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Articles 
Davinder P.S. Dosanjh, Timothy S.C. Hinks, John A. Innes, Jonathan J. Deeks, Geoffrey Pasvol, Sarah Hackforth, Hansa Varia, Kerry A. Millington, Rubamalar Gunatheesan, Valerie Guyot-Revol, and Ajit Lalvani Dosanjh and colleagues investigated the ability of 2 T-cell–based blood tests (ELISpot and ELISpotPLUS) to rule out active tuberculosis. In 389 adults with moderate to high suspicion of active tuberculosis, the sensitivity of ELISpotPLUS was higher than that of 15-mm threshold tuberculin skin testing (TST) (89% vs. 79%) and similar to that of 10-mm threshold TST (83%) in unvaccinated patients for identifying culture-confirmed and highly probable tuberculosis. Patients with negative results on both ELISpotPLUS and TST had a very low likelihood ratio for tuberculosis. The ELISpotPLUS assay, particularly when used in combination with TST, can help to rule out active tuberculosis.
Jeffrey A. Tice, Steven R. Cummings, Rebecca Smith-Bindman, Laura Ichikawa, William E. Barlow, and Karla Kerlikowske Existing breast cancer prediction tools do not account for breast density, a strong risk factor for breast cancer. Tice and associates developed a breast cancer risk prediction model that incorporates a measure of breast density that radiologists routinely report with mammography. Its predictions were accurate, but it had only modest ability to distinguish women who did not develop cancer from those who did. Before it is used in patient care, the model requires validation in additional populations to more fully characterize its accuracy.
Mariana Lazo, Elizabeth Selvin, and Jeanne M. Clark The authors analyzed the results of performing repeated liver function tests about 17 days apart. The population was 1864 men and women in the Third National Health and Nutrition Examination Survey. More than 95% of the initially normal results remained normal, whereas 12% to 38% of abnormal results had reverted to normal at the second examination. Because of this high intraindividual variability, the authors suggest that practice guidelines should recommend repeating liver tests in asymptomatic persons with abnormal results.
Improving Patient Care
Bruce E. Landon and Sharon-Lise T. Normand A majority of U.S. internists work in practices with 4 or fewer physicians. This article reviews the practice landscape in the United States; describes performance measurement challenges in small practices, including financial and staffing implications; discusses statistical issues that affect assessment of practice quality; and describes potential solutions.
Reviews
Luigi Marchionni, Renee F. Wilson, Antonio C. Wolff, Spyridon Marinopoulos, Giovanni Parmigiani, Eric B. Bass, and Steven N. Goodman Three gene expression–based breast cancer prognostication tests have been licensed for use: Oncotype DX, MammaPrint, and H/I. The authors summarize the evidence on the validity and utility of these tests. Overall, the body of evidence showed that this new generation of tests may improve prognostication and prediction of response to specific therapies. The tests offer clinically important improvement in risk stratification compared with standard outcome predictors.
Clinical Guidelines
Amir Qaseem, Vincenza Snow, J. Thomas Cross, Jr., Mary Ann Forciea, Robert Hopkins, Jr., Paul Shekelle, Alan Adelman, David Mehr, Kenneth Schellhase, Doug Campos-Outcalt, Pasqualina Santaguida, Douglas K. Owens the Joint American College of Physicians/American Academy of Family Physicians Panel on Dementia The American College of Physicians and American Academy of Family Physicians offer recommendations on current pharmacologic treatment of dementia. Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or memantine on individualized assessment (weak recommendation, moderate-quality evidence). In addition, they should base the choice of agent on tolerability, adverse effect profile, ease of use, and cost. The evidence is insufficient to compare the effectiveness of different agents for the treatment of dementia (weak recommendation, low-quality evidence).
Parminder Raina, Pasqualina Santaguida, Afisi Ismaila, Christopher Patterson, David Cowan, Mitchell Levine, Lynda Booker, and Mark Oremus Raina and associates reviewed the evidence for the effectiveness of cholinesterase inhibitors and memantine in achieving clinically relevant improvements in patients with dementia. Consistent differences between cholinesterase inhibitors and memantine were found for cognition and global assessment, but effect sizes were small. Behavioral and quality-of-life outcomes showed less consistent effects. Drug treatment of dementia results in cognitive improvement that is statistically significant but not consistently clinically important.
Editorials
Dick Menzies In this issue, Dosanjh and colleagues present results from using a combination of tuberculin skin testing (TST) and an interferon-
George L. Bakris and Michael Berkwits The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicon-MR Controlled Evaluation) trial tested whether perindopril, 2 mg/d, and indapamide, 0.625 mg/d, plus standard antihypertensive treatment reduced both the microvascular and macrovascular complications of diabetes. Compared with placebo, participants taking the drug combination had a statistically significant mean reduction in systolic and diastolic blood pressure and a borderline statistically significant reduction in major macrovascular and microvascular events. Because the mean blood pressure of participants was lower than that of participants in previous trials, the ADVANCE trial provides new evidence that starting antihypertensives at a prehypertensive stage in patients with type 2 diabetes is beneficial.
Letters Biological Significance of Anti–Cyclic Citrullinated Peptide Antibody in Rheumatoid Arthritis
Ronenn Roubenoff, Evan Beckman, Michael Weinblatt, Nancy Shadick, and Peter K. Gregersen β-Blockers and Progression of Coronary Atherosclerosis
Can't We Improve on Advance Directives?
Anaphylactic Shock with Multiorgan Failure in a Cyclist after Intravenous Administration of Actovegin
Correction: In the Clinic: Dyslipidemia
Correction: In the Clinic: Migraine
Correction: Risk for Fatal Pulmonary Embolism after Discontinuing Anticoagulation
Paul Rousseau
This issue provides a clinical overview of chronic obstructive pulmonary disease, focusing on prevention, diagnosis, treatment, practice improvement, and patient information. Readers can complete the accompanying CME quiz for 1.5 credits. | |||||||||||||||||||||||||||||||||||||||||
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release assay (ELISpotPLUS) to diagnose active tuberculosis. Sensitivity was 99% in patients with positive TST or ELISpotPLUS results. However, several studies and a systematic review and meta-analysis are required before we can be confident that the sensitivity is truly this high. In the meantime, physicians who strongly suspect tuberculosis despite negative results on both TST and ELISpotPLUS should follow the patient closely before ruling out active tuberculosis. 