Rubin Bahuva, MD

Clinical question: Can the aortic dissection detection (ADD) risk score be used to screen patients for acute aortic dissection at the bedside?

Background: AAD, a life-threatening condition, often is missed due to relatively low incidence, varied presentation, and need for advanced imaging studies. The American Heart Association and the American College of Cardiology have published guidelines on thoracic aortic disease from which the ADD risk score has been adapted to identify high-risk patients and to suggest additional testing based on pretest probability of disease.

Study design: Retrospective application of ADD risk score to the International Registry of Acute Aortic Dissection (IRAD) database.

Setting: Multinational medical registry compiled from 24 medical centers.

Synopsis: A total of 2,538 patients with confirmed ADD were reviewed. The number of patients presenting with one or more of 12 proposed clinical risk markers was determined. An ADD risk score of 0 to 3 was calculated based on the number of risk categories (high-risk predisposing conditions, pain features, examination features) in which patients met criteria.

Among 108 (4.3%) patients found to be low-risk (ADD score 0), 72 had a chest X-ray, 35 of which were found to have a widened mediastinum. High-risk features (ADD score 2 or 3) were found in 1,503 (59.2%) patients, and the remaining 927 (36.5%) patients had intermediate risk (ADD score 1).

The guidelines recommend further imaging for all intermediate- and high-risk patients and for low-risk patients with a wide mediastinum resulting in very good sensitivity.

Bottom line: The ADD risk score is a sensitive bedside screening tool for aortic dissection, ensuring that more than 95% patients with true dissection undergo further investigation, but it may lead to overinvestigation due to unknown specificity.

Citation: Rogers AM, Hermann LK, Booher AM, et al. Sensitivity of the aortic dissection detection risk score, a novel guideline-based tool for identification of acute aortic dissection at initial presentation: results from the international registry of acute aortic dissection. Circ. 2011;123:2213-2218.

For more physician reviews of HM-related literature, visit our website and search "Literature."

Clinical question: Can the aortic dissection detection (ADD) risk score be used to screen patients for acute aortic dissection at the bedside?

Background: AAD, a life-threatening condition, often is missed due to relatively low incidence, varied presentation, and need for advanced imaging studies. The American Heart Association and the American College of Cardiology have published guidelines on thoracic aortic disease from which the ADD risk score has been adapted to identify high-risk patients and to suggest additional testing based on pretest probability of disease.

Study design: Retrospective application of ADD risk score to the International Registry of Acute Aortic Dissection (IRAD) database.

Setting: Multinational medical registry compiled from 24 medical centers.

Synopsis: A total of 2,538 patients with confirmed ADD were reviewed. The number of patients presenting with one or more of 12 proposed clinical risk markers was determined. An ADD risk score of 0 to 3 was calculated based on the number of risk categories (high-risk predisposing conditions, pain features, examination features) in which patients met criteria.

Among 108 (4.3%) patients found to be low-risk (ADD score 0), 72 had a chest X-ray, 35 of which were found to have a widened mediastinum. High-risk features (ADD score 2 or 3) were found in 1,503 (59.2%) patients, and the remaining 927 (36.5%) patients had intermediate risk (ADD score 1).

The guidelines recommend further imaging for all intermediate- and high-risk patients and for low-risk patients with a wide mediastinum resulting in very good sensitivity.

Bottom line: The ADD risk score is a sensitive bedside screening tool for aortic dissection, ensuring that more than 95% patients with true dissection undergo further investigation, but it may lead to overinvestigation due to unknown specificity.

Citation: Rogers AM, Hermann LK, Booher AM, et al. Sensitivity of the aortic dissection detection risk score, a novel guideline-based tool for identification of acute aortic dissection at initial presentation: results from the international registry of acute aortic dissection. Circ. 2011;123:2213-2218.

For more physician reviews of HM-related literature, visit our website and search "Literature."

Clinical question: Can the aortic dissection detection (ADD) risk score be used to screen patients for acute aortic dissection at the bedside?

Background: AAD, a life-threatening condition, often is missed due to relatively low incidence, varied presentation, and need for advanced imaging studies. The American Heart Association and the American College of Cardiology have published guidelines on thoracic aortic disease from which the ADD risk score has been adapted to identify high-risk patients and to suggest additional testing based on pretest probability of disease.

Study design: Retrospective application of ADD risk score to the International Registry of Acute Aortic Dissection (IRAD) database.

Setting: Multinational medical registry compiled from 24 medical centers.

Synopsis: A total of 2,538 patients with confirmed ADD were reviewed. The number of patients presenting with one or more of 12 proposed clinical risk markers was determined. An ADD risk score of 0 to 3 was calculated based on the number of risk categories (high-risk predisposing conditions, pain features, examination features) in which patients met criteria.

Among 108 (4.3%) patients found to be low-risk (ADD score 0), 72 had a chest X-ray, 35 of which were found to have a widened mediastinum. High-risk features (ADD score 2 or 3) were found in 1,503 (59.2%) patients, and the remaining 927 (36.5%) patients had intermediate risk (ADD score 1).

The guidelines recommend further imaging for all intermediate- and high-risk patients and for low-risk patients with a wide mediastinum resulting in very good sensitivity.

Bottom line: The ADD risk score is a sensitive bedside screening tool for aortic dissection, ensuring that more than 95% patients with true dissection undergo further investigation, but it may lead to overinvestigation due to unknown specificity.

Citation: Rogers AM, Hermann LK, Booher AM, et al. Sensitivity of the aortic dissection detection risk score, a novel guideline-based tool for identification of acute aortic dissection at initial presentation: results from the international registry of acute aortic dissection. Circ. 2011;123:2213-2218.

For more physician reviews of HM-related literature, visit our website and search "Literature."

Clinical question: In patients with candidemia, what are the incidence, risk factors, and antifungal treatment outcomes for ocular candidiasis?

Background: The incidence and treatment outcomes of ocular candidiasis have not been studied extensively.

Study design: Randomized noninferiority trial.

Setting: Multicenter study of 370 patients.

Synopsis: This study randomized 370 non-neutropenic patients with candidemia in a 2:1 ratio to receive voriconazole monotherapy or amphotericin B followed by fluconazole. Patients were treated for at least two weeks after the last positive blood culture, for a maximum duration of eight weeks. Baseline and follow-up fundoscopic examinations were performed.

Sixty (16%) patients were diagnosed with ocular candidiasis, of which six (1.6%) were diagnosed with endophthalmitis and 34 (9%) with chorioretinitis. Patients with ocular candidiasis had a longer duration of candidemia, and were more likely to be infected with Candida albicans.

