such beta-lactams as cephalexin and other semisynthetic penicillins are not appropriate for empiric outpatient therapy for cellulitis.

Study design: Three-year, retrospective cohort study.

Setting: A teaching clinic of a tertiary-care medical center in Hawaii.

Synopsis: More than 540 patients with cellulitis were identified from January 2005 to December 2007. Of these, 139 patients were excluded for reasons such as hospitalization, surgical intervention, etc. In the final cohort of 405 patients, the three most commonly prescribed oral antibiotics were cephalexin (44%), trimethoprim-sulfamethoxazole (38%), and clindamycin (10%). Other antibiotics accounted for the remaining 8%.

MRSA was recovered in 62% of positive culture specimens. The success rate of trimethoprim-sulfamethoxazole was 91% vs. 74% in the cephalexin group (P<0.001). Clindamycin success rates were higher than those of cephalexin in patients who had subsequently confirmed MRSA infections (P=0.01) and moderately severe cellulitis (P=0.03) and were obese (P=0.04).

Bottom line: Antibiotics with activity against community-acquired MRSA (e.g. trimethroprim-sulfamethoxazole and clinidamycin) are the preferred empiric outpatient therapy for cellulitis in areas with a high prevalence of community-acquired MRSA.

Citation: Khawcharoenporn T, Tice A. Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis. Am J Med. 2010;123(10):942-950.

Patient-Specific Screening with Health Information Technology Prevents Falls

Clinical question: Does a fall-prevention toolkit using health information technology decrease patient falls in acute-care hospitals?

Background: Inpatient falls and fall-related injuries result in substantial morbidity and additional healthcare costs. While specific fall-prevention strategies were a longstanding target for intervention, little evidence exists to link them with decreased fall rates.

Study design: Cluster-randomized study.

Setting: Four urban hospitals in Massachusetts.

Synopsis: Comparing patient fall rates in four acute-care hospitals between units providing usual care (5,104 patients) and units using a health information technology (HIT)-linked fall prevention toolkit (5,160 patients), this study demonstrated significant fall reduction in older inpatients. The intervention integrated existing workflow and validated fall risk assessment (Morse Falls Scale) into an HIT software application that tailored fall-prevention interventions to patients’ specific fall risk determinants. The toolkit produced bed posters, patient education handouts, and plans of care communicating patient-specific alerts to key stakeholders.

The primary outcome was patient falls per 1,000 patient-days during the six-month intervention period. The number of patients with falls was significantly different (P=0.02) between control (n=87) and intervention (n=67) units. The toolkit prevented one fall per 862 patient-days.

This nonblinded study was limited by the fact that it was conducted in a single health system. The toolkit was not effective in patients less than 65 years of age. Additionally, the sample size did not have sufficient power to detect effectiveness in preventing repeat falls or falls with injury.

Bottom line: Patient-specific fall prevention strategy coupled with HIT reduces falls in older inpatients.

Citation: Dykes PC, Carroll DL, Hurley A, et al. Fall prevention in acute care hospitals: a randomized trial. JAMA. 2010;304(17):1912-1918.

Lack of Timely Outpatient Follow-Up Results in Higher Readmission Rates

Clinical question: Does timely primary-care-physician (PCP) follow-up improve outcomes and prevent hospital readmissions?

Background: Active PCP involvement is key to interventions aimed at reducing readmissions and ensuring effective ongoing patient care. Some studies suggest increased overall resource utilization when PCP follow-up occurs after hospitalization. Resource utilization and clinical outcomes after hospitalization related to timely PCP follow-up have not been adequately studied.

Study design: Prospective cohort.

Setting: An urban, academic, 425-bed tertiary-care center in Colorado.

Synopsis: From a convenience sample of 121 patients admitted to general medicine services during winter months, 65 patients completed the study. Demographics, diagnosis, payor source, and PCP information were collected upon enrollment. Post-discharge phone calls and patient surveys were used to determine follow-up and readmission status. Timely PCP follow-up was defined as a visit with a PCP or specialist related to the discharge diagnosis within four weeks of hospital discharge.

Thirty-day readmission rates and hospital length of stay were compared for those with timely PCP follow-up and those without. Less than half of general-medicine inpatients received timely PCP follow-up post-discharge. Lack of timely PCP follow-up was associated with younger age, a 10-fold increase in 30-day readmission for the same condition, and a trend toward longer length of stay. However, hospital readmission for any condition did not differ with lack of timely PCP follow-up.

This small, single-center study with convenience sample enrollment might not represent all medical inpatients or diagnoses. Determination of same-condition readmission was potentially subjective.

Bottom line: Patients who lack timely post-discharge follow-up have higher readmission rates for the same medical condition.

Citation: Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397.

Compared with Uninsured and Medicaid Patients, Privately Insured Patients Admitted for Acute MI, Stroke, and Pneumonia Have Better Mortality Rates

Clinical question: Do outcomes for insured and underinsured patients vary for three of the most common medical conditions for which patients are hospitalized: acute myocardial infarction (AMI), stroke, and pneumonia?

Background: The ideal healthcare system would provide quality care to all individuals regardless of insurance status. Nevertheless, disparities in outcomes for the insured and underinsured or uninsured are well-documented in the outpatient setting but not as well in the inpatient setting. More needs to be done to address these potential disparities.

Study design: Retrospective database analysis.

Setting: Database including 20% of all U.S. community hospitals, including public hospitals, academic medical centers, and specialty hospitals.

Synopsis: This study utilized a database of 8 million discharges from more than 1,000 hospitals and isolated patients 18-64 years old (154,381 patients). Privately insured, uninsured, and Medicaid patients’ data were reviewed for in-hospital mortality, length of stay (LOS), and cost per hospitalization. The analysis took into account disease severity, comorbidities, and the proportion of underinsured patients receiving care in each hospital when insurance-related disparities were examined.

Compared with the privately insured, in-hospital mortality and LOS for AMI and stroke were significantly higher for uninsured and Medicaid patients. Among pneumonia patients, Medicaid patients had significantly higher in-hospital mortality and LOS than the other two groups. Cost per hospitalization was highest for all three conditions in the Medicaid group; the uninsured group had the lowest costs for all three conditions.

Unfortunately, the three conditions analyzed only comprise 8% of annual hospital discharges, so the findings cannot be generalized. Also, deaths occurring soon after hospital discharge were not included, and uninsured and Medicaid patients are likely to have more severe diseases, which, rather than insurance status, could account for the mortality differences.

Bottom line: In-hospital mortality and resource use for three common medical conditions vary significantly between privately insured and uninsured or Medicaid patients, highlighting the need to take measures to close this gap.

Citation: Hasan O, Orav EJ, LeRoi LS. Insurance status and hospital care for myocardial infarction, stroke, and pneumonia. J Hosp Med. 2010;5(8);452-459.

Warfarin Monotherapy Best in Prevention of Thromboembolic Events for Atrial Fibrillation Patients

Clinical question: Is there a benefit to adding an antiplatelet agent to warfarin for the prevention of thromboembolic stroke in atrial fibrillation?

Background: Many physicians prescribe various combinations of aspirin, clopidogrel, and warfarin, as these treatments are endorsed in guidelines and expert statements. The use of these medications, however, has not been studied in a setting large enough to understand the safety of these therapies.

Study design: Retrospective cohort.

Setting: All Danish hospitals.

Synopsis: All hospitalized patients in Denmark from 1997 to 2006 who were identified with new onset atrial fibrillation (n=118,606) were monitored for outcomes and the use of aspirin, clopidogrel, and warfarin. These patients were followed for a mean of 3.3 years with the primary endpoint being admission to a hospital for a diagnosis of bleeding and a secondary endpoint of stroke.

Bleeding occurred in 13,573 patients (11.4%). The incidence of bleeding was highest in the first 180 days and then leveled off. Hazard ratios were computed with warfarin monotherapy as a reference. Only the hazard ratio for aspirin monotherapy (0.93) was lower (confidence interval [CI] 0.88-0.98). The highest risk of bleeding was with the triple therapy warfarin-aspirin-clopidogrel, which had a hazard ratio of 3.70 (CI 2.89-4.76).

