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In the Literature

From: The Hospitalist, June 2009

The latest research you need to know

by By Mital Patel, MD; Alraies Chadi, MD; Saurabh Kandpal, MD; Iqbal Masood, MD; Anuradha Ramaswamy, MD

Literature at a Glance

A guide to this month’s studies

Clinical Shorts


In the ATHENA trial, dronedarone decreased rates of first hospitalization due to cardiovascular events and death (31.9% vs. 39.4%) in atrial fibrillation without increasing pulmonary or thyroid toxicity.

Citation: Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.


CDC analysis from 1997-2007 reveals a 49.6% decrease in the actual incidence of MRSA central-line-associated BSI but a 25.8% increase in the proportion of MRSA in comparison with MSSA.

Citation: Burton DC, Edwards JR, Horan TC, Jernigan JA, Fridkin SK. Methicillin-resistant Staphylococcus aureus central line-associated bloodstream infections in US intensive care units, 1997-2007. JAMA. 2009;301(7):727-736.


Large cohort study fails to explain the rationale for widespread multivitamin use, because long-term use did not significantly impact risk for common cancers, cardiovascular disease, or mortality.

Citation: Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al. Multivitamin use and risk of cancer and cardiovascular disease in the Women’s Health Initiative cohorts. Arch Intern Med. 2009;169(3):294-304.


In this case-control study, fluconazole and linezolid were coined as independent risk factors for subsequent fluconazole-resistant Candida glabrata BSI, while cefepime and metronidazole increased the risk for susceptible glabrata BSI.

Citation: Lee I, Fishman NO, Zaoutis TE, et al. Risk factors for fluconazole-resistant Candida glabrata bloodstream infections. Arch Intern Med. 2009;169(4):379-383.


Multicenter study reveals that clinical risk stratification in non-ST elevation myocardial infarction (NSTEMI) conflicted with objective cardiac risk scores, was uninfluenced by prognosticators like heart failure and creatinine, and perpetuated under-recognition of risk.

Citation: Yan AT, Yan RT, Huynh T, et al. Understanding physicians’ risk stratification of acute coronary syndromes: insights from the Canadian ACS 2 Registry. Arch Intern Med. 2009;169(4):372-378.


In a blinded interventional study, hospitalists’ training in basic echocardiography improved assessment of lower ventricular dysfunction (46% to 59%), cardiomegaly, and pericardial effusions, but not valvular lesions.

Citation: Martin LD, Howell EE, Ziegelstein RC, et al. Hand-carried ultrasound performed by hospitalists: does it improve the cardiac physical examination? Am J Med. 2009;122(1):35-41.


Randomized controlled trial of 811 patients showed that reduced-calorie diets with different macronutrient compositions promoted clinically significant and similar weight loss. Weight loss was strongly predicted by group-

session attendance.

Citation: Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360(9):859-873.


In a prospective survey, patient (age, race, education) and system level (teaching service) factors influenced correct physician identification; those who could not were more likely to be unsatisfied with their care.

Citation: Arora V, Gangireddy S, Mehrotra A, Ginde R, Tormey M, Meltzer D. Ability of hospitalized patients to identify their in-hospital physicians. Arch Intern Med. 2009;169(2):199-201.

Inhaled Corticosteroid Use in COPD Associated with Increased Pneumonia Risk

Clinical question: Does long-term use of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD) increase the risk of developing pneumonia?

Background: Guidelines recommend a combination of inhaled corticosteroids and long-acting bronchodilators in patients with severe COPD. However, recent evidence has raised concerns about the increased risk of pneumonia in patients on inhaled steroids. The exact nature of this association and its specificity to the inhaled corticosteroid component is unclear.

Study design: Meta-analysis and systematic review of 18 randomized controlled trials (RCTs) evaluating inhaled corticosteroid use in COPD.

Setting: Medline, EMBASE, the Cochrane Database of Systematic Reviews, regulatory documents, and trial registries.

Synopsis: This study, which totaled 16,996 case reviews, focused on inhaled corticosteroid use in COPD (excluding asthma) with at least 24 weeks of followup. The study authors evaluated inhaled corticosteroid use—alone or in combination with long-acting beta-agonists (LABA)—against a control (placebo or LABA alone). Primary outcomes were any pneumonia and serious pneumonia leading to increased morbidity and mortality. Secondary outcomes included pneumonia-related mortality and all-cause mortality.

Inhaled corticosteroids—irrespective of associated LABA use—significantly increased the risk of pneumonia (7.4% vs. 4.7%) with a relative risk (RR) of 1.60; 95% CI, 1.33-1.92, P<0.001. Inhaled corticosteroids were strongly associated with an increase in serious pneumonia (RR 1.71; 95% CI, 1.46-1.99, P<0.001). However, inhaled corticosteroid use did not translate to significantly increased pneumonia-related or overall mortality, possibly due to the inadequate power of most of the individual trials.

