The New England Journal of Medicine

Puttarajappa, Chethan; Rajan, Deepa S.

doi: 10.1056/NEJMicm1001091pmid: 20886676

A 72-year-old man presented with a 3-week history of gradually worsening pain and bluish discoloration in his right index, middle, and ring fingers. He was a nonsmoker and reported having had no history of Raynaud's phenomenon, trauma, atrial fibrillation, or any invasive vascular procedure. The physical examination showed bluish discoloration of the distal phalanges and absent ulnar pulse in the right arm. A modified Allen's test was positive (video). Computed tomographic angiography confirmed occlusion of the right ulnar artery. The results of further evaluation with a hypercoagulable workup and transesophageal echocardiography were normal. The patient was treated with antiplatelet agents . . .

Lacroix, Laurence E.; Vunda, Aaron; Bajwa, Nadia M.; Galetto-Lacour, Annick; Gervaix, Alain

doi: 10.1056/NEJMvcm0808873pmid: 20886675

Urethral catheterization may be needed in a child for diagnostic purposes or for performing voiding cystourethrography or monitoring urine output in very ill or postoperative patients. This video demonstrates a diagnostic urethral catheterization in a male infant.

DeKosky, Steven T.; Ikonomovic, Milos D.; Gandy, Sam

doi: 10.1056/NEJMp1007051pmid: 20879875

In late July, the National Football League introduced a new poster to be hung in league locker rooms, warning players of possible long-term health effects of concussions. Public awareness of the pathological consequences of traumatic brain injury has been elevated not only by the recognition of the potential clinical significance of repetitive head injuries in such high-contact sports as American football and boxing, but also by the prevalence of vehicular crashes and efforts to improve passenger safety features, and by modern warfare, especially blast injuries. Each year, more than 1.5 million Americans sustain mild traumatic brain injuries with no loss . . .

Koh, Howard K.; Sebelius, Kathleen G.

doi: 10.1056/NEJMp1008560pmid: 20879876

Too many people in our country are not reaching their full potential for health because of preventable conditions. Moreover, Americans receive only about half of the preventive services that are recommended1 — a finding that highlights the national need for improved health promotion. The 2010 Affordable Care Act2 responds to this need with a vibrant emphasis on disease prevention. Many of the 10 major titles in the law, especially Title IV, Prevention of Chronic Diseases and Improving Public Health, advance a prevention theme through a wide array of new initiatives and funding. As a result, we believe that the Act . . .

Mariner, Wendy K.; Annas, George J.

doi: 10.1056/NEJMp1009054pmid: 20879877

Having been outmaneuvered in Congress with the passage of the Patient Protection and Affordable Care Act (“Affordable Care Act,” or ACA), Republicans have taken their case to federal court, arguing that the law's key provision, the individual mandate to purchase health insurance, is unconstitutional. This argument has been made most prominently by attorneys general from 20 states in a Florida federal court and by the Commonwealth of Virginia in a Virginia federal court. In early August, federal district court judge Henry Hudson decided that the Virginia challenge deserves a hearing,1 thereby giving the constitutional argument an aura of respectability and . . .

doi: 10.1056/NEJMtwj100930pmid: N/A

Weinblatt, Michael E.; Kavanaugh, Arthur; Genovese, Mark C.; Musser, Theresa K.; Grossbard, Elliott B.; Magilavy, Daniel B.

doi: 10.1056/NEJMoa1000500pmid: 20879879

BackgroundSpleen tyrosine kinase (Syk) is an important modulator of immune signaling. The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy.MethodsWe enrolled 457 patients who had active rheumatoid arthritis despite long-term methotrexate therapy in a 6-month, double-blind, placebo-controlled trial. The primary outcome was the American College of Rheumatology (ACR) 20 response (which indicates at least a 20% reduction in the number of both tender and swollen joints and improvement in at least three of five other criteria) at month 6.ResultsR788, at a dose of 100 mg twice daily and at a dose of 150 mg once daily, was significantly superior to placebo at month 6 (ACR 20 response rates of 67% and 57%, respectively, vs. 35%; P<0.001 for the comparison of both doses with placebo). It was also significantly superior with respect to ACR 50, which indicates at least a 50% improvement (43% and 32% vs. 19%; P<0.001 for the comparison of the 100-mg dose with placebo, P=0.007 for the comparison of the 150-mg dose with placebo) and ACR 70 (28% and 14% vs. 10%; P<0.001 for the comparison of the 100-mg dose with placebo, P=0.34 for the comparison of the 150-mg dose with placebo). A clinically significant effect was noted by the end of the first week of treatment. Adverse effects included diarrhea (in 19% of subjects taking the 100-mg dose of R788 vs. 3% of those taking placebo), upper respiratory infections (14% vs. 7%), and neutropenia (6% vs. 1%). R788 was associated with an increase in systolic blood pressure of approximately 3 mm Hg between baseline and month 1, as compared with a decrease of 2 mm Hg with placebo; 23% of the patients taking R788 vs. 7% of the patients receiving placebo required the initiation of or a change in antihypertensive therapy.ConclusionsIn this phase 2 study, a Syk inhibitor reduced disease activity in patients with rheumatoid arthritis; adverse events included diarrhea, hypertension, and neutropenia. Additional studies will be needed to further assess the safety and efficacy of Syk-inhibition therapy in patients with rheumatoid arthritis. (Funded by Rigel; ClinicalTrials.gov number, NCT00665925.)

Baker, David L.; Schmidt, Mary L.; Cohn, Susan L.; Maris, John M.; London, Wendy B.; Buxton, Allen; Stram, Daniel; Castleberry, Robert P.; Shimada, Hiroyuki; Sandler, Anthony; Shamberger, Robert C.; Look, A. Thomas; Reynolds, C. Patrick; Seeger, Robert C.; Matthay, Katherine K.

Yu, Alice L.; Gilman, Andrew L.; Ozkaynak, M. Fevzi; London, Wendy B.; Kreissman, Susan G.; Chen, Helen X.; Smith, Malcolm; Anderson, Barry; Villablanca, Judith G.; Matthay, Katherine K.; Shimada, Hiro; Grupp, Stephan A.; Seeger, Robert; Reynolds, C. Patrick; Buxton, Allen;

Vadlamudi, Lata; Dibbens, Leanne M.; Lawrence, Kate M.; Iona, Xenia; McMahon, Jacinta M.; Murrell, Wayne; Mackay-Sim, Alan; Scheffer, Ingrid E.; Berkovic, Samuel F.

doi: 10.1056/NEJMoa0910752pmid: 20879882

De novo mutations are a cause of sporadic disease, but little is known about the developmental timing of such mutations. We studied concordant and discordant monozygous twins with de novo mutations in the sodium channel α1 subunit gene (SCN1A) causing Dravet's syndrome, a severe epileptic encephalopathy. On the basis of our findings and the literature on mosaic cases, we conclude that de novo mutations in SCN1A may occur at any time, from the premorula stage of the embryo (causing disease in the subject) to adulthood (with mutations in the germ-line cells of parents causing disease in offspring).