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ACP HospitalistWeekly

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In the News for the Week of 1-25-12

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Highlights

Hyperglycemia guideline suggests glucose testing for all inpatients

A new clinical practice guideline from the Endocrine Society offers recommendations on identifying and managing hyperglycemia in non-critical-care inpatients. More...

Optimal potassium level after MI differs from guidelines, study finds

Post-myocardial infarction inpatients with blood potassium levels between 3.5 and 4.5 mEq/L had a lower mortality risk than those with levels higher or lower than this range, a new study found. More...

High-value care

College workgroup compiles list of unnecessary tests

A workgroup of internists convened by ACP has developed a list of 37 clinical situations in which medical tests are commonly used but do not provide high value. More...

Depression

Antidepressants work for patients with comorbidities

Patients with comorbidities can be safely and effectively treated for major depressive disorder (MDD) with antidepressants, even combination therapy, with no more adverse effects than their healthier counterparts, researchers concluded. More...

Perioperative care

Cangrelor shows promise as bridging antiplatelet therapy in CABG patients

Among patients who discontinued thienopyridine therapy before cardiac surgery, those who used the investigational drug cangrelor had better maintenance of platelet inhibition than those who used placebo, a study found. More...

FDA update

Brentuximab gets boxed warning

A boxed warning has been added to lymphoma drug brentuximab vedotin (Adcetris) regarding its rare association with progressive multifocal leukoencephalopathy (PML). More...

Possibility of mixed drugs from Endo Pharmaceuticals

The FDA recently warned physicians and the public about the possibility of packaging mixups of some prescription opiate medications and over-the-counter non-opiate products manufactured and packaged for Endo Pharmaceuticals by Novartis Consumer Health. More...

From the College

ACP Job Placement Center calls for job seekers' profiles

Physicians looking for a new job may submit a Job Seeker's Profile to the ACP Job Placement Center, a service available at Internal Medicine 2012, to be held April 19-21 in New Orleans. More...

Internal Medicine 2013 proposals sought

The Clinical Skills Committee (CSC) is now accepting proposals for Internal Medicine 2013, to be held April 11-13, 2013. More...

Cartoon caption contest

Put words in our mouth

ACP HospitalistWeekly wants readers to create captions for our new cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service. More...

Physician editor: A. Scott Keller, MD, FACP

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Highlights

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Hyperglycemia guideline suggests glucose testing for all inpatients

A new clinical practice guideline from the Endocrine Society offers recommendations on identifying and managing hyperglycemia in non-critical-care inpatients.

The evidence-based guideline was developed by an expert task force and reviewed by the Endocrine Society, American Diabetes Association, American Heart Association, American Association of Diabetes Educators, European Society of Endocrinology and the Society of Hospital Medicine. The recommendations are intended to offer "practical, achievable, and safe glycemic targets and describe protocols, procedures, and system improvements required to facilitate the achievement of glycemic goals," according to the guideline.

Eight different subject areas are covered under the guideline, including diagnosis and recognition of hyperglycemia and diabetes, monitoring glycemia, glycemic targets, management of hyperglycemia, recognition and management of hypoglycemia, implementation of glycemic control programs, patient and professional education, and special situations (including surgery and glucocorticoids).

The guidelines' conclusions include:

• A suggestion that all patients have laboratory blood glucose testing on admission (very low-quality evidence),
• A recommendation that non-diabetic patients with a blood glucose over 140 mg/dL be monitored with bedside point of care testing for at least 24 to 48 hours (very low-quality evidence),
• A recommendation for the majority of patients that blood glucose targets be under 140 mg/dLl premeal and under 180 mg/dL at random testing (low-quality evidence),
• A suggestion to discontinue oral hypoglycemic agents and initiate insulin therapy for the majority of patients with type 2 diabetes at the time of hospital admission for an acute illness (very low-quality evidence),
• A recommendation of insulin therapy as the preferred method for glycemic control in hospitalized patients (low-quality evidence),
• A suggestion to avoid prolonged use of sliding scale insulin in patients with diabetes (very low-quality evidence),
• A recommendation to give scheduled subcutaneous insulin therapy consisting of basal or intermediate-acting insulin once or twice a day in combination with rapid- or short-acting insulin administered before meals in patients who are eating (moderate-quality evidence),
• A recommendation to discontinue oral and non-insulin injectable antidiabetics before surgery (very low-quality evidence), and
• A recommendation for implementation of a standardized nurse-initiated hypoglycemia treatment protocol, initiated when blood glucose is less than 70 mg/dl (low-quality evidence).