For strokes, the hazard ratio was slightly better for warfarin-clopidogrel (0.70), although the CI was wide at 0.35-1.4 compared to warfarin monotherapy as a reference. Hazard ratios for monotherapy with clopidogrel or aspirin, dual therapy, and triple therapy all were worse, ranging from 1.27 to 1.86.

Bottom line: Warfarin as a monotherapy might have a bleeding risk comparable to that of aspirin or clopidogrel alone, and prevents more strokes than various combinations of these medications.

Citation: Hansen ML, Sørensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170 (16):1433-1441.

Cognitive and Physical Function Declines in Elderly Severe Sepsis Survivors

Clinical question: Is there a change in cognitive and physical functioning after severe sepsis?

Background: Disability is associated with increased mortality, decreased quality of life, and increased burdens by families and healthcare costs. After severe sepsis, the lasting effects of debility have not been investigated in any large studies.

Study design: Prospective cohort.

Setting: Hospitalized Medicare patients participating in the Health and Retirement Study.

Synopsis: Patients (n=1194) were followed for a minimum of one year between 1998 and 2006. The outcomes were measured by multiple personal interviews before and after a severe sepsis episode. Cognitive impairment was measured using three validated questionnaires dependent upon age or if a proxy was the respondent. For functional limitations, a questionnaire concerning instrumental and basic activities of daily living was used.

Cognitive impairment for those with moderate to severe impairment increased to 16.7% from 6.1% after a sepsis episode with an odds ratio of 3.34 (95% confidence interval 1.53-7.25). There was no significant increase in nonsevere sepsis hospitalized comparison patients (n=5574). All survivors with severe sepsis had a functional decline of 1.5 activities. The comparison group had about a 0.4 activity decline. All of these deficits endured throughout the study.

The authors provide comments that there should be a system-based approach in preventing severe sepsis, its burdens, and its costs. Suggestions include preventing delirium, initiating better standards of care, and involving therapists earlier to prevent immobility.

Bottom line: Severe sepsis is independently associated with enduring cognitive and physical functional declines, which strain families and our healthcare system.

Citation: Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-1794.

Furosemide on Day of Elective Noncardiac Surgery Does Not Increase Risk of Intraoperative Hypotension

Clinical question: For patients chronically treated with loop diuretics, does withholding furosemide on the day of elective noncardiac surgery prevent intraoperative hypotension?

Background: Recent studies have questioned the safety of blood-pressure-lowering medications administered on the day of surgery. Beta-blockers have been associated with an increase in strokes and death perioperatively, and angiotensin receptor blockers (ARB) are frequently withheld on the day of surgery to avoid intraoperative hypotension. The effect of loop diuretics is uncertain.

Study design: Double-blind, randomized, placebo-controlled study.

Setting: Three North American university centers.

Synopsis: One hundred ninety-three patients were instructed to take furosemide or placebo on the day they underwent noncardiac surgery. The primary outcome measure was perioperative hypotension defined as a SBP <90 mmHg for more than five minutes, a 35% drop in the mean arterial blood pressure, or the need for a vasopressor agent. The number of cardiovascular complications (acute heart failure, acute coronary syndrome, arrhythmia, acute cerebrovascular event) and deaths also were analyzed.

Concerns have been raised that loop diuretics might predispose patients to a higher risk of intraoperative hypotension during noncardiac surgery. This trial showed no significant difference in the rates of intraoperative hypotension in patients who were administered furosemide versus those who were not. Although cardiovascular complications occurred more frequently in the furosemide group, the difference was not statistically significant.

Important limitations of the study were recognized. A larger population of patients could have revealed a statistically significant difference in cardiovascular outcomes in the furosemide group. Also, an anesthetic protocol was not utilized, which raises questions about the interaction of furosemide and effect on blood pressure with certain anesthetics.

Bottom line: Administering furosemide prior to surgery in chronic users does not appreciably increase the rate of intraoperative hypotension or cardiovascular events.

Citation: Khan NA, Campbell NR, Frost SD, et al. Risk of intraoperative hypotension with loop diuretics: a randomized controlled trial. Am J Med. 2010;123(11):1059e1-1059e8.

Pediatric HM Literature

Computerized Physician Order Entry Decreases Hospitalwide Mortality

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 effect of computerized physician order entry (CPOE) on hospitalwide mortality?

Background: CPOE has been touted as a key method for improving the quality and safety of patient care. To date, however, studies have not demonstrated definitive benefits, with one study demonstrating an increase in mortality rates in a critical-care unit after CPOE implementation.

Study design: Retrospective cohort study.

Setting: Quaternary-care academic children’s hospital.

Synopsis: More than 97,000 nonobstetric patients admitted to Lucile Packard Children’s Hospital (LCPH) at Stanford University in Palo Alto, Calif., from January 2001 to April 2009 were included in the analysis. The patients were divided into pre- and postintervention groups. The intervention was defined as a “big bang” activation of CPOE on Nov. 4, 2007, affecting 90% of the inpatient beds at LCPH.

After the intervention, mean monthly unadjusted mortality rates decreased to 0.716 deaths from 1.008 per 100 discharges. After adjustment for severity of illness and a rapid-response team (which had previously been shown to decrease mortality rates), mortality rates postintervention continued to remain significantly lower.

This study revealed an impressive reduction in perhaps the ultimate outcome measure: hospitalwide mortality. The authors went to extensive lengths to adjust for potential confounding factors to include delayed implementation of CPOE in the ICUs. As with many complex process improvement efforts, the devil might be in the details of local context and culture. Thus, the software might have been less important than the manner in which the institution adapted to its functionality. Those seeking to replicate these results will need to be mindful of the requisite organizational changes in communication, order standardization, and data retrieval.

Bottom line: CPOE implementation has the potential to significantly reduce hospitalwide mortality rates.

Citation: Longhurst CA, Parast L, Sandborg CI, et al. Decrease in hospital-wide mortality rate after implementation of a commercially sold computerized physician order entry system. Pediatrics. 2010;126(1):e1-e8.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Effect of restrictive antibiotic policies on dosing timeliness
• Desired consultation format and content
• Risk of cancer associated with CT imaging
• Bleeding, mortality with aspirin after peptic ulcer bleed
• Diagnosis of lung cancer after pneumonia
• Outcomes associated with hyponatremia
• Patient awareness, interest in inpatient medication list
• Monoclonal antibodies in C. difficile

Restrictive Antimicrobial Policy Delays Administration

Clinical question: Does the approval process for restricted on-formulary antimicrobials cause a significant delay in their administration?

Background: Widespread and often unwarranted, antimicrobial use in the hospital lends itself to the development of microbial resistance and increases overall costs. To curb such practices, many hospitals require subspecialty approval prior to dispensing select broad-spectrum antimicrobials. Though shown to improve outcomes, the impact of the approval process on the timeliness of antimicrobial administration remains to be seen.

Study design: Retrospective cohort study.

Setting: Tertiary-care university hospital.

Synopsis: The study included 3,251 inpatients with computerized orders for a “stat” first dose of any of 24 pre-selected, parenteral antimicrobials. Time lag (more than one hour, and more than two hours) to nursing documentation of drug administration was separately analyzed for restricted and unrestricted antimicrobials.

Delay of more than one hour was significantly higher for restricted antimicrobials with an odds ratio of 1.49 (95% CI; 1.23-1.82), while the odds ratio for a delay of more than two hours was 1.78 (95% CI, 1.39-2.21). Also, for restricted antimicrobials, the percentage of orders delayed for more than one hour was significantly different between daytime and nighttime (when the first dose was exempt from pre-approval) orders: 46.1% versus 38.8% (P<0.001). For unrestricted drugs, delay was uniform irrespective of time of day (36.4% of daytime and 36.6% of nighttime orders were delayed more than one hour). The effect of delay in drug administration on patient outcomes was not evaluated.

Though the approval process aims in part to affect resistance patterns and overall costs, this research highlights the need to minimize the delay in administration and probably skip the approval for the first dose in critically ill patients.

Bottom line: Antibiotic approval processes can delay their administration in hospitalized patients, but the effect of this delay on patient outcomes is not yet known.

Citation: Winters BD, Thiemann DR, Brotman DJ. Impact of a restrictive antimicrobial policy on the process and timing of antimicrobial administration. J Hosp Med. 2010;5(1):E41-45.