The findings reflect those from other database studies, but lend specificity to the inhaled corticosteroid component. This can be cause for concern as studies of long-term inhaled corticosteroid use in patients with COPD have failed to show a benefit in mortality or decreased exacerbations.

Bottom line: Risk-benefit analysis for inhaled corticosteroid use in COPD patients should consider the increased risk of pneumonia, possibly related to local immunosuppression.

Citation: Singh S, Amin AV, Loke YK. Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease: a meta-analysis. Arch Intern Med. 2009;169(3):219-229.

Inadequate Physician Communication Regarding Dietary Supplement Usage

Clinical question: How frequently do hospital physicians communicate about the use of dietary supplements?

Background: About 20% of the U.S. population uses dietary supplements, products that have potential interactions with other prescription medications. Dietary supplement usage patterns, disclosure, and discussion with physicians have been studied in the outpatient setting. However, these metrics have not been evaluated in the inpatient setting.

Study design: A cross-sectional, observational pilot study.

Setting: Inpatients on a general medicine and geriatrics service at the University of North Carolina Medical Center.

Synopsis: Sixty inpatients were questioned regarding their use of dietary supplements in the past year. Patients were asked about their communication with the admitting resident physician regarding dietary supplements and their beliefs regarding continued use during hospitalization. Patient responses revealed prevalent dietary supplement use, with about 80% of patients using supplements and 52% using nonvitamin/nonmineral supplements.

The study revealed poor communication between residents and their patients. Only 20% of residents inquired about dietary supplement use during the admission process, while 74% of patients neglected to disclose their use of dietary supplements. Furthermore, 56% of patients thought communication was unimportant; they assumed that it was in their medical records (18%), or they expected the physician to ask them about it (20%). Though most patients agreed to stop using dietary supplements as inpatients, 13% did not think dietary supplement use was a problem, even if it went against medical advice.

Study limitations include the small sample size and recall bias inherent to the design. It also is likely that more patients using dietary supplements consented for the study, as evidenced by higher prevalence of use.

Bottom line: Use of dietary supplements in hospitalized patients is common, and communication about their use between patients and physicians is limited.

Citation: Young LA, Faurot KR, Gaylord SA. Use of and communication about dietary supplements among hospitalized patients. J Gen Intern Med. 2009;24(3):366-369.

Early Hyperglycemia Associated with Poor Outcomes After Acute Ischemic Stroke

Clinical question: Is there a threshold of hyperglycemia after an acute ischemic stroke (IS) that predicts a poor outcome?

Background: A growing body of evidence shows that admission hyperglycemia in an acute IS predicts a poor outcome. Current triggers to initiate glucose control measures are based on consensus data. However, capillary glucose is a continuous variable and could have a linear relationship with stroke outcomes. A particular glucose level may herald poor outcomes.

Study design: Prospective observational cohort study.

Setting: Seven university hospitals with dedicated stroke units in Spain.

Synopsis: 476 patients with acute IS had admission and maximum glucose levels recorded during the first 48 hours of admission. Stroke scales and brain imaging assessed the patients’ stroke severity. The primary endpoint of a poor outcome at three months was defined by a modified Rankin score of >2.

The primary endpoint was noted in 156 (38%) patients. Receiver operating characteristic curves for both capillary glucose at admission and maximal values within 48 hours pointed to 155mg/dL as a cutoff for the primary outcome. However, subsequent regression analysis confirmed only the maximal value as an independent predictor of poor outcome (OR 2.73; 95% CI, 1.42 to 5.24). Additionally, in contrast to patient age and infarct volume, the maximal glucose value of ≥155 mg/dL was associated with stroke severity on admission and a higher three-month mortality (HR 3.80; 95% CI, 1.79 to 8.10; P=0.001).

The observational nature of the study opens it to speculation: Does lowering the level to less than 155 mg/dl improve patient outcomes? However, it does offer a potential target for future interventional studies.

Bottom line: Hyperglycemia within the first 48 hours of an ischemic stroke offers a more robust predictor of poor outcomes compared with admission glucose levels. A glucose level less than 155 mg/dL could be a potential treatment goal in the future.

Citation: Fuentes B, Castillo J, San José B, et al. The prognostic value of capillary glucose levels in acute stroke: The GLycemia In Acute Stroke (GLIAS) study. Stroke. 2009;40(2):562-568.

Communication Between Inpatient Medical Teams and PCPs Does Not Improve Outcomes

Clinical question: Does communication between patients’ physicians in the hospital and their primary-care physicians (PCPs) improve outcomes after discharge?

Background: The increased use of the hospitalist model has resulted in concerns about discontinuity of patient care after discharge. This might hamper the quality of clinical care and increase adverse outcomes, including readmission or death. Effective communication could have the potential to improve clinical outcomes.

