In the Literature: HM-Related Research You Need to Know


In This Edition

Literature at a Glance

A guide to this month’s studies


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.

Clinical Short


Cross-sectional cohort study shows new prescriptions, asthma medications, and those with copayments or delivered electronically are more frequently abandoned than opioids, antiplatelet medications, prescriptions without copayments, and those prescriptions not electronically transmitted.

Citation: Shrank WH, Choudhry NK, Fischer MA, et al. The epidemiology of prescriptions abandoned at the pharmacy. Ann Intern Med. 2010;153(10):633-640.


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.

Clinical Shorts


Voluntary responses from students in seven U.S. medical schools indicate that burnout is more associated with unprofessional and less-altruistic behaviors than is depression.

Citation: Dyrbye LN, Massie FS Jr, Eacker A, et al. Relationship between burnout and professional conduct and attitudes among US medical students. JAMA. 2010;304(11):1173-1180.


Invasive dental treatment might be associated with a transient increase in the risk for stroke and myocardial infarction in the first four weeks after the procedure. However, the short-lived risk is likely to be outweighed by long-term benefits of good dental health on vascular events.

Citation: Minassian C, D’Aiuto F, Hingorani AD, Smeeth L. Invasive dental treatment and risk for vascular events. Ann Intern Med. 2010;153:499-506.


Despite well-publicized guidelines, rates of venous thromboembolism prophylaxis remain substantially below Joint Commission targets.

Citation: Rothberg M, Lahti M, Pekow P, Lindenauer PK. Venous thromboembolism prophylaxis among medical patients at US hospitals. J Gen Intern Med. 2010;25(6):489-494.


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.