Physicians Uphold Tenets of Effective Consultation while Highlighting Some Newer Viewpoints

Clinical question: What key features of a consultation are most desirable for physicians?

Background: With new changes in healthcare delivery, the standardization offered by the electronic health record (EHR) system will undoubtedly be confronted by the heterogeneity of clinical consultations. Determination of the various characteristics considered essential for a consultation can help standardize the processes and improve the quality of communication.

Study design: Opinion surveys with a 16-question, Web-based questionnaire about inpatient consultations.

Setting: Four Minnesota teaching hospitals affiliated with the University of Minnesota.

Synopsis: This study surveyed 651 physicians, mostly from general medicine and pediatrics (30% in-training; 54% were more than five years out of training). The response rate to the survey was 50% (323). Responses were analyzed separately for physicians predominantly requesting consultations (requesters) and those predominantly providing them (consultants).

Regarding the consultation request, the majority of consultants preferred a precise consult question (94%), contact information of the ordering provider (68%), and the urgency of consultation (66%), with telephonic communication for emergent consults (75%). Responses were similar regardless of practice site, specialty, or experience.

Regarding the consultation, more requesters desired verbal communication over written advice alone: Sixty-six percent preferred to have the rationale of the recommendations explained. They also preferred a separate recommendations section (48%) with bulleted suggestions (69%) at the top or bottom of the note (74%). Emphasis was placed on specificity of drug names, dose, and duration of therapy (80%), along with alternative options (76%). Most requesters desired a clear “signoff” note when appropriate, with a follow-up plan (74%) or scheduled appointments (44%).

Bottom line: For consultations, the majority of physicians prefer an explanation of medical decision-making, a crisp recommendation section, and specific directions for follow-up.

Citation: Boulware DR, Dekarske AS, Filice GA. Physician preferences for elements of effective consultations. J Gen Intern Med. 2010;25(1):25-30.

CT Scanning Could Be Related to a Future Risk of Cancer at a Population Level

Clinical question: Does the accelerated use of CT scans increase the future risk for radiation-related cancer?

Background: Computed tomography (CT) has come through as a powerful diagnostic and interventional imaging modality at the cost of higher radiation exposures. The potential cancer risk is minimal at an individual level; however, CT technology is used in more than 70 million scans annually. This volume can translate into a significant number of future cancers in the population.

Study design: Indirect risk modeling based on CT scan frequencies and radiation risk models.

Synopsis: Annual frequencies of CT scans (age- and sex-specific) were extracted from insurance claims. The study included 57 million scans, of which 30% were performed in adults 35 to 54 years old. The majority of scans were in females (60%).

Age-specific cancer risk for each CT scan type was estimated through published radiation risk models and national surveys. The projected number of incident cancers per 10,000 scans was highest for chest or abdominal CT angiography (CTA) and whole-body CT. Incidence was higher for females.

The CT scan frequencies were combined with the cancer risk, and it was estimated that approximately 29,000 (95% UL, 15,000-45,000) future cancers could be related to the exposure from CT scans. Uncertainty limits (UL), an estimation of the total error of measurement, accounted for statistical and subjective uncertainties. The risk was dependent on the radiation dose (chest CTA) and frequency of use (abdomen/pelvis followed by chest and head). The most common cancers were lung, colon, and leukemia.

Two-thirds of the projected cancers were in females and attributable to the higher frequency of scans in women coupled with their dual risk of breast and lung cancer with chest radiation. The results provide potential study targets for risk-reduction efforts.

Bottom line: CTA of the chest, abdomen, or pelvis could be related to risk of future cancers, especially in middle-aged females.

Citation: Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169(22):2071-2077.

Early Resumption of Low-Dose Aspirin after Peptic Ulcer Bleeding Might Be Beneficial

Clinical question: Is it safe to restart aspirin after acute gastrointestinal (GI) bleeding in patients with cardiovascular or cerebrovascular disease?

Background: The increasing cardiovascular burden in the aging population has indirectly increased aspirin-related peptic ulcer bleeding. Proton-pump inhibitors (PPI) have shown promise in reducing recurrent GI bleeding in non-aspirin-related cases. It is unclear if this protective effect applies to patients on aspirin and, if so, if aspirin resumption after endoscopic treatment is safe.

Study design: Parallel, randomized, placebo-controlled, noninferiority trial.

Setting: Single tertiary endoscopy center in Hong Kong.

Synopsis: One hundred fifty-six patients with aspirin-related peptic ulcer bleeding were selected for the study. After successful endoscopic treatment and 72 hours on pantoprazole infusion, the patients were started on oral pantoprazole for the duration of the study (eight weeks). Patients were equally randomized to receive low-dose aspirin (80 mg/d) or placebo. Primary outcome was recurrent bleeding within 30 days. Secondary outcomes included eight-week all-cause mortality, cause-specific mortality, and recurrence of cardiovascular events.

The aspirin group had a 50% higher risk of recurrent bleeding within 30 days compared with placebo (10.3% vs. 5.4%). However, for the secondary endpoints, aspirin had lower all-cause mortality (1.3% vs. 12.9%), which was not related to increased GI bleeding. On the other hand, discontinuation of aspirin and use of PPI in the placebo group did not prevent mortality related to GI complications.

The small numbers restrict interpretation of the mortality rates but offer support to the fact that the cardioprotective effects of aspirin outweigh its potential for GI bleeding. It is to be noted that these results cannot be extrapolated to higher doses of aspirin.

Bottom line: Early resumption of aspirin after successful treatment of peptic ulcer bleeding might increase the risk of rebleeding but potentially decreases overall mortality.

Citation: Sung JJ, Lau JY, Ching JY, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2010;152(1):1-9.

A Substantial Number of Elderly Patients with Pneumonia Have Pulmonary Malignancy

Clinical question: What is the incidence of, and risk factors for, diagnosis of lung cancer after discharge for pneumonia?

Background: Pneumonia-related admissions in elderly individuals have increased by nearly 20% during the past two decades. Based on the risk profile of this age group, many physicians recommend follow-up chest imaging after pneumonia to ensure resolution and exclude underlying malignancy. However, this practice is not backed by substantial evidence.

Study design: Retrospective cohort study from administrative databases of the VA system.

Setting: Veteran Affairs (VA) Health Care System.

Synopsis: More than 40,000 patients (older than 65, 98.1% male) hospitalized for pneumonia were included in the study. These patients had no pneumonia in the preceding year and did not carry a diagnosis of lung cancer. During the follow-up period of up to five years, a significant proportion (9.2%) of these patients were diagnosed with pulmonary malignancy.

Pertinent factors associated with increased risk of diagnosis included active tobacco use, COPD, and prior nonpulmonary malignancy. Interestingly, stroke, diabetes, dementia, and heart failure were associated with a lower risk of diagnosis, likely due to early mortality from these diseases prior to diagnosis of lung cancer.

Mean time to diagnosis was 297 days, with just 27% diagnosed within 30 days. On mortality analysis, 12.9% (n=5270) of the patients died within 30 days and 20.7% (n=8451) within 90 days. Thus, a period of surveillance of 30 to 90 days following pneumonia, especially in patients with risk factors, could be beneficial.

This study was limited due to the shortcomings of database analyses. Also, the predominantly male, elderly, veteran population restricts extrapolation to the general population.

Bottom line: Patients with risk factors for lung cancer might benefit from surveillance chest imaging after hospitalization for pneumonia to rule out an underlying malignancy.

Citation: Mortensen EM, Copeland LA, Pugh MJ, et al. Diagnosis of pulmonary malignancy after hospitalization for pneumonia. Am J Med. 2010:123(1):66-71.

Hospital-Associated Hyponatremia of Any Severity Adversely Impacts Mortality and Financial Metrics

Clinical question: Does hyponatremia during a hospitalization prophesize a worse outcome?

Study design: Retrospective cohort study from 2002-2007.

Setting: Urban academic medical center.

Synopsis: This study included 53,236 adults based on the presence of admission or subsequent hyponatremia (defined as [Na+] <138 mEq/L). The patients were classified as community-acquired (CAH=37.9%), hospital-aggravated (5.7%), or hospital-acquired hyponatremia (HAH=38.2%).