Outcomes were not available in 19 patients with ocular candidiasis due to death or loss of follow-up. There was no significant difference between the cure rate of voriconazole (93.5% [29/31]), compared with the amphotericin B group (100% [10/10]).

Bottom line: Ocular candidiasis occurs in approximately 16% of non-neutropenic patients with candidemia. A longer duration of candidemia and infection with C. albicans were associated with ocular candidiasis. Both voriconazole and amphotericin B/fluconazole are effective in patients with ocular candidiasis.

Citation: Oude Lashof AM, Rothova A, Sobel JD, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53:262-268.

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

Clinical question: In patients with candidemia, what are the incidence, risk factors, and antifungal treatment outcomes for ocular candidiasis?

Background: The incidence and treatment outcomes of ocular candidiasis have not been studied extensively.

Study design: Randomized noninferiority trial.

Setting: Multicenter study of 370 patients.

Synopsis: This study randomized 370 non-neutropenic patients with candidemia in a 2:1 ratio to receive voriconazole monotherapy or amphotericin B followed by fluconazole. Patients were treated for at least two weeks after the last positive blood culture, for a maximum duration of eight weeks. Baseline and follow-up fundoscopic examinations were performed.

Sixty (16%) patients were diagnosed with ocular candidiasis, of which six (1.6%) were diagnosed with endophthalmitis and 34 (9%) with chorioretinitis. Patients with ocular candidiasis had a longer duration of candidemia, and were more likely to be infected with Candida albicans.

Outcomes were not available in 19 patients with ocular candidiasis due to death or loss of follow-up. There was no significant difference between the cure rate of voriconazole (93.5% [29/31]), compared with the amphotericin B group (100% [10/10]).

Bottom line: Ocular candidiasis occurs in approximately 16% of non-neutropenic patients with candidemia. A longer duration of candidemia and infection with C. albicans were associated with ocular candidiasis. Both voriconazole and amphotericin B/fluconazole are effective in patients with ocular candidiasis.

Citation: Oude Lashof AM, Rothova A, Sobel JD, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53:262-268.

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

Clinical question: In patients with candidemia, what are the incidence, risk factors, and antifungal treatment outcomes for ocular candidiasis?

Background: The incidence and treatment outcomes of ocular candidiasis have not been studied extensively.

Study design: Randomized noninferiority trial.

Setting: Multicenter study of 370 patients.

Synopsis: This study randomized 370 non-neutropenic patients with candidemia in a 2:1 ratio to receive voriconazole monotherapy or amphotericin B followed by fluconazole. Patients were treated for at least two weeks after the last positive blood culture, for a maximum duration of eight weeks. Baseline and follow-up fundoscopic examinations were performed.

Sixty (16%) patients were diagnosed with ocular candidiasis, of which six (1.6%) were diagnosed with endophthalmitis and 34 (9%) with chorioretinitis. Patients with ocular candidiasis had a longer duration of candidemia, and were more likely to be infected with Candida albicans.

Outcomes were not available in 19 patients with ocular candidiasis due to death or loss of follow-up. There was no significant difference between the cure rate of voriconazole (93.5% [29/31]), compared with the amphotericin B group (100% [10/10]).

Bottom line: Ocular candidiasis occurs in approximately 16% of non-neutropenic patients with candidemia. A longer duration of candidemia and infection with C. albicans were associated with ocular candidiasis. Both voriconazole and amphotericin B/fluconazole are effective in patients with ocular candidiasis.

Citation: Oude Lashof AM, Rothova A, Sobel JD, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53:262-268.

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

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Atelectasis and fever
2. Heparin dosing frequency for VTE prophylaxis
3. Perioperative cardiac risk calculator
4. Diagnosing subarachnoid hemorrhage without an LP
5. Model to predict risk of bleeding on warfarin
6. Risk of death with tiotropium use in COPD
7. BNP to predict perioperative mortality
8. Beta-blockers and COPD

No Association Found between Atelectasis and Early Postopera-tive Fever

Clinical question: Is atelectasis really a major cause of early (up to 48 hours) postoperative fever (EPF)?

Background: Both fever and atelectasis are common findings in the postoperative period. EPF is believed to be noninfectious, and many textbooks consider atelectasis to be the most common cause. However, this association is controversial with no clear evidence.

Study design: Systematic review of prospective studies evaluating atelectasis and postoperative fever using PubMed and Scopus databases.

Setting: Postoperative patients (predominantly cardiac, maxillofacial, and abdominal surgeries). Lung surgery patients were excluded.

Synopsis: Eight prospective studies (four interventional and four observational) with 998 patients were included for review. All studies diagnosed atelectasis based on chest imaging but only three studies used the conventional definition of ≥38°C for fever. Seven studies individually reported no association between atelectasis and EPF.

Only five studies had eligible data for pooling and analysis. EPF was found to be a very weak indicator (diagnostic OR 1.4; 95% CI 0.92-2.12) of atelectasis. EPF also fared poorly for ruling out (sensitivity 13% to 47%) or ruling in (specificity 41% to 87%) the diagnosis of atelectasis with similarly poor positive and negative predictive values.

The results of this study, however, should be interpreted with caution. It was not a formal meta-analysis, due to the heterogeneity of the studies included with regard to the definition of fever, time points of imaging, and the variation of end points.

Bottom line: Since there is no clinical evidence to prove an association between atelectasis and fever, it is presumed that atelectasis may not be a cause of EPF.

Citation: Mavros MN, Velmahos GC, Falagas ME. Atelectasis as a cause of postoperative fever: where is the clinical evidence? Chest. 2011;140:418-424.

Unfractionated Heparin Can be Given Either BID or TID for Throm-boprophylaxis

Clinical question: Which is the best dosing frequency of unfractionated heparin (UFH) in preventing venous thromboembolism?

Background: Low-dose UFH is commonly used in hospitals for pharmacologic prophylaxis against venous thromboembolism. However, the risks and benefits of BID vs. TID dosing are not clear.

Study design: Mixed-treatment comparison (MTC) meta-analysis of RCTs.

Setting: RCTs on thromboprophylaxis regimens, selected from two previous systematic reviews and an updated literature search.