Study design: Survey based in a quasi-randomized cohort of medical inpatients.

Setting: Six academic medical centers throughout the U.S.

Synopsis: Of the initial 2,526 patients, only 1,078 were available for final analysis based on failure of patient followup and a 68% PCP response rate. PCP surveys were faxed two weeks after patient discharge. PCPs were asked about hospitalization awareness and communication methods. Patients were contacted post-discharge, and National Death Index data were reviewed to determine the primary composite outcomes of ED visits, hospital readmissions, or death at 30 days.

Four out of five PCPs surveyed were aware of their patients’ hospitalizations—23% via direct communication and 42% by discharge summary. The primary outcome occurred in 184 (22%) of 834 patients. In contrast, of the 244 PCPs unaware of their patients’ hospitalizations, the primary outcome occurred in 49 (20%) patients. After logistic regression, PCP awareness of hospitalization, irrespective of communication method, was not associated with risk of outcomes (adjusted OR 1.08, 95% CI, 0.73 to 1.59). Having a hospitalist as the hospital physician (34%) did not affect outcomes. These results could reflect the inclusion of patients with fewer comorbidities. Additionally, effect on adverse drug events, patient satisfaction, and quality of life were not evaluated.

Bottom line: Communication between inpatient physicians and PCPs needs improvement to affect clinical outcomes, especially in high-risk patients.

Citation: Bell CM, Schnipper JL, Auerbach AD, et al. Association of communication between hospital-based physicians and primary care providers with patient outcomes. J Gen Intern Med. 2008;24(3):381-386.

Gentamicin Use in Staphylococcal Bacteremia or Endocarditis Causes Nephrotoxicity

Clinical question: Does gentamicin synergism in Staphylococcal bacteremia and endocarditis achieve faster eradication at the cost of nephrotoxicity?

Background: Gentamicin has been used to help with sterilization of blood or cardiac vegetations in patients with Staphylococcal bacteremia or infective endocarditis (IE). However, historic data negate its role in decreasing morbidity or mortality. If its potential nephrotoxicity were better characterized, it could help assess the overall utility of this practice.

Study design: Retrospective analysis of a cohort from a published randomized control trial.

Setting: 44 hospitals in the U.S. and Europe.

Synopsis: Two hundred thirty-six patients with Staphylococcal bacteremia or native-valve IE (mostly right-sided) were randomized to receive standard therapy (vancomycin or antistaphylococcal penicillin) or daptomycin. Patients receiving standard therapy and those with left-side IE in the daptomycin arm also received low-dose gentamicin. Sequential creatinine levels were used to determine primary outcomes of renal impairment events and a decrease in creatinine clearance.

Renal impairment events, elevation of mean serum creatinine, and decrease in creatinine clearance were more prevalent with standard therapy, especially in the elderly and those with diabetes. Combination of gentamicin with penicillin caused an earlier creatinine elevation compared with that with vancomycin.

Patients on gentamicin had a modest decrease in creatinine clearance (22% vs. 8%; P= 0.005), especially if their baseline was 50 to 80 mL/min. The decrease was early and sustained with gentamicin exposure. Multivariate analysis revealed age (≥65 years) and gentamicin use (not dose and duration) to be independent predictors of renal impairment. The analysis fails to address use of gentamicin in prosthetic-valve IE and left-side IE.

Bottom line: Initial low-dose gentamicin use in Staphylococcal bacteremia or endocarditis increases nephrotoxicity with no clear mortality benefit.

Citation: Cosgrove SE, Vigliani GA, Fowler VG, et al. Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis. 2009;48(6):713-721.

Osteoporotic Fractures Increase Five-Year Mortality, Especially in the Elderly

Clinical question: What is the effect of initial osteoporotic fractures and subsequent fractures on mortality?

Background: With an aging population, osteoporotic fractures are poised to escalate into a national healthcare problem. Studies have outlined the increase in premature and long-term mortality associated with hip or vertebral fractures. However, other appendicular fractures have not been studied, and little is known about the mortality risk with subsequent fracturing.

Study design: Prospective cohort from the Dubbo Osteoporosis Epidemiology Study, a longitudinal, population-based study.

Setting: Stable population of men and women 60 and older in Dubbo, Australia.

Synopsis: 1,300 people with at least one minimal-trauma fracture were selected. Fractures were grouped as hip, vertebral, major (long bones and ribs), and minor (any remaining). Mortality data were extracted from local media, along with state and national registries. Age- and sex-specific mortality rates in each group were compared with population mortality rates to provide standardized mortality ratios (SMRs) over five-year periods.

Osteoporotic fractures increased five-year mortality with SMRs of 1.38 to 2.53 for women and 1.64 to 3.52 for men. An exception was minor fractures in patients 60 to 75 years old with no increase in mortality. Only hip fractures influenced mortality adversely for up to 10 years.