Across all subgroups, all types of hyponatremia were independently associated with worse primary outcomes, including an increase in hospital mortality (CAH 52%, HAH 66%), prolongation of hospital stay, and discharge to a facility. Also, for the same [Na+], HAH had significantly increased mortality compared with CAH. Though the elderly were more prone to develop hyponatremia, patients younger than 65 had worse outcomes.

The severity of hyponatremia prognosticated adverse outcomes. The liberal definition of hyponatremia, as opposed to the current standard of <135 mEq/L, explains the large numbers in prevalence. However, even mild hyponatremia (133 mEq/L to 137) was linked to poor outcomes (adjusted OR 1.34; CI 1.18-1.51).

The study weaknesses include the use of administrative codes to identify comorbidities, less applicability to outpatient setting, and lack of evaluation of outcomes postdischarge. However, the robust numbers do establish inpatient hyponatremia as a marker of worse outcomes.

Bottom line: Inpatient hyponatremia of any severity is a marker of increased mortality and excessive financial burden.

Citation: Wald R, Jaber BL, Price LL, Upadhyay A, Madias NE. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med. 2010;170(3):294-302.

Patients Lack Awareness and Prefer to Be Updated Regarding Their Inpatient Medications

Clinical question: Is patient knowledge of their medications deficient, and does this reflect a lack of desire to be involved in the medication reconciliation process?

Background: Medication errors remain a significant healthcare problem due to their potential to increase morbidity. For medication administration errors, apart from the dispensing pharmacist and the nurses, patients could be the final checkpoint to ensure medication safety. However, their awareness and enthusiasm to participate has not been adequately assessed in the literature.

Study design: A cross-sectional study using individual surveys to assess awareness and attitudes regarding inpatient medications.

Setting: Single tertiary-care academic teaching hospital.

Synopsis: Fifty cognitively intact adult patients were consented for the study. Of these, 54% provided an accurate recollection of their outpatient medications. When they were surveyed regarding inpatient medications, 96% omitted at least one medication, with the average of 6.8 medication omissions. This was noted to correlate with age >65 years. Also, 44% erroneously presumed they were on a medication while they were in the hospital, even though they weren’t.

When attitudes were surveyed, most of the patients would have preferred to get an inpatient medication list (78%) with the goal of improving their satisfaction (81%) and reducing errors (94%). Also, no association was found between patients’ errors of omission and their reported desire to be involved in the medication safety process.

This small study was limited to cognitively intact patients only. Also, the relatively younger age might cause an overestimation of patient interest in participation. However, the results highlight key medication reconciliation issues. Although patient involvement is desirable, a systematic program of educating them about their medications would be required to make their feedback effective and useful.

Bottom line: Healthy patients might be unaware of their exact hospital medications but prefer to be kept in the loop.

Citation: Cumbler E, Wald H, Kutner J. Lack of patient knowledge regarding hospital medications. J Hosp Med. 2010;5(2):83-86.

Monoclonal Antibodies against Clostridium difficile Toxins Prevent Recurrence

Clinical question: Are human monoclonal antibodies against C. difficile toxin A (CDA1) and B (CDB1) effective in preventing recurrence of C. diff infection (CDI)?

Background: Widespread use of antibiotics, coupled with the emergence of the hypervirulent (B1/NAP1/027) strain of C. diff, has altered the epidemiology of CDI. Even with effective treatment regimens, there is an escalation in severity, treatment failures, and recurrences. Antibodies against the C. diff toxins are being evaluated as the next frontier in treatment of CDI.

Study design: Phase 2 randomized, double-blind, placebo-controlled trial.

Setting: Thirty study centers in Canada and the U.S.

Synopsis: Two hundred patients with laboratory documented CDI on standard therapy with either metronidazole or vancomycin were randomized to receive a single IV infusion of combined monoclonal antibodies against CDA1 and CDB1 (n=101) or a normal saline placebo infusion (n=99). Patients were followed for 84 days with daily stool counts and intermittent blood samples for immunogenicity analysis.

The primary endpoint of recurrence of laboratory-proven C. diff diarrhea was significantly lower in the monoclonal antibody group (7% vs. 25% in placebo. 95% CI, 7-29; P <0.001). In a subgroup analysis of the epidemic BI/NAP1/027 strain, this favorable association persisted (8% vs. 32%). Recurrence in the antibody group was seen more in elderly patients hospitalized with a higher severity of underlying disease.

Secondary endpoints relating to the initial episode of CDI including treatment failure, severity of diarrhea, and duration to resolution were not significantly different between the two groups. Fewer accounts of serious adverse events were documented in the antibody group (18 patients vs. 28 patients in placebo, P=0.09), and immunogenicity was not detected in any patient.

Bottom line: Monoclonal antibody infusion against C. diff toxins reduces recurrence of infection, even with a hypervirulent (B1/NAP1/027) strain, without any significant adverse events.

Citation: Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010; 362(3):197-205. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

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

Rectal Colonization with S. aureus Associated with Skin Abscesses

Clinical question: Is rectal colonization with Staphylococcus aureus more strongly associated with staphylococcal skin abscesses than nasal colonization?

Background: Staphylococcal skin and soft tissue infections have dramatically increased in recent years. While increased rates of nasal colonization with S. aureus have also been noted, a strong association with skin infections in children has not been established. The relationship between staphylococcal colonization of other body sites and skin infection is unknown.

Study design: Prospective cohort study.

Setting: Tertiary-care hospital in Buffalo, N.Y.

Synopsis: Sixty children, 0 to 18 years of age, requiring surgical drainage of S. aureus skin abscesses and 90 children undergoing other surgical procedures were enrolled consecutively. Rectal, nasal, and abscess (if applicable) cultures were obtained on all patients. Enrollment ceased when notably different rates of rectal colonization were recorded.

Rectal cultures were significantly more likely to be positive in the abscess group than the control group (47% vs. 1%; P<0.0001), while rates of nasal colonization were similar (27% vs. 21%; P=0.44). Abscess isolates were identical to rectal isolates in 88% of cases and nasal isolates in 75% of cases.

Other findings included a 60% prevalence of methicillin-resistant S. aureus (MRSA) in the abscess group. Fifty-nine of the 60 abscess isolates contained Panton-Valentine leukocidin genes; 57 were pulsed-field type USA300; and all 60 contained the staphylococcal cassette chromosome mec type IVa.

Given this representative sample of community-associated staphylococcal disease, these findings suggest that a focus on nasal carriage of S. aureus might be misguided.

Bottom Line: Rectal colonization with S. aureus better predicts skin abscess isolate than nasal carriage.

Citation: Faden H, Lesse AJ, Trask J, et al. Importance of colonization site in the current epidemic of staphylococcal skin abscesses. Pediatrics. 2010;125(3):e618-e624.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Effect of restrictive antibiotic policies on dosing timeliness
• Desired consultation format and content
• Risk of cancer associated with CT imaging
• Bleeding, mortality with aspirin after peptic ulcer bleed
• Diagnosis of lung cancer after pneumonia
• Outcomes associated with hyponatremia
• Patient awareness, interest in inpatient medication list
• Monoclonal antibodies in C. difficile

Restrictive Antimicrobial Policy Delays Administration

Clinical question: Does the approval process for restricted on-formulary antimicrobials cause a significant delay in their administration?

Background: Widespread and often unwarranted, antimicrobial use in the hospital lends itself to the development of microbial resistance and increases overall costs. To curb such practices, many hospitals require subspecialty approval prior to dispensing select broad-spectrum antimicrobials. Though shown to improve outcomes, the impact of the approval process on the timeliness of antimicrobial administration remains to be seen.

Study design: Retrospective cohort study.

Setting: Tertiary-care university hospital.

Synopsis: The study included 3,251 inpatients with computerized orders for a “stat” first dose of any of 24 pre-selected, parenteral antimicrobials. Time lag (more than one hour, and more than two hours) to nursing documentation of drug administration was separately analyzed for restricted and unrestricted antimicrobials.

Delay of more than one hour was significantly higher for restricted antimicrobials with an odds ratio of 1.49 (95% CI; 1.23-1.82), while the odds ratio for a delay of more than two hours was 1.78 (95% CI, 1.39-2.21). Also, for restricted antimicrobials, the percentage of orders delayed for more than one hour was significantly different between daytime and nighttime (when the first dose was exempt from pre-approval) orders: 46.1% versus 38.8% (P<0.001). For unrestricted drugs, delay was uniform irrespective of time of day (36.4% of daytime and 36.6% of nighttime orders were delayed more than one hour). The effect of delay in drug administration on patient outcomes was not evaluated.