Synopsis: Included in the analysis were 27,667 patients from 16 RCTs comparing three prophylactic regimens (UFH BID, UFH TID, or low-molecular-weight heparin) with each other or with controls. Stroke and some myocardial infarction patients were excluded. The outcomes measured were DVT, pulmonary embolism (PE), major bleeding, and death. As compared with controls, all three regimens significantly reduced DVT (ranging from 58% to 72%), showed a nonsignificant trend toward reduction in PE (by 46% to 67%), and had no difference in risk of major bleeding or death.

UFH BID vs. TID were compared indirectly by using data from their trials against control patients or low-molecular-weight heparin. There was no significant difference between UFH TID and BID in reducing DVT (RR 1.56, CI 0.64-4.33), PE (RR 1.67, CI 0.49-208.9), mortality (RR 1.17, CI 0.72-1.95), or causing major bleeding (RR 0.89, CI 0.08-7.05). Additionally, both UFH dosing frequencies were similar to low-molecular-weight heparin in all four measured outcomes. This evidence is of moderate quality due to the lack of a direct comparison between UFH BID vs. TID.

Bottom line: Both BID and TID dosing of UFH are acceptable thromboprophylaxis regimens in hospitalized medical patients with no difference in effect on DVT, PE, major bleeding, or death.

Citation: Phung OJ, Kahn SR, Cook DJ, et al. Dosing frequency of unfractionated heparin thromboprophylaxis: a meta-analysis. Chest. 2011;140: 374-381.

New Cardiac-Risk Calculator Improves Prediction of Intra-/Postoperative Myocardial Infarction and Cardiac Arrest

Clinical question: Can a more accurate risk calculator than the Revised Cardiac Risk Index (RCRI) be developed and validated to predict postoperative cardiac events?

Background: The majority of perioperative deaths are secondary to cardiac-related events. The RCRI is the most commonly used preoperative risk stratification tool, but it has limitations and low discriminatory ability.

Study design: Multicenter prospective National Surgical Quality Improvement Program database study.

Setting: More than 250 academic and community U.S. hospitals.

Synopsis: Data were obtained from patients over a two-year period (2007 and 2008). From the 2007 data set (n=211,410), perioperative myocardial infarction or cardiac arrest (MICA) was seen in 1,371 patients (0.65%). After multivariate analysis on the 2007 data set, five risk predictors were obtained (increasing age, American anesthesiology class, dependent functional status, abnormal serum creatinine of >1.5 mg/dL, and type of surgery). This was validated utilizing the 2008 data set (n=257,385), where MICA was seen in 1,401 patients (0.54%).

The risk-predictive model showed excellent discrimination (distinguishing between events and nonevents) after application of C statistics to the dataset. The discriminatory ability was better when compared with the RCRI model. Limitations included nonavailability of information on preoperative stress test, arrhythmia, and aortic valve disease.

Bottom line: The new risk calculator model would help predict MICA more accurately, which in turn would help in preoperative optimization and patient counseling.

Citation: Gupta PK, Gupta H, Sundaram A, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circ. 2011;124:381-387.

Third-Generation CT Scans are Very Sensitive in Detecting Subarachnoid Hemorrhage

Clinical question: Are modern third-generation CT scans good enough to exclude subarachnoid hemorrhage (SAH) without a lumbar puncture (LP)?

Background: SAH is a neurosurgical emergency identified in about 1% of patients with headache in the emergency department. As the standard of care, all patients with suspected SAH have to undergo LP if a CT scan of the brain is normal. However, LP causes pain and delays discharge from the emergency department.

Study design: Prospective multicenter cohort study.

Setting: Eleven tertiary-care Canadian emergency departments.

Synopsis: From November 2000 to December 2009, data on all alert patients (n=3,132) who presented with acute headache and underwent emergent head CT were collected. Of these, 240 had SAH (7.7%). The sensitivity of CT overall for detecting SAH was 92.9% and the specificity was 100%. For the 953 patients scanned within six hours of headache onset, all 121 patients with SAH were identified by CT, yielding a sensitivity of 100% and specificity of 100%.

The study was limited largely by the lack of a consensus definition on the diagnosis of SAH and by some patient enrollment issues in the emergency department. Overall, these findings should give clinicians more confidence in forgoing an LP in patients with a negative head CT if done within six hours of the onset of their headache.

Bottom line: Modern third-generation CT scans are extremely sensitive for SAH if performed within six hours of the headache onset and interpreted by a qualified radiologist, thus possibly excluding the need for an LP.

Citation: Perry JJ, Stiell IG, Sivilotti ML, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. Br Med J. 2011;343:d4277.

Improved Model Stratifies Risk of Warfarin-Associated Bleeding in Patients with Atrial Fibrillation

Clinical question: Can a simple scoring model accurately assess the risk of warfarin-associated bleeding in a cohort of patients with atrial fibrillation?

Background: It is well known that anticoagulants, such as warfarin, dramatically reduce the risk of thromboembolic events in patients with atrial fibrillation. Despite this, clinicians often find themselves weighing the risks and benefits of anticoagulation in this cohort of patients, and improved models to assess those risks are needed.

Study design: Retrospective cohort study.

Setting: Kaiser Permanente of Northern California.

Synopsis: From a cohort of 13,559 adult patients with atrial fibrillation, the investigators used chart review to determine hemorrhagic events in this population and developed a model using Cox regression to assess hemorrhagic risk in certain patient populations. Final input variables for the model included anemia, severe renal disease, age ≥75, prior hemorrhage, and hypertension. When collapsed into three risk tiers (low, intermediate, and high), the scoring model nicely differentiated low (<1% annual) from high (5.8% annual) bleeding risk.

This study is limited by the lack of information on concomitant use of NSAIDs or aspirin in these patients and the lack of external validation of the model. Despite those limitations, it may serve as a valuable tool for clinicians. As the number of alternatives to warfarin rise and as those agents become more familiar, it will become increasingly important to accurately assess hemorrhage risk with various anticoagulants.

Bottom line: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk scoring system is a reliable and easy way for clinicians to estimate the degree of bleeding risk in patients anticoagulated with warfarin for atrial fibrillation.

Citation: Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study. J Am Coll Cardiol. 2011;58:395-401.

Tiotropium Mist Inhaler Associated with Increased Mortality

Clinical question: Does the mist-inhaler formulation of tiotropium increase mortality in patients with chronic obstructive pulmonary disease (COPD) when compared with placebo?

Background: Tiotropium is used in patients with COPD to reduce both symptoms of dyspnea and exacerbations of COPD. Tiotropium comes in two formulations: a powder (approved in the U.S.) and the mist inhaler (not approved in the U.S. but approved in 55 other countries). There are concerns based on recent studies that tiotropium may increase cardiovascular events and death.

