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April 26, 2007  Vol. 356 No. 17

Audio Summary of this Issue

Perspective
1697-1700

Since 1992, the United States has relied heavily on the pharmaceutical industry to pay the salaries of FDA scientists who review new drug applications. Dr. Jerry Avorn writes that most federal regulatory agencies do not derive such a large proportion of ...

1700-1702

Major legislation on drug safety is almost certain to be enacted before fall, as Congress reauthorizes the Prescription Drug User Fee Act (PDUFA). Dr. Mark McClellan writes that this represents an opportunity to implement a more systematic approach to ...

1703-1704

The FDA is proposing to devote only $29.3 million to modernizing and transforming the drug-safety system. Sean Hennessy and Dr. Brian Strom write that Congress should take advantage of this opportunity to provide a robust level of funding for postapproval ...

1705-1707

Because randomized studies are rarely well powered for evaluating adverse effects of treatment, well-designed observational studies are important. Michael Hughes and Paige Williams discuss the complex questions concerning both the potential confounding of ...

1707-1709

Mitochondrial dynamics are now a focus of cell biologists, but are these processes physiologically and clinically important? Dr. David Chan suggests that we may find additional diseases caused by mutations in genes that control mitochondrial fusion and ...

Original Articles
1711-1722

The risks and benefits of standard antidepressants for patients with bipolar disorder are not well understood. In this randomized, placebo-controlled trial of patients with bipolar disorder, all of whom received a mood stabilizer, adjunctive treatment with an antidepressant did not reduce the symptoms of bipolar depression or increase the risk of mania.

1723-1735

In patients infected with HIV, the duration of combination antiretroviral therapy has been shown to be associated with the risk of myocardial infarction (MI). In an analysis of data from 23,437 patients, a significant association with risk of MI was found for protease-inhibitor therapy but not for therapy with nonnucleoside reverse-transcriptase inhibitors. This association may be partly explained by the effects of protease inhibitors on serum lipid levels.

1736-1741

Some types of neuropathy are caused by mutant dynamin proteins, which prevent the fusion of mitochondria. In this article, an infant with severe and lethal neuropathy was found to have elongated, tubular mitochondria and peroxisomes and to carry a mutation in the gene encoding dynamin-like protein 1. The mutant protein seemed to prevent mitochondrial and peroxisomal fission.

Special Article
1742-1750
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In this national survey of 3167 physicians, 83% reported receiving food or beverages paid for by a company that makes drugs or other medical products, 78% drug samples, 35% reimbursement for professional meetings, and 28% payments for consulting, speaking, or enrolling patients in clinical trials. Family practitioners met most frequently with industry representatives, and cardiologists were most likely to receive payments.

Clinical Therapeutics
1751-1758

A 48-year-old man reports that he snores loudly and falls asleep when sedentary. A diagnosis of obstructive sleep apnea is made, and treatment with continuous positive airway pressure (CPAP) is recommended. CPAP has been shown to improve cognitive function and sleep quality, although beneficial effects on survival have not been clearly documented. The patient's tolerance of CPAP is often a limiting factor.

Videos in Clinical Medicine
e15

    Emergency orotracheal intubation is indicated in any situation that requires definitive control of the airway. This video demonstrates how to perform orotracheal intubation. Specific indications are discussed, along with contraindications, troubleshooting, and complications.

    Images in Clinical Medicine
    1759
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    A 50-year-old man presented for a routine physical examination for the first time in 10 years. He reported having had no recent health problems. He had a 60 pack-year smoking history and did not drink alcohol. During the examination, a painless, firm mass ...

    e16
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    This 20-year-old man presented with fever and abdominal pain. He began peritoneal dialysis at the age of 4 years because of nephropathy.

    Case Records of the Massachusetts General Hospital
    1760-1769

    A 46-year-old woman was evaluated at the Center for Cancer Risk Analysis because of her recent diagnoses of endometrial, ovarian, and colon cancers. A routine Papanicolaou smear had disclosed an atypical glandular cell; endometrial curettage disclosed endometrioid carcinoma; and at hysterectomy, small bilateral ovarian tumors and a colon cancer were found. There was a maternal history of endometrial, breast, and colon cancers and colonic polyps.

    Editorials
    1771-1773

    Bipolar disorder consists of depressive episodes of low mood, difficulty in concentration and work, poor sleep, and poor appetite, as well as distinct manic episodes of expansive mood, pressured speech, overactivity, sexual excesses, aggressiveness, and ...

    1773-1775

    Treatment with potent antiretroviral therapy has transformed human immunodeficiency virus (HIV) infection from a rapidly fatal disease into a chronic illness that some patients can live with for more than two decades. However, shortly after antiretroviral ...

    Clinical Implications of Basic Research
    1776-1778

    Some adjuvants contain ligands that bind to a specific class of dendritic-cell receptors called toll-like receptors. Binding of ligand to toll-like receptors was thought to initiate the immune response and underlie the adjuvant effect. A recent study questions this assumption.

    Correspondence
    1779-1780

    To the Editor: Cuchel and colleagues (Jan. 11 issue)1 report that inhibition of the microsomal triglyceride transfer protein reduces plasma low-density lipoprotein (LDL) cholesterol in homozygous familial hypercholesterolemia — a finding that establishes ...

    1780

    To the Editor: Druker et al. (Dec. 7 issue)1 update the data for patients who received imatinib as first-line therapy for chronic myeloid leukemia (CML). However, they do not present most of the data according to the intention-to-treat principle. The ...

    1781-1782

    To the Editor: In the report by Wang et al. (July 20 issue)1 about mutant neurogenin-3 in patients with congenital malabsorptive diarrhea, patients with the R93L and R107S mutations of the neurogenin-3 gene (NEUROG3) had congenital diarrhea and sparse ...

    1782-1784

    To the Editor: Lindenauer et al. (Feb. 1 issue)1 report that hospital participation in the Centers for Medicare and Medicaid Services (CMS) Premier Hospital Quality Incentive Demonstration (HQID), or pay for performance, was associated with modest but ...

    1785-1787

    To the Editor: In the article by Binswanger and colleagues (Jan. 11 issue),1 the mortality among former prisoners in Washington State — 777 deaths per 100,000 person-years — is striking. The investigators followed released inmates for a mean period of ...

    1787-1789
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    To the Editor: In the Clinical Practice article on concussion by Ropper and Gorson (Jan. 11 issue),1 the discussion of sport-related concussion is outdated — especially, the definition of concussion. The review is also inaccurate regarding the risk of ...

    1789-1790

    To the Editor: We have enjoyed watching the Journal's new procedural videos and applaud their emphasis on proper procedural techniques. This new approach to procedural training complements a trend at a few institutions that are taking patient safety to ...

    Book Reviews
    1791-1792

    Psychoanalysis was for its founder, Sigmund Freud, three things — a form of psychotherapy, a theory of the mind, and a method of psychological inquiry. Today we might add a fourth — a profession with thousands of members around the world. Now in its ...

    1792

    To the busy physician, increasingly squeezed by the demands of managed care and distanced from patients by tests and technologies, empathy might seem like a luxury or an irrelevance. The concept itself can seem vague and impractical. Empathy is sometimes ...

    1793-1794

    The first thing readers should know about this engaging and important book is that it is apparently dangerous to one's reputation to read it in the presence of academic physicians. I noticed this as I sat and read it in various locations at my own medical ...

    Correction
    1794
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    Concussion Clinical Practice, N Engl J Med 2007:356;166-172.. The second sentence of the article (page 166) should have read “This event is so common, affecting about 128 people per 100,000 population in the United States yearly,1 that almost all ...

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