Though the approval process aims in part to affect resistance patterns and overall costs, this research highlights the need to minimize the delay in administration and probably skip the approval for the first dose in critically ill patients.

Bottom line: Antibiotic approval processes can delay their administration in hospitalized patients, but the effect of this delay on patient outcomes is not yet known.

Citation: Winters BD, Thiemann DR, Brotman DJ. Impact of a restrictive antimicrobial policy on the process and timing of antimicrobial administration. J Hosp Med. 2010;5(1):E41-45.

Physicians Uphold Tenets of Effective Consultation while Highlighting Some Newer Viewpoints

Clinical question: What key features of a consultation are most desirable for physicians?

Background: With new changes in healthcare delivery, the standardization offered by the electronic health record (EHR) system will undoubtedly be confronted by the heterogeneity of clinical consultations. Determination of the various characteristics considered essential for a consultation can help standardize the processes and improve the quality of communication.

Study design: Opinion surveys with a 16-question, Web-based questionnaire about inpatient consultations.

Setting: Four Minnesota teaching hospitals affiliated with the University of Minnesota.

Synopsis: This study surveyed 651 physicians, mostly from general medicine and pediatrics (30% in-training; 54% were more than five years out of training). The response rate to the survey was 50% (323). Responses were analyzed separately for physicians predominantly requesting consultations (requesters) and those predominantly providing them (consultants).

Regarding the consultation request, the majority of consultants preferred a precise consult question (94%), contact information of the ordering provider (68%), and the urgency of consultation (66%), with telephonic communication for emergent consults (75%). Responses were similar regardless of practice site, specialty, or experience.

Regarding the consultation, more requesters desired verbal communication over written advice alone: Sixty-six percent preferred to have the rationale of the recommendations explained. They also preferred a separate recommendations section (48%) with bulleted suggestions (69%) at the top or bottom of the note (74%). Emphasis was placed on specificity of drug names, dose, and duration of therapy (80%), along with alternative options (76%). Most requesters desired a clear “signoff” note when appropriate, with a follow-up plan (74%) or scheduled appointments (44%).

Bottom line: For consultations, the majority of physicians prefer an explanation of medical decision-making, a crisp recommendation section, and specific directions for follow-up.

Citation: Boulware DR, Dekarske AS, Filice GA. Physician preferences for elements of effective consultations. J Gen Intern Med. 2010;25(1):25-30.

CT Scanning Could Be Related to a Future Risk of Cancer at a Population Level

Clinical question: Does the accelerated use of CT scans increase the future risk for radiation-related cancer?

Background: Computed tomography (CT) has come through as a powerful diagnostic and interventional imaging modality at the cost of higher radiation exposures. The potential cancer risk is minimal at an individual level; however, CT technology is used in more than 70 million scans annually. This volume can translate into a significant number of future cancers in the population.

Study design: Indirect risk modeling based on CT scan frequencies and radiation risk models.

Synopsis: Annual frequencies of CT scans (age- and sex-specific) were extracted from insurance claims. The study included 57 million scans, of which 30% were performed in adults 35 to 54 years old. The majority of scans were in females (60%).

Age-specific cancer risk for each CT scan type was estimated through published radiation risk models and national surveys. The projected number of incident cancers per 10,000 scans was highest for chest or abdominal CT angiography (CTA) and whole-body CT. Incidence was higher for females.

The CT scan frequencies were combined with the cancer risk, and it was estimated that approximately 29,000 (95% UL, 15,000-45,000) future cancers could be related to the exposure from CT scans. Uncertainty limits (UL), an estimation of the total error of measurement, accounted for statistical and subjective uncertainties. The risk was dependent on the radiation dose (chest CTA) and frequency of use (abdomen/pelvis followed by chest and head). The most common cancers were lung, colon, and leukemia.

Two-thirds of the projected cancers were in females and attributable to the higher frequency of scans in women coupled with their dual risk of breast and lung cancer with chest radiation. The results provide potential study targets for risk-reduction efforts.

Bottom line: CTA of the chest, abdomen, or pelvis could be related to risk of future cancers, especially in middle-aged females.

Citation: Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169(22):2071-2077.

Early Resumption of Low-Dose Aspirin after Peptic Ulcer Bleeding Might Be Beneficial

Clinical question: Is it safe to restart aspirin after acute gastrointestinal (GI) bleeding in patients with cardiovascular or cerebrovascular disease?

Background: The increasing cardiovascular burden in the aging population has indirectly increased aspirin-related peptic ulcer bleeding. Proton-pump inhibitors (PPI) have shown promise in reducing recurrent GI bleeding in non-aspirin-related cases. It is unclear if this protective effect applies to patients on aspirin and, if so, if aspirin resumption after endoscopic treatment is safe.

Study design: Parallel, randomized, placebo-controlled, noninferiority trial.

Setting: Single tertiary endoscopy center in Hong Kong.

Synopsis: One hundred fifty-six patients with aspirin-related peptic ulcer bleeding were selected for the study. After successful endoscopic treatment and 72 hours on pantoprazole infusion, the patients were started on oral pantoprazole for the duration of the study (eight weeks). Patients were equally randomized to receive low-dose aspirin (80 mg/d) or placebo. Primary outcome was recurrent bleeding within 30 days. Secondary outcomes included eight-week all-cause mortality, cause-specific mortality, and recurrence of cardiovascular events.

The aspirin group had a 50% higher risk of recurrent bleeding within 30 days compared with placebo (10.3% vs. 5.4%). However, for the secondary endpoints, aspirin had lower all-cause mortality (1.3% vs. 12.9%), which was not related to increased GI bleeding. On the other hand, discontinuation of aspirin and use of PPI in the placebo group did not prevent mortality related to GI complications.

The small numbers restrict interpretation of the mortality rates but offer support to the fact that the cardioprotective effects of aspirin outweigh its potential for GI bleeding. It is to be noted that these results cannot be extrapolated to higher doses of aspirin.

Bottom line: Early resumption of aspirin after successful treatment of peptic ulcer bleeding might increase the risk of rebleeding but potentially decreases overall mortality.

Citation: Sung JJ, Lau JY, Ching JY, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2010;152(1):1-9.

A Substantial Number of Elderly Patients with Pneumonia Have Pulmonary Malignancy

Clinical question: What is the incidence of, and risk factors for, diagnosis of lung cancer after discharge for pneumonia?

Background: Pneumonia-related admissions in elderly individuals have increased by nearly 20% during the past two decades. Based on the risk profile of this age group, many physicians recommend follow-up chest imaging after pneumonia to ensure resolution and exclude underlying malignancy. However, this practice is not backed by substantial evidence.

Study design: Retrospective cohort study from administrative databases of the VA system.

Setting: Veteran Affairs (VA) Health Care System.

Synopsis: More than 40,000 patients (older than 65, 98.1% male) hospitalized for pneumonia were included in the study. These patients had no pneumonia in the preceding year and did not carry a diagnosis of lung cancer. During the follow-up period of up to five years, a significant proportion (9.2%) of these patients were diagnosed with pulmonary malignancy.

Pertinent factors associated with increased risk of diagnosis included active tobacco use, COPD, and prior nonpulmonary malignancy. Interestingly, stroke, diabetes, dementia, and heart failure were associated with a lower risk of diagnosis, likely due to early mortality from these diseases prior to diagnosis of lung cancer.

Mean time to diagnosis was 297 days, with just 27% diagnosed within 30 days. On mortality analysis, 12.9% (n=5270) of the patients died within 30 days and 20.7% (n=8451) within 90 days. Thus, a period of surveillance of 30 to 90 days following pneumonia, especially in patients with risk factors, could be beneficial.

This study was limited due to the shortcomings of database analyses. Also, the predominantly male, elderly, veteran population restricts extrapolation to the general population.

Bottom line: Patients with risk factors for lung cancer might benefit from surveillance chest imaging after hospitalization for pneumonia to rule out an underlying malignancy.