Study design: Meta-analysis of five randomized controlled trials (RCTs) comparing tiotropium mist inhaler with a placebo.

Setting: Multinational studies.

Synopsis: This study of 6,522 patients with COPD showed a 52% increased risk of all-cause mortality with the use of the tiotropium mist inhaler when compared with placebo. It is important to note that there are data showing higher plasma concentrations with the approved mist-inhaler doses when compared with the powder formulation doses. Further, a possible dose effect was seen in this study (though not statistically significant), with higher tiotropium doses associated with a high-risk ratio for the mortality endpoint.

Limitations of this study include the fact that the dosage of the tiotropium varied, as did the length of follow-up for patients. Given that death was a relatively rare event (<1%), estimates are imprecise. Even given these limitations, this study sheds light on the debate over the safety of tiotropium, specifically the mist-inhaler formulation. Caution should be used when prescribing the mist-inhaler formulation of tiotropium, and an understanding of the potential cardiovascular risks should be communicated to patients prior to initiating therapy.

Bottom line: This study shows that the mist-inhaler formulation of tiotropium is associated with an increased risk of cardiovascular mortality.

Citation: Singh S, Loke YK, Enright PL, Furnberg CD. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. Br Med J. 2011;342: d3215.

B-Type Natriuretic Peptide (BNP) Is an Independent Predictor of Cardiovascular Events in Patients Undergoing Vascular Surgery

Clinical question: Can preoperative natriuretic peptide levels be used to independently predict perioperative cardiovascular events in patients undergoing vascular surgery?

Background: Currently we use the type of surgery, exercise tolerance, and clinical risk factors to predict perioperative cardiovascular risk. Clinical risk factors, based on the Revised Cardiac Risk Index, or RCRI, include history of ischemic heart disease, heart failure, cerebrovascular events, diabetes mellitus, and renal insufficiency. Recent studies have shown that the pre-operative natriuretic peptides can independently predict perioperative cardiovascular events.

Study design: Individual patient meta-analysis.

Setting: Data sets obtained from six multinational studies.

Synopsis: This meta-analysis included datasets from five studies that used BNP (632 patients) and one study that used NT-proBNP (218 patients) to assess the postoperative cardiovascular events in patients undergoing vascular surgery. Patients with elevated BNP level are at a higher risk of cardiac death (OR 4.3, 95% CI: 1.7-11.3) and all-cause mortality (OR 3.1, 95% CI: 1.4-6.7) within 30 days of vascular surgery. When the RCRI-based groups were reclassified using natriuretic peptide level, the improvement in discrimination was statistically significant. Limitations of this study include: 1) Individual patient data was not obtained for all studies that met the search criteria; and 2) Different types of BNP assays were used in different studies included.

Bottom line: Preoperative BNP level is an independent predictor of cardiovascular events at 30 days after vascular surgery. The addition of preoperative BNP level improves the predictive performance of the RCRI score.

Citation: Rodseth RN, Lurati Buse GA, Bolliger D, et al. The predictive ability of pre-operative B-type natriuretic peptide in vascular patients for major adverse cardiac events: an individual patient data meta-analysis. J Am Coll Cardiol. 2011;58:522-529.

Beta-Blockers May be Beneficial in Patients with Chronic Obstructive Pulmonary Disease

Clinical question: Is it beneficial to use beta-blockers in patients with chronic obstructive pulmonary disease (COPD) if there is an indication?

Background: Patients with COPD may have concomitant cardiovascular disease, which may warrant use of beta-blockers. Many physicians are concerned about using beta-blockers in COPD patients due to the risk of bronchospasm. Evidence suggests that cardio-selective beta-blockers do not cause deterioration of pulmonary status in COPD patients. There is also growing evidence that beta-blockers may be beneficial in patients with COPD.

Study design: Retrospective cohort study.

Setting: Data obtained from a disease-specific (COPD) database in Scotland.

Synopsis: This study included 5,977 patients who were older than 50 and excluded patients with history of malignancy. Beta-blockers were associated with a 22% reduction in all-cause mortality. There was no significant difference between cardio-selective and nonselective beta-blockers. The benefits of beta-blockers in COPD patients were independent of history of cardiovascular disease. There was no significant decline in pulmonary function (FEV1) over time. Beta-blocker usage also reduced the number of hospital admissions for COPD exacerbation. These benefits were shown in patients using different type of inhalers.

Bottom line: In patients older than 50, beta-blockers may not only reduce COPD exacerbations and hospital admissions, but also reduce all-cause mortality without adversely affecting pulmonary function.

Citation: Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. Br Med J. 2011;342:d2549.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Atelectasis and fever
2. Heparin dosing frequency for VTE prophylaxis
3. Perioperative cardiac risk calculator
4. Diagnosing subarachnoid hemorrhage without an LP
5. Model to predict risk of bleeding on warfarin
6. Risk of death with tiotropium use in COPD
7. BNP to predict perioperative mortality
8. Beta-blockers and COPD

No Association Found between Atelectasis and Early Postopera-tive Fever

Clinical question: Is atelectasis really a major cause of early (up to 48 hours) postoperative fever (EPF)?

Background: Both fever and atelectasis are common findings in the postoperative period. EPF is believed to be noninfectious, and many textbooks consider atelectasis to be the most common cause. However, this association is controversial with no clear evidence.

Study design: Systematic review of prospective studies evaluating atelectasis and postoperative fever using PubMed and Scopus databases.

Setting: Postoperative patients (predominantly cardiac, maxillofacial, and abdominal surgeries). Lung surgery patients were excluded.

Synopsis: Eight prospective studies (four interventional and four observational) with 998 patients were included for review. All studies diagnosed atelectasis based on chest imaging but only three studies used the conventional definition of ≥38°C for fever. Seven studies individually reported no association between atelectasis and EPF.

Only five studies had eligible data for pooling and analysis. EPF was found to be a very weak indicator (diagnostic OR 1.4; 95% CI 0.92-2.12) of atelectasis. EPF also fared poorly for ruling out (sensitivity 13% to 47%) or ruling in (specificity 41% to 87%) the diagnosis of atelectasis with similarly poor positive and negative predictive values.

The results of this study, however, should be interpreted with caution. It was not a formal meta-analysis, due to the heterogeneity of the studies included with regard to the definition of fever, time points of imaging, and the variation of end points.

Bottom line: Since there is no clinical evidence to prove an association between atelectasis and fever, it is presumed that atelectasis may not be a cause of EPF.