The clinical practice guideline was published in the February 2012 Journal of Clinical Endocrinology and Metabolism and released early online.

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Optimal potassium level after MI differs from guidelines, study finds

Post-myocardial infarction inpatients with blood potassium levels between 3.5 and 4.5 mEq/L had a lower mortality risk than those with levels higher or lower than this range, a new study found.

Current guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L in acute myocardial infarction (AMI) patients, but most studies on which the guidelines are based occurred before the routine use of beta-blockers, reperfusion therapy and early invasive management for eligible patients, the study authors noted. Those previous studies also focused on ventricular arrhythmias, not mortality, they said.

For their retrospective cohort study, the researchers examined data from 38,689 patients with AMI confirmed by biomarkers, who were admitted to 67 U.S. hospitals from 2000 through 2008. All patients had serum potassium measured in the hospital and were categorized by mean level after admission as <3.0, 3.0 to <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, 5.0 to <5.5 or ≥5.5 mEq/L.

Researchers found a U-shaped relationship between mean post-admission potassium level and in-hospital mortality. Nearly 7% of study patients (n=2,679, or 6.9%) died during hospitalization. Compared with the reference group (3.5 to <4.0 mEq/L; mortality rate, 4.8%), the group with levels of 4.0 to <4.5 mEq/L had similar mortality (5.0%). Patients with levels of 4.5 to <5.0 mEq/L had double the mortality rate (10%), and mortality was even higher for those at 5.0 mEq/L or higher.

Mortality rates were also higher for patients with potassium levels <3.5 mEq/L. However, rates of ventricular arrhythmias or cardiac arrest were higher (compared to the reference group) only for those with the lowest and highest average potassium levels (i.e, <3.0 mEq/L and ≥5.0 mEq/L). The study was published in the Jan. 11 Journal of the American Medical Association.

The findings "challenge current clinical practice guidelines" and suggest the optimal range of potassium levels in AMI patients is between 3.5 and 4.5 mEq/L, while levels greater than 4.5 mEq/L "should probably be avoided," the authors wrote. Editorialists largely agreed, saying potassium repletion for levels lower than 3.5 mEq/L "remains reasonable," while repletion for levels between 3.5 mEq/L and 4.0 mEq/L doesn't seem justified—and neither does targeting levels above 4.5 mEq/L.

High-value care

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College workgroup compiles list of unnecessary tests

A workgroup of internists convened by ACP has developed a list of 37 clinical situations in which medical tests are commonly used but do not provide high value.

The list was developed by a consensus-based process and published in the Jan. 17 Annals of Internal Medicine, with a goal of promoting thoughtful discussions about which tests and interventions promote high-value, cost-conscious care. The list includes a variety of inpatient and outpatient situations in which the experts felt use of a test may provide no benefit or be harmful, including several cardiac tests, cancer screens and monitoring practices.

Situations on the list particularly likely to be encountered by hospitalists include:

• Measuring brain natriuretic peptide in the initial evaluation of patients with typical findings of heart failure,
• Performing predischarge chest radiography for hospitalized patients with community-acquired pneumonia who are making a satisfactory clinical recovery,
• Obtaining CT scans in a patient with pneumonia that is confirmed by chest radiography in the absence of complicating clinical or radiographic features,
• Performing imaging studies, rather than a high-sensitivity D-dimer measurement, as the initial diagnostic test in patients with low pretest probability of venous thromboembolism,
• Measuring D-dimer rather than performing appropriate diagnostic imaging (extremity ultrasonography, CT angiography, or ventilation–perfusion scintigraphy) in patients with intermediate or high probability of venous thromboembolism,
• Performing preoperative chest radiography in the absence of a clinical suspicion for intrathoracic pathology,
• Ordering routine preoperative laboratory tests, including complete blood count, liver chemistry tests, and metabolic profiles, in otherwise healthy patients undergoing elective surgery, and
• Performing preoperative coagulation studies in patients without risk factors or predisposing conditions for bleeding and with a negative history of abnormal bleeding.