Interestingly, the nonhip, nonvertebral group included 50% of the fractures and contributed to 29% of overall mortality. Another five-year increase in mortality was evident in 364 people with a subsequent fracture.

A subgroup analysis revealed independent predictors of mortality, including lower bone mineral density, weaker quadriceps, smoking history, and increased sway in female patients; weaker quadriceps and decreased activities were independent predictors in male patients. Apart from the limitation that most subjects were white, the study gives a robust mortality analysis on osteoporotic fractures.

Bottom line: Osteoporotic fractures, initial and subsequent, increase five-year mortality. This is true even for nonhip, nonvertebral fractures, especially in the elderly.

Citation: Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301(5): 513-521.

Early Rehospitalization After Pulmonary Embolism Dictated by Clinical Severity and Anticoagulation Practices

Clinical question: What factors portend readmission after acute pulmonary embolism (PE)?

Background: The significant clinical and economic burden of acute pulmonary embolism (PE) has fueled studies to define predictors of early mortality. However, the variables leading to readmission after PE remain uncharted. Knowledge of these factors can provide additional targets to improve the quality of care.

Study design: Prospective population-based cohort study.

Setting: 186 acute-care hospitals in Pennsylvania.

Synopsis: Using ICD-9-CM codes, 14,426 PE patients were selected for the study. Primary outcome was hospital readmission within 30 days; secondary outcomes were venous thromboembolism (VTE) and bleeding.

More than 2,000 patients (14.3%) experienced a 30-day readmission. The predominant reasons were VTE (21.9%) and bleeding (5%), with the rest related to comorbidities, such as cancer (10.8%), pneumonia (5.2%), and chest pain (5.0%).

The discrete proportional odds model showed a significant association of high PE Severity Index score (OR 2.04; 95% CI, 1.73-2.40) and previous home care provision (OR 1.40; 95% CI, 1.27-1.54) with readmission, indicating that sicker patients tend to be readmitted. Black patients and Medicaid recipients were more likely to be readmitted, especially for VTE, which reflects the possible socioeconomic bearing on outcomes. Surprisingly, the few patients leaving the hospital against medical advice (0.4%) had a high OR of 2.84 (95% CI, 1.80-4.48) for readmission. Academic centers were not associated with increased readmissions but had significantly more readmissions for bleeding.

Anticoagulation practices—initial choice of agents, intensity of treatment, and monitoring—were not evaluated, which could affect readmission after PE, especially due to VTE and bleeding.

Bottom line: Apart from severity of illness and demographics, high rates of readmission after PE, especially for bleeding and VTE, might be related to poor anticoagulation practices.

Citation: Aujesky D, Mor MK, Geng M, Stone RA, Fine MJ, Ibrahim SA. Predictors of early hospital readmission after acute pulmonary embolism. Arch Intern Med. 2009;169(3):287-293.

Need for Improved Awareness of Hospital Readmission

Clinical question: What is the frequency of readmission awareness in discharging physicians and the trends in their communications with readmitting physicians?

Background: Rotation-based schedules of inpatient physicians, especially at academic centers, increase the likelihood that patients with complex medical or psychosocial issues requiring readmission will be cared for by a different team.

Though gaps in communication between the successive teams have the potential to hamper the quality of care, these gaps have not been adequately characterized in the literature.

Study design: Prospective cohort study.

Setting: Inpatient general-medicine services at two academic medical centers.

Synopsis: Researchers selected 225 patients readmitted within two weeks. The discharge and readmission teams were surveyed by e-mail within 48 hours of readmission regarding frequency and content of communications.

On analysis, the discharging teams were aware of patient readmissions only 48.5% of the time. Most of the remaining teams acknowledged a desire to be notified.

Actual communication occurred in 43.7% of cases and included information on medical assessments (61.9%), psychosocial issues (52.9%), pending tests (34%), and discharge medications (30.9%).

As expected, physician perception of higher medical complexity increased the likelihood of communication. Surprisingly, though psychosocial issues did not predict communication, they were discussed in almost half the cases. Lapses in communication were attributed to lack of time, perceived necessity, and contact information.

The observational nature, nongeneralizable population, and effect of responder bias limit the study. Though an interventional study can better evaluate improvement in patient outcomes, communication at readmission can be used as an educational feedback tool for house staff and attendings.

Bottom line: Modest frequency of communication between discharge and readmission physicians is driven mostly by medical complexity. It bears the potential to improve patient outcomes and offer valuable feedback.

Citation: Roy CL, Kachalia A, Woolf S, Burdick E, Karson A, Gandhi TK. Hospital readmissions: physician awareness and communication practices. J Gen Intern Med. 2009;24(3):374–380. TH

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