Citation: Mavros MN, Velmahos GC, Falagas ME. Atelectasis as a cause of postoperative fever: where is the clinical evidence? Chest. 2011;140:418-424.

Unfractionated Heparin Can be Given Either BID or TID for Throm-boprophylaxis

Clinical question: Which is the best dosing frequency of unfractionated heparin (UFH) in preventing venous thromboembolism?

Background: Low-dose UFH is commonly used in hospitals for pharmacologic prophylaxis against venous thromboembolism. However, the risks and benefits of BID vs. TID dosing are not clear.

Study design: Mixed-treatment comparison (MTC) meta-analysis of RCTs.

Setting: RCTs on thromboprophylaxis regimens, selected from two previous systematic reviews and an updated literature search.

Synopsis: Included in the analysis were 27,667 patients from 16 RCTs comparing three prophylactic regimens (UFH BID, UFH TID, or low-molecular-weight heparin) with each other or with controls. Stroke and some myocardial infarction patients were excluded. The outcomes measured were DVT, pulmonary embolism (PE), major bleeding, and death. As compared with controls, all three regimens significantly reduced DVT (ranging from 58% to 72%), showed a nonsignificant trend toward reduction in PE (by 46% to 67%), and had no difference in risk of major bleeding or death.

UFH BID vs. TID were compared indirectly by using data from their trials against control patients or low-molecular-weight heparin. There was no significant difference between UFH TID and BID in reducing DVT (RR 1.56, CI 0.64-4.33), PE (RR 1.67, CI 0.49-208.9), mortality (RR 1.17, CI 0.72-1.95), or causing major bleeding (RR 0.89, CI 0.08-7.05). Additionally, both UFH dosing frequencies were similar to low-molecular-weight heparin in all four measured outcomes. This evidence is of moderate quality due to the lack of a direct comparison between UFH BID vs. TID.

Bottom line: Both BID and TID dosing of UFH are acceptable thromboprophylaxis regimens in hospitalized medical patients with no difference in effect on DVT, PE, major bleeding, or death.

Citation: Phung OJ, Kahn SR, Cook DJ, et al. Dosing frequency of unfractionated heparin thromboprophylaxis: a meta-analysis. Chest. 2011;140: 374-381.

New Cardiac-Risk Calculator Improves Prediction of Intra-/Postoperative Myocardial Infarction and Cardiac Arrest

Clinical question: Can a more accurate risk calculator than the Revised Cardiac Risk Index (RCRI) be developed and validated to predict postoperative cardiac events?

Background: The majority of perioperative deaths are secondary to cardiac-related events. The RCRI is the most commonly used preoperative risk stratification tool, but it has limitations and low discriminatory ability.

Study design: Multicenter prospective National Surgical Quality Improvement Program database study.

Setting: More than 250 academic and community U.S. hospitals.

Synopsis: Data were obtained from patients over a two-year period (2007 and 2008). From the 2007 data set (n=211,410), perioperative myocardial infarction or cardiac arrest (MICA) was seen in 1,371 patients (0.65%). After multivariate analysis on the 2007 data set, five risk predictors were obtained (increasing age, American anesthesiology class, dependent functional status, abnormal serum creatinine of >1.5 mg/dL, and type of surgery). This was validated utilizing the 2008 data set (n=257,385), where MICA was seen in 1,401 patients (0.54%).

The risk-predictive model showed excellent discrimination (distinguishing between events and nonevents) after application of C statistics to the dataset. The discriminatory ability was better when compared with the RCRI model. Limitations included nonavailability of information on preoperative stress test, arrhythmia, and aortic valve disease.

Bottom line: The new risk calculator model would help predict MICA more accurately, which in turn would help in preoperative optimization and patient counseling.

Citation: Gupta PK, Gupta H, Sundaram A, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circ. 2011;124:381-387.

Third-Generation CT Scans are Very Sensitive in Detecting Subarachnoid Hemorrhage

Clinical question: Are modern third-generation CT scans good enough to exclude subarachnoid hemorrhage (SAH) without a lumbar puncture (LP)?

Background: SAH is a neurosurgical emergency identified in about 1% of patients with headache in the emergency department. As the standard of care, all patients with suspected SAH have to undergo LP if a CT scan of the brain is normal. However, LP causes pain and delays discharge from the emergency department.

Study design: Prospective multicenter cohort study.

Setting: Eleven tertiary-care Canadian emergency departments.

Synopsis: From November 2000 to December 2009, data on all alert patients (n=3,132) who presented with acute headache and underwent emergent head CT were collected. Of these, 240 had SAH (7.7%). The sensitivity of CT overall for detecting SAH was 92.9% and the specificity was 100%. For the 953 patients scanned within six hours of headache onset, all 121 patients with SAH were identified by CT, yielding a sensitivity of 100% and specificity of 100%.

The study was limited largely by the lack of a consensus definition on the diagnosis of SAH and by some patient enrollment issues in the emergency department. Overall, these findings should give clinicians more confidence in forgoing an LP in patients with a negative head CT if done within six hours of the onset of their headache.

Bottom line: Modern third-generation CT scans are extremely sensitive for SAH if performed within six hours of the headache onset and interpreted by a qualified radiologist, thus possibly excluding the need for an LP.

Citation: Perry JJ, Stiell IG, Sivilotti ML, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. Br Med J. 2011;343:d4277.

Improved Model Stratifies Risk of Warfarin-Associated Bleeding in Patients with Atrial Fibrillation

Clinical question: Can a simple scoring model accurately assess the risk of warfarin-associated bleeding in a cohort of patients with atrial fibrillation?

Background: It is well known that anticoagulants, such as warfarin, dramatically reduce the risk of thromboembolic events in patients with atrial fibrillation. Despite this, clinicians often find themselves weighing the risks and benefits of anticoagulation in this cohort of patients, and improved models to assess those risks are needed.

Study design: Retrospective cohort study.

Setting: Kaiser Permanente of Northern California.

Synopsis: From a cohort of 13,559 adult patients with atrial fibrillation, the investigators used chart review to determine hemorrhagic events in this population and developed a model using Cox regression to assess hemorrhagic risk in certain patient populations. Final input variables for the model included anemia, severe renal disease, age ≥75, prior hemorrhage, and hypertension. When collapsed into three risk tiers (low, intermediate, and high), the scoring model nicely differentiated low (<1% annual) from high (5.8% annual) bleeding risk.