Citation: Mortensen EM, Copeland LA, Pugh MJ, et al. Diagnosis of pulmonary malignancy after hospitalization for pneumonia. Am J Med. 2010:123(1):66-71.

Hospital-Associated Hyponatremia of Any Severity Adversely Impacts Mortality and Financial Metrics

Clinical question: Does hyponatremia during a hospitalization prophesize a worse outcome?

Study design: Retrospective cohort study from 2002-2007.

Setting: Urban academic medical center.

Synopsis: This study included 53,236 adults based on the presence of admission or subsequent hyponatremia (defined as [Na+] <138 mEq/L). The patients were classified as community-acquired (CAH=37.9%), hospital-aggravated (5.7%), or hospital-acquired hyponatremia (HAH=38.2%).

Across all subgroups, all types of hyponatremia were independently associated with worse primary outcomes, including an increase in hospital mortality (CAH 52%, HAH 66%), prolongation of hospital stay, and discharge to a facility. Also, for the same [Na+], HAH had significantly increased mortality compared with CAH. Though the elderly were more prone to develop hyponatremia, patients younger than 65 had worse outcomes.

The severity of hyponatremia prognosticated adverse outcomes. The liberal definition of hyponatremia, as opposed to the current standard of <135 mEq/L, explains the large numbers in prevalence. However, even mild hyponatremia (133 mEq/L to 137) was linked to poor outcomes (adjusted OR 1.34; CI 1.18-1.51).

The study weaknesses include the use of administrative codes to identify comorbidities, less applicability to outpatient setting, and lack of evaluation of outcomes postdischarge. However, the robust numbers do establish inpatient hyponatremia as a marker of worse outcomes.

Bottom line: Inpatient hyponatremia of any severity is a marker of increased mortality and excessive financial burden.

Citation: Wald R, Jaber BL, Price LL, Upadhyay A, Madias NE. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med. 2010;170(3):294-302.

Patients Lack Awareness and Prefer to Be Updated Regarding Their Inpatient Medications

Clinical question: Is patient knowledge of their medications deficient, and does this reflect a lack of desire to be involved in the medication reconciliation process?

Background: Medication errors remain a significant healthcare problem due to their potential to increase morbidity. For medication administration errors, apart from the dispensing pharmacist and the nurses, patients could be the final checkpoint to ensure medication safety. However, their awareness and enthusiasm to participate has not been adequately assessed in the literature.

Study design: A cross-sectional study using individual surveys to assess awareness and attitudes regarding inpatient medications.

Setting: Single tertiary-care academic teaching hospital.

Synopsis: Fifty cognitively intact adult patients were consented for the study. Of these, 54% provided an accurate recollection of their outpatient medications. When they were surveyed regarding inpatient medications, 96% omitted at least one medication, with the average of 6.8 medication omissions. This was noted to correlate with age >65 years. Also, 44% erroneously presumed they were on a medication while they were in the hospital, even though they weren’t.

When attitudes were surveyed, most of the patients would have preferred to get an inpatient medication list (78%) with the goal of improving their satisfaction (81%) and reducing errors (94%). Also, no association was found between patients’ errors of omission and their reported desire to be involved in the medication safety process.

This small study was limited to cognitively intact patients only. Also, the relatively younger age might cause an overestimation of patient interest in participation. However, the results highlight key medication reconciliation issues. Although patient involvement is desirable, a systematic program of educating them about their medications would be required to make their feedback effective and useful.

Bottom line: Healthy patients might be unaware of their exact hospital medications but prefer to be kept in the loop.

Citation: Cumbler E, Wald H, Kutner J. Lack of patient knowledge regarding hospital medications. J Hosp Med. 2010;5(2):83-86.

Monoclonal Antibodies against Clostridium difficile Toxins Prevent Recurrence

Clinical question: Are human monoclonal antibodies against C. difficile toxin A (CDA1) and B (CDB1) effective in preventing recurrence of C. diff infection (CDI)?

Background: Widespread use of antibiotics, coupled with the emergence of the hypervirulent (B1/NAP1/027) strain of C. diff, has altered the epidemiology of CDI. Even with effective treatment regimens, there is an escalation in severity, treatment failures, and recurrences. Antibodies against the C. diff toxins are being evaluated as the next frontier in treatment of CDI.

Study design: Phase 2 randomized, double-blind, placebo-controlled trial.

Setting: Thirty study centers in Canada and the U.S.

Synopsis: Two hundred patients with laboratory documented CDI on standard therapy with either metronidazole or vancomycin were randomized to receive a single IV infusion of combined monoclonal antibodies against CDA1 and CDB1 (n=101) or a normal saline placebo infusion (n=99). Patients were followed for 84 days with daily stool counts and intermittent blood samples for immunogenicity analysis.

The primary endpoint of recurrence of laboratory-proven C. diff diarrhea was significantly lower in the monoclonal antibody group (7% vs. 25% in placebo. 95% CI, 7-29; P <0.001). In a subgroup analysis of the epidemic BI/NAP1/027 strain, this favorable association persisted (8% vs. 32%). Recurrence in the antibody group was seen more in elderly patients hospitalized with a higher severity of underlying disease.

Secondary endpoints relating to the initial episode of CDI including treatment failure, severity of diarrhea, and duration to resolution were not significantly different between the two groups. Fewer accounts of serious adverse events were documented in the antibody group (18 patients vs. 28 patients in placebo, P=0.09), and immunogenicity was not detected in any patient.

Bottom line: Monoclonal antibody infusion against C. diff toxins reduces recurrence of infection, even with a hypervirulent (B1/NAP1/027) strain, without any significant adverse events.

Citation: Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010; 362(3):197-205. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

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

Rectal Colonization with S. aureus Associated with Skin Abscesses

Clinical question: Is rectal colonization with Staphylococcus aureus more strongly associated with staphylococcal skin abscesses than nasal colonization?

Background: Staphylococcal skin and soft tissue infections have dramatically increased in recent years. While increased rates of nasal colonization with S. aureus have also been noted, a strong association with skin infections in children has not been established. The relationship between staphylococcal colonization of other body sites and skin infection is unknown.

Study design: Prospective cohort study.

Setting: Tertiary-care hospital in Buffalo, N.Y.

Synopsis: Sixty children, 0 to 18 years of age, requiring surgical drainage of S. aureus skin abscesses and 90 children undergoing other surgical procedures were enrolled consecutively. Rectal, nasal, and abscess (if applicable) cultures were obtained on all patients. Enrollment ceased when notably different rates of rectal colonization were recorded.

Rectal cultures were significantly more likely to be positive in the abscess group than the control group (47% vs. 1%; P<0.0001), while rates of nasal colonization were similar (27% vs. 21%; P=0.44). Abscess isolates were identical to rectal isolates in 88% of cases and nasal isolates in 75% of cases.

Other findings included a 60% prevalence of methicillin-resistant S. aureus (MRSA) in the abscess group. Fifty-nine of the 60 abscess isolates contained Panton-Valentine leukocidin genes; 57 were pulsed-field type USA300; and all 60 contained the staphylococcal cassette chromosome mec type IVa.

Given this representative sample of community-associated staphylococcal disease, these findings suggest that a focus on nasal carriage of S. aureus might be misguided.

Bottom Line: Rectal colonization with S. aureus better predicts skin abscess isolate than nasal carriage.

Citation: Faden H, Lesse AJ, Trask J, et al. Importance of colonization site in the current epidemic of staphylococcal skin abscesses. Pediatrics. 2010;125(3):e618-e624.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Effect of restrictive antibiotic policies on dosing timeliness
• Desired consultation format and content
• Risk of cancer associated with CT imaging
• Bleeding, mortality with aspirin after peptic ulcer bleed
• Diagnosis of lung cancer after pneumonia
• Outcomes associated with hyponatremia
• Patient awareness, interest in inpatient medication list
• Monoclonal antibodies in C. difficile

Restrictive Antimicrobial Policy Delays Administration

Clinical question: Does the approval process for restricted on-formulary antimicrobials cause a significant delay in their administration?

Background: Widespread and often unwarranted, antimicrobial use in the hospital lends itself to the development of microbial resistance and increases overall costs. To curb such practices, many hospitals require subspecialty approval prior to dispensing select broad-spectrum antimicrobials. Though shown to improve outcomes, the impact of the approval process on the timeliness of antimicrobial administration remains to be seen.