The workgroup also suggested some general principles for providing high-value care in testing. First, diagnostic tests usually should not be performed if results will not change management. Second, in situations where the pre-test probability of disease is low, the likelihood of a false-positive could be higher than the likelihood of a true-positive, potentially leading to expensive and harmful further testing. Finally, when considering the cost of a test, downstream costs, such as follow-up testing, should be considered, the group said.

An editorial accompanying the article noted that some physicians will likely take issue with some of the items on the list and invited all readers of the article to take a brief web survey to indicate their agreement or disagreement with the list. The editorial also suggested a number of questions that physicians should ask themselves in order to determine whether a test will provide high value, including whether the test results are available from another source, what effects giving or not giving the test are likely to have, and whether the test is being ordered primarily to reassure the patient.

Depression

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Antidepressants work for patients with comorbidities

Patients with comorbidities can be safely and effectively treated for major depressive disorder (MDD) with antidepressants, even combination therapy, with no more adverse effects than their healthier counterparts, researchers concluded.

The Combining Medications to Enhance Depression Outcomes (CO-MED) trial consisted of 12 weeks of acute care and 16 weeks of follow-up treatment. It was a multisite, single-blind, randomized trial that compared the efficacy of traditional selective serotonin reuptake inhibitor (SSRI) monotherapy (escitalopram plus placebo) versus that of two antidepressant medication combinations (escitalopram plus bupropion-SR and venlafaxine-XR plus mirtazapine) in patients with chronic and/or recurrent, nonpsychotic MDD. Clinicians were not blinded to maximize safety and to allow them to make informed flexible dosing decisions.

Patients underwent the Self-Administered Comorbidity Questionnaire, a self-report that assesses the presence of medical problems, their severity, and whether the condition limits functioning. Conditions on the questionnaire included heart disease, high blood pressure, lung disease, diabetes, gastrointestinal tract disorders, kidney disease, liver disease, anemia or other blood disease, cancer, arthritis, thyroid disease, and chronic back pain. Also, respondents could add three more conditions.

At 12 and 28 weeks, researchers compared unadjusted and adjusted outcomes (symptom severity, tolerability and functioning) among patients with none, one, two, and three or more general medical conditions. Results appeared in the January/February Annals of Family Medicine.

Of the 665 evaluable patients, 328 (49.5%) reported having no general medical conditions, 158 (23.8%) reported having one condition, 98 (14.8%) reported having two conditions and 79 (11.9%) reported having at least three conditions. (Two participants did not complete the questionnaire.)

There were no differences in outcomes associated with antidepressant monotherapy and either of the antidepressant combination therapies, regardless of the number of general medical conditions a patient had. Specifically, within each group having a given number of conditions, the three treatments did not differ significantly by efficacy or tolerability at weeks 12 and 28.

The authors concluded that the almost complete lack of difference among patients with differing numbers of conditions shows that all patients can receive equally safe and effective treatment for MDD with antidepressants without risk of additional adverse effects or intolerability. Combination antidepressant therapy had no additional benefit over SSRI monotherapy for patients with general medical conditions and comorbid, chronic or recurrent MDD.

"Not surprisingly, participants with general medical conditions and comorbid MDD were more likely to be treated for depression by their primary care physician than a psychiatric care professional," the authors wrote. "This greater likelihood of treatment in primary care could occur for a variety of reasons, the most obvious being that patients with general medical conditions and comorbid MDD may prefer to be treated by a single physician rather than use a separate mental health professional for their depression."

Perioperative care

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Cangrelor shows promise as bridging antiplatelet therapy in CABG patients

Among patients who discontinued thienopyridine therapy before cardiac surgery, those who used the investigational drug cangrelor had better maintenance of platelet inhibition than those who used placebo, a study found.