This study is limited by the lack of information on concomitant use of NSAIDs or aspirin in these patients and the lack of external validation of the model. Despite those limitations, it may serve as a valuable tool for clinicians. As the number of alternatives to warfarin rise and as those agents become more familiar, it will become increasingly important to accurately assess hemorrhage risk with various anticoagulants.

Bottom line: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk scoring system is a reliable and easy way for clinicians to estimate the degree of bleeding risk in patients anticoagulated with warfarin for atrial fibrillation.

Citation: Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study. J Am Coll Cardiol. 2011;58:395-401.

Tiotropium Mist Inhaler Associated with Increased Mortality

Clinical question: Does the mist-inhaler formulation of tiotropium increase mortality in patients with chronic obstructive pulmonary disease (COPD) when compared with placebo?

Background: Tiotropium is used in patients with COPD to reduce both symptoms of dyspnea and exacerbations of COPD. Tiotropium comes in two formulations: a powder (approved in the U.S.) and the mist inhaler (not approved in the U.S. but approved in 55 other countries). There are concerns based on recent studies that tiotropium may increase cardiovascular events and death.

Study design: Meta-analysis of five randomized controlled trials (RCTs) comparing tiotropium mist inhaler with a placebo.

Setting: Multinational studies.

Synopsis: This study of 6,522 patients with COPD showed a 52% increased risk of all-cause mortality with the use of the tiotropium mist inhaler when compared with placebo. It is important to note that there are data showing higher plasma concentrations with the approved mist-inhaler doses when compared with the powder formulation doses. Further, a possible dose effect was seen in this study (though not statistically significant), with higher tiotropium doses associated with a high-risk ratio for the mortality endpoint.

Limitations of this study include the fact that the dosage of the tiotropium varied, as did the length of follow-up for patients. Given that death was a relatively rare event (<1%), estimates are imprecise. Even given these limitations, this study sheds light on the debate over the safety of tiotropium, specifically the mist-inhaler formulation. Caution should be used when prescribing the mist-inhaler formulation of tiotropium, and an understanding of the potential cardiovascular risks should be communicated to patients prior to initiating therapy.

Bottom line: This study shows that the mist-inhaler formulation of tiotropium is associated with an increased risk of cardiovascular mortality.

Citation: Singh S, Loke YK, Enright PL, Furnberg CD. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. Br Med J. 2011;342: d3215.

B-Type Natriuretic Peptide (BNP) Is an Independent Predictor of Cardiovascular Events in Patients Undergoing Vascular Surgery

Clinical question: Can preoperative natriuretic peptide levels be used to independently predict perioperative cardiovascular events in patients undergoing vascular surgery?

Background: Currently we use the type of surgery, exercise tolerance, and clinical risk factors to predict perioperative cardiovascular risk. Clinical risk factors, based on the Revised Cardiac Risk Index, or RCRI, include history of ischemic heart disease, heart failure, cerebrovascular events, diabetes mellitus, and renal insufficiency. Recent studies have shown that the pre-operative natriuretic peptides can independently predict perioperative cardiovascular events.

Study design: Individual patient meta-analysis.

Setting: Data sets obtained from six multinational studies.

Synopsis: This meta-analysis included datasets from five studies that used BNP (632 patients) and one study that used NT-proBNP (218 patients) to assess the postoperative cardiovascular events in patients undergoing vascular surgery. Patients with elevated BNP level are at a higher risk of cardiac death (OR 4.3, 95% CI: 1.7-11.3) and all-cause mortality (OR 3.1, 95% CI: 1.4-6.7) within 30 days of vascular surgery. When the RCRI-based groups were reclassified using natriuretic peptide level, the improvement in discrimination was statistically significant. Limitations of this study include: 1) Individual patient data was not obtained for all studies that met the search criteria; and 2) Different types of BNP assays were used in different studies included.

Bottom line: Preoperative BNP level is an independent predictor of cardiovascular events at 30 days after vascular surgery. The addition of preoperative BNP level improves the predictive performance of the RCRI score.

Citation: Rodseth RN, Lurati Buse GA, Bolliger D, et al. The predictive ability of pre-operative B-type natriuretic peptide in vascular patients for major adverse cardiac events: an individual patient data meta-analysis. J Am Coll Cardiol. 2011;58:522-529.

Beta-Blockers May be Beneficial in Patients with Chronic Obstructive Pulmonary Disease

Clinical question: Is it beneficial to use beta-blockers in patients with chronic obstructive pulmonary disease (COPD) if there is an indication?

Background: Patients with COPD may have concomitant cardiovascular disease, which may warrant use of beta-blockers. Many physicians are concerned about using beta-blockers in COPD patients due to the risk of bronchospasm. Evidence suggests that cardio-selective beta-blockers do not cause deterioration of pulmonary status in COPD patients. There is also growing evidence that beta-blockers may be beneficial in patients with COPD.

Study design: Retrospective cohort study.

Setting: Data obtained from a disease-specific (COPD) database in Scotland.

Synopsis: This study included 5,977 patients who were older than 50 and excluded patients with history of malignancy. Beta-blockers were associated with a 22% reduction in all-cause mortality. There was no significant difference between cardio-selective and nonselective beta-blockers. The benefits of beta-blockers in COPD patients were independent of history of cardiovascular disease. There was no significant decline in pulmonary function (FEV1) over time. Beta-blocker usage also reduced the number of hospital admissions for COPD exacerbation. These benefits were shown in patients using different type of inhalers.

Bottom line: In patients older than 50, beta-blockers may not only reduce COPD exacerbations and hospital admissions, but also reduce all-cause mortality without adversely affecting pulmonary function.

Citation: Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. Br Med J. 2011;342:d2549.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Atelectasis and fever
2. Heparin dosing frequency for VTE prophylaxis
3. Perioperative cardiac risk calculator
4. Diagnosing subarachnoid hemorrhage without an LP
5. Model to predict risk of bleeding on warfarin
6. Risk of death with tiotropium use in COPD
7. BNP to predict perioperative mortality
8. Beta-blockers and COPD

No Association Found between Atelectasis and Early Postopera-tive Fever

Clinical question: Is atelectasis really a major cause of early (up to 48 hours) postoperative fever (EPF)?

Background: Both fever and atelectasis are common findings in the postoperative period. EPF is believed to be noninfectious, and many textbooks consider atelectasis to be the most common cause. However, this association is controversial with no clear evidence.

Study design: Systematic review of prospective studies evaluating atelectasis and postoperative fever using PubMed and Scopus databases.

Setting: Postoperative patients (predominantly cardiac, maxillofacial, and abdominal surgeries). Lung surgery patients were excluded.

