This Week in JAMA FREE

Lactoferrin—the major whey protein in mammalian milk—is involved in immune defense. In a placebo-controlled randomized trial, Manzoni and colleagues Article investigated whether oral administration of bovine lactoferrin, alone or in combination with the probiotic Lactobacillus rhamnosus GG, reduces the incidence of late-onset sepsis among very low-birth-weight neonates. The authors found that compared with infants who received placebo, the incidence of late-onset sepsis was significantly lower among infants who received bovine lactoferrin supplementation from birth until day 30 of life. In an editorial, Kaufman Article discusses the mechanisms of action of lactoferrin and prevention of nosocomial infections in preterm infants.

The inhibitory effect of tamoxifen on hormone receptor–positive breast cancer is mediated by tamoxifen metabolites, which are catalyzed by the cytochrome P450 2D6 (CYP2D6) enzyme. In a retrospective cohort study of women who received adjuvant tamoxifen for early stage breast cancer, Schroth and colleagues found an association between polymorphisms in CYP2D6 and clinical outcomes. Specifically, women with 2 functional CYP2D6 alleles (“extensive metabolizers”) had a lower risk of recurrence and improved event-free survival and disease-free survival than women with CYP2D6 variants that are associated with reduced or absent enzyme activity.

In an analysis of national data from Britain, Australia, and Canada, Clement and colleagues examined how clinical effectiveness and cost-effectiveness evidence are used by the responsible health care agencies in pharmaceutical coverage decisions. Among the authors' findings was that uncertainty regarding clinical effectiveness—often related to concerns about the quality and strength of the experimental evidence intended to support a clinically meaningful effect—was a key issue in coverage decisions. Other factors considered in drug coverage decisions included the ability to negotiate price, agency processes, and societal values.

In previous work involving healthy iron-replete volunteers, Smith and colleagues found that iron infusion blunted the pulmonary vasoconstrictive response to hypoxia. To assess whether iron availability modifies altitude-induced hypoxic pulmonary hypertension, the investigators conducted 2 randomized, placebo-controlled trials: the first enrolled healthy, sea-level residents who were studied over 1 week of hypoxia at Cerro de Pasco, Peru (altitude, 4340 m), and the second enrolled residents of Cerro de Pasco who had chronic mountain sickness and underwent staged isovolemic venesection to induce iron deficiency. Participants in both studies received intravenous infusion of iron or placebo, and underwent Doppler echocardiography to assess pulmonary artery systolic pressure. The authors found that altitude-induced hypoxic pulmonary hypertension was attenuated by iron supplementation and exacerbated by iron depletion.

Ms Q, a 52-year-old woman with diabetes, has severe lower extremity neuropathic pain that has not responded to a variety of therapies. Rutkove discusses the diagnosis, epidemiology, and treatment of diabetic neuropathy.

“Replaced. How is one's physician, the one who listened, laid hands on, and made clinical judgments, the one entrusted with the intimate details of a life, actually ‘replaced’?” From “Separation Anxiety.”

As the tests available for genetic diseases increase, many organizations, manufacturers, and some government agencies advocate greater regulation.

US Food and Drug Administration regulation of tobacco

Innovation networks and health care transformation

Health reform and mental health and substance abuse services

Disruption and innovation in health care

Join Barbara A. Slade, MD, MS, Wednesday, October 21, from 2 to 3 PM eastern time to discuss postlicensure safety surveillance for the HPV vaccine. To register, go to http://www.ihi.org/AuthorintheRoom.

How would you care for a 66-year-old man with an abdominal aortic aneurysm? Go to www.jama.com to read the case, and submit your response, which may be selected for online publication. Submission deadline is November 8.

For your patients: Information about pulmonary hypertension.

Theme Issue on Advances in Surgery