The researchers conducted a prospective, randomized, double-blind, placebo-controlled, multicenter trial with 210 patients who were randomized to cangrelor or placebo. All patients had an acute coronary syndrome or were treated with a coronary stent, and were receiving a thienopyridine prior to coronary artery bypass grafting surgery (CABG). Thienopyridines were stopped five to seven days before surgery, and patients were given placebo or 0.75 μg/kg of cangrelor per minute for at least 48 hours, which was stopped one to six hours before surgery. Infusion time for cangrelor was 2.8 days on average (median) and 3.4 days (median) for placebo. The main efficacy end point was platelet reactivity of less than 240 P2Y₁₂ Reaction Units (PRUs), assessed daily, and the main safety end point was excessive CABG-surgery-related bleeding.

The percentage of patients with platelet reactivity less than 240 PRUs throughout the infusion of the study drug was significantly higher than in the placebo group (98.8% vs. 19%; P<0.001). Excessive surgery-related bleeding was similar in both groups (11.8% in the cangrelor group vs. 10.4% in the placebo group; P=0.763). There were no significant differences in major bleeding before CABG surgery, although there were more episodes of minor bleeding with cangrelor. Results were published in the Jan. 19 Journal of the American Medical Association.

Cangrelor infusion "consistently achieved and maintained platelet inhibition at levels known to be associated with a low risk of thrombotic events compared with placebo," while not increasing major bleeding before surgery, the authors noted. It's a feasible management strategy to inhibit platelets in cardiac patients who are awaiting surgery and have discontinued use of thienopyridine, they concluded. The study was sponsored by The Medicines Company, and the authors disclosed ties to numerous industry sources.

FDA update

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Brentuximab gets boxed warning

A boxed warning has been added to lymphoma drug brentuximab vedotin (Adcetris) regarding its rare association with progressive multifocal leukoencephalopathy (PML).

At the time of the drug's approval in August 2011, one case of PML was described in the Warnings and Precautions section of the label. Since then, two additional cases have been reported. Due to the serious nature of PML, the boxed warning was added, according to an FDA statement. Clinicians should hold the drug if PML is suspected and discontinue it if a diagnosis of PML is confirmed.

In addition, a new contraindication was added against use of the drug in combination with bleomycin due to increased risk of pulmonary toxicity.

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Possibility of mixed drugs from Endo Pharmaceuticals

The FDA recently warned physicians and the public about the possibility of packaging mixups of some prescription opiate medications and over-the-counter non-opiate products manufactured and packaged for Endo Pharmaceuticals by Novartis Consumer Health. A stray pill of one medication may have ended up in the bottle of another product.

According to an FDA advisory, patients and health care professionals should examine opiate medicines made by Endo and ensure that all tablets are the same. The agency also expects shortages for these products and is working with the manufacturer to minimize the impact. A recall was issued for potentially affected over-the-counter products, including Excedrin, NoDoz, Bufferin and Gas-X.

From the College

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ACP Job Placement Center calls for job seekers' profiles

Physicians looking for a new job may submit a Job Seeker's Profile to the ACP Job Placement Center, a service available at Internal Medicine 2012, to be held April 19-21 in New Orleans. The Center, located in the New Orleans Ernest N. Morial Convention Center, Booth #430, provides physicians with tools to assist in job searches as well as the opportunity to meet with potential employers.

Profiles will be included in one of two booklets based on your criteria and distributed only to Job Placement Center sponsors and exhibitors who have submitted a job posting. After reviewing a profile, a recruiter may contact the physician to schedule a private on-site interview at the Center. Profiles can be submitted online.

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Internal Medicine 2013 proposals sought

The Clinical Skills Committee (CSC) is now accepting proposals for Internal Medicine 2013, to be held April 11-13, 2013. The CSC welcomes all proposals but places a priority on interactive workshops that focus on the acquisition or improvement of physical examination skills, communication skills and procedural skills.

The CSC is most interested in workshops that have a high likelihood of changing physician behavior using proven teaching techniques or new and innovative teaching strategies that have yet to be tested. To submit a proposal to the committee, please contact Ted Warren or go to the ACP Future Meetings page for the Internal Medicine 2013 application.

The deadline for proposals is May 21, 2012.

Cartoon caption contest

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Put words in our mouth

ACP HospitalistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.

E‑mail all entries to acphospitalist@acponline.org. ACP staff will choose finalists and post them online for an online vote by readers. The winner will appear in an upcoming edition.

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