Synopsis: Eight prospective studies (four interventional and four observational) with 998 patients were included for review. All studies diagnosed atelectasis based on chest imaging but only three studies used the conventional definition of ≥38°C for fever. Seven studies individually reported no association between atelectasis and EPF.

Only five studies had eligible data for pooling and analysis. EPF was found to be a very weak indicator (diagnostic OR 1.4; 95% CI 0.92-2.12) of atelectasis. EPF also fared poorly for ruling out (sensitivity 13% to 47%) or ruling in (specificity 41% to 87%) the diagnosis of atelectasis with similarly poor positive and negative predictive values.

The results of this study, however, should be interpreted with caution. It was not a formal meta-analysis, due to the heterogeneity of the studies included with regard to the definition of fever, time points of imaging, and the variation of end points.

Bottom line: Since there is no clinical evidence to prove an association between atelectasis and fever, it is presumed that atelectasis may not be a cause of EPF.

Citation: Mavros MN, Velmahos GC, Falagas ME. Atelectasis as a cause of postoperative fever: where is the clinical evidence? Chest. 2011;140:418-424.

Unfractionated Heparin Can be Given Either BID or TID for Throm-boprophylaxis

Clinical question: Which is the best dosing frequency of unfractionated heparin (UFH) in preventing venous thromboembolism?

Background: Low-dose UFH is commonly used in hospitals for pharmacologic prophylaxis against venous thromboembolism. However, the risks and benefits of BID vs. TID dosing are not clear.

Study design: Mixed-treatment comparison (MTC) meta-analysis of RCTs.

Setting: RCTs on thromboprophylaxis regimens, selected from two previous systematic reviews and an updated literature search.

Synopsis: Included in the analysis were 27,667 patients from 16 RCTs comparing three prophylactic regimens (UFH BID, UFH TID, or low-molecular-weight heparin) with each other or with controls. Stroke and some myocardial infarction patients were excluded. The outcomes measured were DVT, pulmonary embolism (PE), major bleeding, and death. As compared with controls, all three regimens significantly reduced DVT (ranging from 58% to 72%), showed a nonsignificant trend toward reduction in PE (by 46% to 67%), and had no difference in risk of major bleeding or death.

UFH BID vs. TID were compared indirectly by using data from their trials against control patients or low-molecular-weight heparin. There was no significant difference between UFH TID and BID in reducing DVT (RR 1.56, CI 0.64-4.33), PE (RR 1.67, CI 0.49-208.9), mortality (RR 1.17, CI 0.72-1.95), or causing major bleeding (RR 0.89, CI 0.08-7.05). Additionally, both UFH dosing frequencies were similar to low-molecular-weight heparin in all four measured outcomes. This evidence is of moderate quality due to the lack of a direct comparison between UFH BID vs. TID.

Bottom line: Both BID and TID dosing of UFH are acceptable thromboprophylaxis regimens in hospitalized medical patients with no difference in effect on DVT, PE, major bleeding, or death.

Citation: Phung OJ, Kahn SR, Cook DJ, et al. Dosing frequency of unfractionated heparin thromboprophylaxis: a meta-analysis. Chest. 2011;140: 374-381.

New Cardiac-Risk Calculator Improves Prediction of Intra-/Postoperative Myocardial Infarction and Cardiac Arrest

Clinical question: Can a more accurate risk calculator than the Revised Cardiac Risk Index (RCRI) be developed and validated to predict postoperative cardiac events?

Background: The majority of perioperative deaths are secondary to cardiac-related events. The RCRI is the most commonly used preoperative risk stratification tool, but it has limitations and low discriminatory ability.

Study design: Multicenter prospective National Surgical Quality Improvement Program database study.

Setting: More than 250 academic and community U.S. hospitals.

Synopsis: Data were obtained from patients over a two-year period (2007 and 2008). From the 2007 data set (n=211,410), perioperative myocardial infarction or cardiac arrest (MICA) was seen in 1,371 patients (0.65%). After multivariate analysis on the 2007 data set, five risk predictors were obtained (increasing age, American anesthesiology class, dependent functional status, abnormal serum creatinine of >1.5 mg/dL, and type of surgery). This was validated utilizing the 2008 data set (n=257,385), where MICA was seen in 1,401 patients (0.54%).

The risk-predictive model showed excellent discrimination (distinguishing between events and nonevents) after application of C statistics to the dataset. The discriminatory ability was better when compared with the RCRI model. Limitations included nonavailability of information on preoperative stress test, arrhythmia, and aortic valve disease.

Bottom line: The new risk calculator model would help predict MICA more accurately, which in turn would help in preoperative optimization and patient counseling.

Citation: Gupta PK, Gupta H, Sundaram A, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circ. 2011;124:381-387.

Third-Generation CT Scans are Very Sensitive in Detecting Subarachnoid Hemorrhage

Clinical question: Are modern third-generation CT scans good enough to exclude subarachnoid hemorrhage (SAH) without a lumbar puncture (LP)?

Background: SAH is a neurosurgical emergency identified in about 1% of patients with headache in the emergency department. As the standard of care, all patients with suspected SAH have to undergo LP if a CT scan of the brain is normal. However, LP causes pain and delays discharge from the emergency department.

Study design: Prospective multicenter cohort study.

Setting: Eleven tertiary-care Canadian emergency departments.

Synopsis: From November 2000 to December 2009, data on all alert patients (n=3,132) who presented with acute headache and underwent emergent head CT were collected. Of these, 240 had SAH (7.7%). The sensitivity of CT overall for detecting SAH was 92.9% and the specificity was 100%. For the 953 patients scanned within six hours of headache onset, all 121 patients with SAH were identified by CT, yielding a sensitivity of 100% and specificity of 100%.

The study was limited largely by the lack of a consensus definition on the diagnosis of SAH and by some patient enrollment issues in the emergency department. Overall, these findings should give clinicians more confidence in forgoing an LP in patients with a negative head CT if done within six hours of the onset of their headache.

Bottom line: Modern third-generation CT scans are extremely sensitive for SAH if performed within six hours of the headache onset and interpreted by a qualified radiologist, thus possibly excluding the need for an LP.

Citation: Perry JJ, Stiell IG, Sivilotti ML, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. Br Med J. 2011;343:d4277.

Improved Model Stratifies Risk of Warfarin-Associated Bleeding in Patients with Atrial Fibrillation

Clinical question: Can a simple scoring model accurately assess the risk of warfarin-associated bleeding in a cohort of patients with atrial fibrillation?