Study design: Retrospective cohort study.

Setting: Tertiary-care university hospital.

Synopsis: The study included 3,251 inpatients with computerized orders for a “stat” first dose of any of 24 pre-selected, parenteral antimicrobials. Time lag (more than one hour, and more than two hours) to nursing documentation of drug administration was separately analyzed for restricted and unrestricted antimicrobials.

Delay of more than one hour was significantly higher for restricted antimicrobials with an odds ratio of 1.49 (95% CI; 1.23-1.82), while the odds ratio for a delay of more than two hours was 1.78 (95% CI, 1.39-2.21). Also, for restricted antimicrobials, the percentage of orders delayed for more than one hour was significantly different between daytime and nighttime (when the first dose was exempt from pre-approval) orders: 46.1% versus 38.8% (P<0.001). For unrestricted drugs, delay was uniform irrespective of time of day (36.4% of daytime and 36.6% of nighttime orders were delayed more than one hour). The effect of delay in drug administration on patient outcomes was not evaluated.

Though the approval process aims in part to affect resistance patterns and overall costs, this research highlights the need to minimize the delay in administration and probably skip the approval for the first dose in critically ill patients.

Bottom line: Antibiotic approval processes can delay their administration in hospitalized patients, but the effect of this delay on patient outcomes is not yet known.

Citation: Winters BD, Thiemann DR, Brotman DJ. Impact of a restrictive antimicrobial policy on the process and timing of antimicrobial administration. J Hosp Med. 2010;5(1):E41-45.

Physicians Uphold Tenets of Effective Consultation while Highlighting Some Newer Viewpoints

Clinical question: What key features of a consultation are most desirable for physicians?

Background: With new changes in healthcare delivery, the standardization offered by the electronic health record (EHR) system will undoubtedly be confronted by the heterogeneity of clinical consultations. Determination of the various characteristics considered essential for a consultation can help standardize the processes and improve the quality of communication.

Study design: Opinion surveys with a 16-question, Web-based questionnaire about inpatient consultations.

Setting: Four Minnesota teaching hospitals affiliated with the University of Minnesota.

Synopsis: This study surveyed 651 physicians, mostly from general medicine and pediatrics (30% in-training; 54% were more than five years out of training). The response rate to the survey was 50% (323). Responses were analyzed separately for physicians predominantly requesting consultations (requesters) and those predominantly providing them (consultants).

Regarding the consultation request, the majority of consultants preferred a precise consult question (94%), contact information of the ordering provider (68%), and the urgency of consultation (66%), with telephonic communication for emergent consults (75%). Responses were similar regardless of practice site, specialty, or experience.

Regarding the consultation, more requesters desired verbal communication over written advice alone: Sixty-six percent preferred to have the rationale of the recommendations explained. They also preferred a separate recommendations section (48%) with bulleted suggestions (69%) at the top or bottom of the note (74%). Emphasis was placed on specificity of drug names, dose, and duration of therapy (80%), along with alternative options (76%). Most requesters desired a clear “signoff” note when appropriate, with a follow-up plan (74%) or scheduled appointments (44%).

Bottom line: For consultations, the majority of physicians prefer an explanation of medical decision-making, a crisp recommendation section, and specific directions for follow-up.

Citation: Boulware DR, Dekarske AS, Filice GA. Physician preferences for elements of effective consultations. J Gen Intern Med. 2010;25(1):25-30.

CT Scanning Could Be Related to a Future Risk of Cancer at a Population Level

Clinical question: Does the accelerated use of CT scans increase the future risk for radiation-related cancer?

Background: Computed tomography (CT) has come through as a powerful diagnostic and interventional imaging modality at the cost of higher radiation exposures. The potential cancer risk is minimal at an individual level; however, CT technology is used in more than 70 million scans annually. This volume can translate into a significant number of future cancers in the population.

Study design: Indirect risk modeling based on CT scan frequencies and radiation risk models.

Synopsis: Annual frequencies of CT scans (age- and sex-specific) were extracted from insurance claims. The study included 57 million scans, of which 30% were performed in adults 35 to 54 years old. The majority of scans were in females (60%).

Age-specific cancer risk for each CT scan type was estimated through published radiation risk models and national surveys. The projected number of incident cancers per 10,000 scans was highest for chest or abdominal CT angiography (CTA) and whole-body CT. Incidence was higher for females.

The CT scan frequencies were combined with the cancer risk, and it was estimated that approximately 29,000 (95% UL, 15,000-45,000) future cancers could be related to the exposure from CT scans. Uncertainty limits (UL), an estimation of the total error of measurement, accounted for statistical and subjective uncertainties. The risk was dependent on the radiation dose (chest CTA) and frequency of use (abdomen/pelvis followed by chest and head). The most common cancers were lung, colon, and leukemia.

Two-thirds of the projected cancers were in females and attributable to the higher frequency of scans in women coupled with their dual risk of breast and lung cancer with chest radiation. The results provide potential study targets for risk-reduction efforts.

Bottom line: CTA of the chest, abdomen, or pelvis could be related to risk of future cancers, especially in middle-aged females.

Citation: Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169(22):2071-2077.

Early Resumption of Low-Dose Aspirin after Peptic Ulcer Bleeding Might Be Beneficial

Clinical question: Is it safe to restart aspirin after acute gastrointestinal (GI) bleeding in patients with cardiovascular or cerebrovascular disease?

Background: The increasing cardiovascular burden in the aging population has indirectly increased aspirin-related peptic ulcer bleeding. Proton-pump inhibitors (PPI) have shown promise in reducing recurrent GI bleeding in non-aspirin-related cases. It is unclear if this protective effect applies to patients on aspirin and, if so, if aspirin resumption after endoscopic treatment is safe.

Study design: Parallel, randomized, placebo-controlled, noninferiority trial.

Setting: Single tertiary endoscopy center in Hong Kong.

Synopsis: One hundred fifty-six patients with aspirin-related peptic ulcer bleeding were selected for the study. After successful endoscopic treatment and 72 hours on pantoprazole infusion, the patients were started on oral pantoprazole for the duration of the study (eight weeks). Patients were equally randomized to receive low-dose aspirin (80 mg/d) or placebo. Primary outcome was recurrent bleeding within 30 days. Secondary outcomes included eight-week all-cause mortality, cause-specific mortality, and recurrence of cardiovascular events.

The aspirin group had a 50% higher risk of recurrent bleeding within 30 days compared with placebo (10.3% vs. 5.4%). However, for the secondary endpoints, aspirin had lower all-cause mortality (1.3% vs. 12.9%), which was not related to increased GI bleeding. On the other hand, discontinuation of aspirin and use of PPI in the placebo group did not prevent mortality related to GI complications.

The small numbers restrict interpretation of the mortality rates but offer support to the fact that the cardioprotective effects of aspirin outweigh its potential for GI bleeding. It is to be noted that these results cannot be extrapolated to higher doses of aspirin.

Bottom line: Early resumption of aspirin after successful treatment of peptic ulcer bleeding might increase the risk of rebleeding but potentially decreases overall mortality.

Citation: Sung JJ, Lau JY, Ching JY, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2010;152(1):1-9.

A Substantial Number of Elderly Patients with Pneumonia Have Pulmonary Malignancy

Clinical question: What is the incidence of, and risk factors for, diagnosis of lung cancer after discharge for pneumonia?

Background: Pneumonia-related admissions in elderly individuals have increased by nearly 20% during the past two decades. Based on the risk profile of this age group, many physicians recommend follow-up chest imaging after pneumonia to ensure resolution and exclude underlying malignancy. However, this practice is not backed by substantial evidence.

Study design: Retrospective cohort study from administrative databases of the VA system.

Setting: Veteran Affairs (VA) Health Care System.

Synopsis: More than 40,000 patients (older than 65, 98.1% male) hospitalized for pneumonia were included in the study. These patients had no pneumonia in the preceding year and did not carry a diagnosis of lung cancer. During the follow-up period of up to five years, a significant proportion (9.2%) of these patients were diagnosed with pulmonary malignancy.

Pertinent factors associated with increased risk of diagnosis included active tobacco use, COPD, and prior nonpulmonary malignancy. Interestingly, stroke, diabetes, dementia, and heart failure were associated with a lower risk of diagnosis, likely due to early mortality from these diseases prior to diagnosis of lung cancer.

