Adefovir Dipivoxil in HBeAg-Negative Chronic Hepatitis B
In the second phase of a randomized, placebo-controlled trial of adefovir dipivoxil for the treatment of hepatitis B e antigen (HBeAg)negative chronic hepatitis B, patients who had been treated with adefovir during the initial 48 weeks of the trial were randomly assigned to be switched to placebo or to continue to receive adefovir. Patients who were switched to placebo lost the benefits that had been gained during the initial 48 weeks of treatment, and patients randomly assigned to continue adefovir therapy maintained a response. Resistance mutations developed in 6 percent of the patients treated with adefovir dipivoxil for 144 weeks.
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Peginterferon Alfa-2a in HBeAg-Positive Chronic Hepatitis B
After 48 weeks of treatment and 24 weeks of follow-up, patients treated with peginterferon either alone or in combination with lamivudine were more likely to have HBeAg seroconversion than patients treated with lamivudine alone (32 percent and 27 percent vs. 19 percent) and more likely to have HBV DNA levels below 100,000 copies per milliliter (32 percent and 34 percent vs. 22 percent). A 48-week course of peginterferon alfa-2a is more effective than 48 weeks of lamivudine for HBeAg-positive chronic hepatitis B.
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Capecitabine as Adjuvant Treatment for Stage III Colon Cancer
The standard combination of intravenous fluorouracil plus leucovorin for adjuvant treatment of colon cancer was compared with the oral fluoropyrimidine capecitabine in almost 2000 patients with resected colon cancer. With disease-free survival as the primary end point, capecitabine was at least as effective as fluorouracil plus leucovorin. The oral drug had fewer side effects than the intravenous combination.
The finding that a single oral drug is at least as effective as intravenous chemotherapy promises, if confirmed, to be an important step forward in the management of resected colon cancer.
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Daclizumab to Prevent Rejection after Heart Transplantation
Daclizumab is a humanized monoclonal antibody directed against the interleukin-2 receptor and thereby inhibits T-cell proliferation. In this clinical trial, daclizumab reduced the risk of cellular rejection in heart-transplant recipients when it was added to a regimen of cyclosporine, mycophenolate mofetil, and corticosteroids. However, when daclizumab was given concurrently with cytolytic therapy, there was a worrisome increase in the rate of death from infection.
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Lung Cancer Screening
A 60-year-old woman who quit smoking 20 years earlier comes for a routine visit. She previously smoked one pack of cigarettes a day for 10 years. Her medical history is otherwise unremarkable. Her husband smoked one pack of cigarettes per day for at least 30 years but stopped smoking a decade ago. She asks whether she and her husband should undergo computed tomographic scanning to screen for lung cancer. What do you advise?
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Drug Therapy: -Hydroxybutyric Acid
The short-chain fatty acid -hydroxybutyric acid (GHB), which is synthesized as an analogue of -aminobutyric acid (GABA) that would cross the bloodbrain barrier, has found limited clinical use as an anesthetic agent and as treatment for narcolepsy and alcoholism. However, during the past decade, GHB has emerged as a major recreational drug in the United States. This review article discusses the mechanisms of action and presents an approach to the treatment of overdose, abuse, and addiction.
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A Man with Locally Advanced Pancreatic Cancer
A 58-year-old man was being evaluated for an abdominal aortic aneurysm when a pancreatic mass was incidentally found; in retrospect, he had experienced vague abdominal discomfort and weight loss for several months. Further evaluation disclosed a pancreatic adenocarcinoma that encased the superior mesenteric and portal veins. Treatment options are discussed.
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