Background: It is well known that anticoagulants, such as warfarin, dramatically reduce the risk of thromboembolic events in patients with atrial fibrillation. Despite this, clinicians often find themselves weighing the risks and benefits of anticoagulation in this cohort of patients, and improved models to assess those risks are needed.

Study design: Retrospective cohort study.

Setting: Kaiser Permanente of Northern California.

Synopsis: From a cohort of 13,559 adult patients with atrial fibrillation, the investigators used chart review to determine hemorrhagic events in this population and developed a model using Cox regression to assess hemorrhagic risk in certain patient populations. Final input variables for the model included anemia, severe renal disease, age ≥75, prior hemorrhage, and hypertension. When collapsed into three risk tiers (low, intermediate, and high), the scoring model nicely differentiated low (<1% annual) from high (5.8% annual) bleeding risk.

This study is limited by the lack of information on concomitant use of NSAIDs or aspirin in these patients and the lack of external validation of the model. Despite those limitations, it may serve as a valuable tool for clinicians. As the number of alternatives to warfarin rise and as those agents become more familiar, it will become increasingly important to accurately assess hemorrhage risk with various anticoagulants.

Bottom line: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk scoring system is a reliable and easy way for clinicians to estimate the degree of bleeding risk in patients anticoagulated with warfarin for atrial fibrillation.

Citation: Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study. J Am Coll Cardiol. 2011;58:395-401.

Tiotropium Mist Inhaler Associated with Increased Mortality

Clinical question: Does the mist-inhaler formulation of tiotropium increase mortality in patients with chronic obstructive pulmonary disease (COPD) when compared with placebo?

Background: Tiotropium is used in patients with COPD to reduce both symptoms of dyspnea and exacerbations of COPD. Tiotropium comes in two formulations: a powder (approved in the U.S.) and the mist inhaler (not approved in the U.S. but approved in 55 other countries). There are concerns based on recent studies that tiotropium may increase cardiovascular events and death.

Study design: Meta-analysis of five randomized controlled trials (RCTs) comparing tiotropium mist inhaler with a placebo.

Setting: Multinational studies.

Synopsis: This study of 6,522 patients with COPD showed a 52% increased risk of all-cause mortality with the use of the tiotropium mist inhaler when compared with placebo. It is important to note that there are data showing higher plasma concentrations with the approved mist-inhaler doses when compared with the powder formulation doses. Further, a possible dose effect was seen in this study (though not statistically significant), with higher tiotropium doses associated with a high-risk ratio for the mortality endpoint.

Limitations of this study include the fact that the dosage of the tiotropium varied, as did the length of follow-up for patients. Given that death was a relatively rare event (<1%), estimates are imprecise. Even given these limitations, this study sheds light on the debate over the safety of tiotropium, specifically the mist-inhaler formulation. Caution should be used when prescribing the mist-inhaler formulation of tiotropium, and an understanding of the potential cardiovascular risks should be communicated to patients prior to initiating therapy.

Bottom line: This study shows that the mist-inhaler formulation of tiotropium is associated with an increased risk of cardiovascular mortality.

Citation: Singh S, Loke YK, Enright PL, Furnberg CD. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. Br Med J. 2011;342: d3215.

B-Type Natriuretic Peptide (BNP) Is an Independent Predictor of Cardiovascular Events in Patients Undergoing Vascular Surgery

Clinical question: Can preoperative natriuretic peptide levels be used to independently predict perioperative cardiovascular events in patients undergoing vascular surgery?

Background: Currently we use the type of surgery, exercise tolerance, and clinical risk factors to predict perioperative cardiovascular risk. Clinical risk factors, based on the Revised Cardiac Risk Index, or RCRI, include history of ischemic heart disease, heart failure, cerebrovascular events, diabetes mellitus, and renal insufficiency. Recent studies have shown that the pre-operative natriuretic peptides can independently predict perioperative cardiovascular events.

Study design: Individual patient meta-analysis.

Setting: Data sets obtained from six multinational studies.

Synopsis: This meta-analysis included datasets from five studies that used BNP (632 patients) and one study that used NT-proBNP (218 patients) to assess the postoperative cardiovascular events in patients undergoing vascular surgery. Patients with elevated BNP level are at a higher risk of cardiac death (OR 4.3, 95% CI: 1.7-11.3) and all-cause mortality (OR 3.1, 95% CI: 1.4-6.7) within 30 days of vascular surgery. When the RCRI-based groups were reclassified using natriuretic peptide level, the improvement in discrimination was statistically significant. Limitations of this study include: 1) Individual patient data was not obtained for all studies that met the search criteria; and 2) Different types of BNP assays were used in different studies included.

Bottom line: Preoperative BNP level is an independent predictor of cardiovascular events at 30 days after vascular surgery. The addition of preoperative BNP level improves the predictive performance of the RCRI score.

Citation: Rodseth RN, Lurati Buse GA, Bolliger D, et al. The predictive ability of pre-operative B-type natriuretic peptide in vascular patients for major adverse cardiac events: an individual patient data meta-analysis. J Am Coll Cardiol. 2011;58:522-529.

Beta-Blockers May be Beneficial in Patients with Chronic Obstructive Pulmonary Disease

Clinical question: Is it beneficial to use beta-blockers in patients with chronic obstructive pulmonary disease (COPD) if there is an indication?

Background: Patients with COPD may have concomitant cardiovascular disease, which may warrant use of beta-blockers. Many physicians are concerned about using beta-blockers in COPD patients due to the risk of bronchospasm. Evidence suggests that cardio-selective beta-blockers do not cause deterioration of pulmonary status in COPD patients. There is also growing evidence that beta-blockers may be beneficial in patients with COPD.

Study design: Retrospective cohort study.

Setting: Data obtained from a disease-specific (COPD) database in Scotland.

Synopsis: This study included 5,977 patients who were older than 50 and excluded patients with history of malignancy. Beta-blockers were associated with a 22% reduction in all-cause mortality. There was no significant difference between cardio-selective and nonselective beta-blockers. The benefits of beta-blockers in COPD patients were independent of history of cardiovascular disease. There was no significant decline in pulmonary function (FEV1) over time. Beta-blocker usage also reduced the number of hospital admissions for COPD exacerbation. These benefits were shown in patients using different type of inhalers.

Bottom line: In patients older than 50, beta-blockers may not only reduce COPD exacerbations and hospital admissions, but also reduce all-cause mortality without adversely affecting pulmonary function.

Citation: Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. Br Med J. 2011;342:d2549.

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.