Mean time to diagnosis was 297 days, with just 27% diagnosed within 30 days. On mortality analysis, 12.9% (n=5270) of the patients died within 30 days and 20.7% (n=8451) within 90 days. Thus, a period of surveillance of 30 to 90 days following pneumonia, especially in patients with risk factors, could be beneficial.

This study was limited due to the shortcomings of database analyses. Also, the predominantly male, elderly, veteran population restricts extrapolation to the general population.

Bottom line: Patients with risk factors for lung cancer might benefit from surveillance chest imaging after hospitalization for pneumonia to rule out an underlying malignancy.

Citation: Mortensen EM, Copeland LA, Pugh MJ, et al. Diagnosis of pulmonary malignancy after hospitalization for pneumonia. Am J Med. 2010:123(1):66-71.

Hospital-Associated Hyponatremia of Any Severity Adversely Impacts Mortality and Financial Metrics

Clinical question: Does hyponatremia during a hospitalization prophesize a worse outcome?

Study design: Retrospective cohort study from 2002-2007.

Setting: Urban academic medical center.

Synopsis: This study included 53,236 adults based on the presence of admission or subsequent hyponatremia (defined as [Na+] <138 mEq/L). The patients were classified as community-acquired (CAH=37.9%), hospital-aggravated (5.7%), or hospital-acquired hyponatremia (HAH=38.2%).

Across all subgroups, all types of hyponatremia were independently associated with worse primary outcomes, including an increase in hospital mortality (CAH 52%, HAH 66%), prolongation of hospital stay, and discharge to a facility. Also, for the same [Na+], HAH had significantly increased mortality compared with CAH. Though the elderly were more prone to develop hyponatremia, patients younger than 65 had worse outcomes.

The severity of hyponatremia prognosticated adverse outcomes. The liberal definition of hyponatremia, as opposed to the current standard of <135 mEq/L, explains the large numbers in prevalence. However, even mild hyponatremia (133 mEq/L to 137) was linked to poor outcomes (adjusted OR 1.34; CI 1.18-1.51).

The study weaknesses include the use of administrative codes to identify comorbidities, less applicability to outpatient setting, and lack of evaluation of outcomes postdischarge. However, the robust numbers do establish inpatient hyponatremia as a marker of worse outcomes.

Bottom line: Inpatient hyponatremia of any severity is a marker of increased mortality and excessive financial burden.

Citation: Wald R, Jaber BL, Price LL, Upadhyay A, Madias NE. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med. 2010;170(3):294-302.

Patients Lack Awareness and Prefer to Be Updated Regarding Their Inpatient Medications

Clinical question: Is patient knowledge of their medications deficient, and does this reflect a lack of desire to be involved in the medication reconciliation process?

Background: Medication errors remain a significant healthcare problem due to their potential to increase morbidity. For medication administration errors, apart from the dispensing pharmacist and the nurses, patients could be the final checkpoint to ensure medication safety. However, their awareness and enthusiasm to participate has not been adequately assessed in the literature.

Study design: A cross-sectional study using individual surveys to assess awareness and attitudes regarding inpatient medications.

Setting: Single tertiary-care academic teaching hospital.

Synopsis: Fifty cognitively intact adult patients were consented for the study. Of these, 54% provided an accurate recollection of their outpatient medications. When they were surveyed regarding inpatient medications, 96% omitted at least one medication, with the average of 6.8 medication omissions. This was noted to correlate with age >65 years. Also, 44% erroneously presumed they were on a medication while they were in the hospital, even though they weren’t.

When attitudes were surveyed, most of the patients would have preferred to get an inpatient medication list (78%) with the goal of improving their satisfaction (81%) and reducing errors (94%). Also, no association was found between patients’ errors of omission and their reported desire to be involved in the medication safety process.

This small study was limited to cognitively intact patients only. Also, the relatively younger age might cause an overestimation of patient interest in participation. However, the results highlight key medication reconciliation issues. Although patient involvement is desirable, a systematic program of educating them about their medications would be required to make their feedback effective and useful.

Bottom line: Healthy patients might be unaware of their exact hospital medications but prefer to be kept in the loop.

Citation: Cumbler E, Wald H, Kutner J. Lack of patient knowledge regarding hospital medications. J Hosp Med. 2010;5(2):83-86.

Monoclonal Antibodies against Clostridium difficile Toxins Prevent Recurrence

Clinical question: Are human monoclonal antibodies against C. difficile toxin A (CDA1) and B (CDB1) effective in preventing recurrence of C. diff infection (CDI)?

Background: Widespread use of antibiotics, coupled with the emergence of the hypervirulent (B1/NAP1/027) strain of C. diff, has altered the epidemiology of CDI. Even with effective treatment regimens, there is an escalation in severity, treatment failures, and recurrences. Antibodies against the C. diff toxins are being evaluated as the next frontier in treatment of CDI.

Study design: Phase 2 randomized, double-blind, placebo-controlled trial.

Setting: Thirty study centers in Canada and the U.S.

Synopsis: Two hundred patients with laboratory documented CDI on standard therapy with either metronidazole or vancomycin were randomized to receive a single IV infusion of combined monoclonal antibodies against CDA1 and CDB1 (n=101) or a normal saline placebo infusion (n=99). Patients were followed for 84 days with daily stool counts and intermittent blood samples for immunogenicity analysis.

The primary endpoint of recurrence of laboratory-proven C. diff diarrhea was significantly lower in the monoclonal antibody group (7% vs. 25% in placebo. 95% CI, 7-29; P <0.001). In a subgroup analysis of the epidemic BI/NAP1/027 strain, this favorable association persisted (8% vs. 32%). Recurrence in the antibody group was seen more in elderly patients hospitalized with a higher severity of underlying disease.

Secondary endpoints relating to the initial episode of CDI including treatment failure, severity of diarrhea, and duration to resolution were not significantly different between the two groups. Fewer accounts of serious adverse events were documented in the antibody group (18 patients vs. 28 patients in placebo, P=0.09), and immunogenicity was not detected in any patient.

Bottom line: Monoclonal antibody infusion against C. diff toxins reduces recurrence of infection, even with a hypervirulent (B1/NAP1/027) strain, without any significant adverse events.

Citation: Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010; 362(3):197-205. TH

PEDIATRIC HM LITERATURE

By Mark Shen, MD

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

Rectal Colonization with S. aureus Associated with Skin Abscesses

Clinical question: Is rectal colonization with Staphylococcus aureus more strongly associated with staphylococcal skin abscesses than nasal colonization?

Background: Staphylococcal skin and soft tissue infections have dramatically increased in recent years. While increased rates of nasal colonization with S. aureus have also been noted, a strong association with skin infections in children has not been established. The relationship between staphylococcal colonization of other body sites and skin infection is unknown.

Study design: Prospective cohort study.

Setting: Tertiary-care hospital in Buffalo, N.Y.

Synopsis: Sixty children, 0 to 18 years of age, requiring surgical drainage of S. aureus skin abscesses and 90 children undergoing other surgical procedures were enrolled consecutively. Rectal, nasal, and abscess (if applicable) cultures were obtained on all patients. Enrollment ceased when notably different rates of rectal colonization were recorded.

Rectal cultures were significantly more likely to be positive in the abscess group than the control group (47% vs. 1%; P<0.0001), while rates of nasal colonization were similar (27% vs. 21%; P=0.44). Abscess isolates were identical to rectal isolates in 88% of cases and nasal isolates in 75% of cases.

Other findings included a 60% prevalence of methicillin-resistant S. aureus (MRSA) in the abscess group. Fifty-nine of the 60 abscess isolates contained Panton-Valentine leukocidin genes; 57 were pulsed-field type USA300; and all 60 contained the staphylococcal cassette chromosome mec type IVa.

Given this representative sample of community-associated staphylococcal disease, these findings suggest that a focus on nasal carriage of S. aureus might be misguided.

Bottom Line: Rectal colonization with S. aureus better predicts skin abscess isolate than nasal carriage.

Citation: Faden H, Lesse AJ, Trask J, et al. Importance of colonization site in the current epidemic of staphylococcal skin abscesses. Pediatrics. 2010;125(3):e618-e624.