Karoui, Mehdi; Bucur, Petru Octav
doi: 10.1056/NEJMicm074422pmid: 18832240
This 47-year-old homeless man presented to the emergency department with 1 week of chest pain and a blood count with 27,000 leukocytes per cubic millimeter.
doi: 10.1056/NEJMp0805021pmid: 18832241
The pressures employers face have worsened as health care costs have grown faster than wages. Dr. Robert Galvin writes that although the business community has been a reluctant actor in this arena, it remains skeptical that its interests will be served by solutions arising from the provider community or from increased government control.
doi: 10.1056/NEJMp0806270pmid: 18832242
Many executives take part in one of modern medicine's most expensive and least proven approaches to care: the executive physical. Dr. Brian Rank argues that executive physicals are not good for the patients who undergo them, for the companies that pay for them, or for the health care system overall.
doi: 10.1056/NEJMp0806479pmid: 18832243
By inhibiting the biosynthesis of endogenous cholesterol, the statin drugs lower elevated blood cholesterol levels much more effectively than any dietary or other drug regimen. Dr. Daniel Steinberg describes how statins have revolutionized preventive cardiology.
Gulick, Roy M.; Lalezari, Jacob; Goodrich, James; Clumeck, Nathan; DeJesus, Edwin; Horban, Andrzej; Nadler, Jeffrey; Clotet, Bonaventura; Karlsson, Anders; Wohlfeiler, Michael; Montana, John B.; McHale, Mary; Sullivan, John; Ridgway, Caroline; Felstead, Steve;
Fätkenheuer, Gerd; Nelson, Mark; Lazzarin, Adriano; Konourina, Irina; Hoepelman, Andy I.M.; Lampiris, Harry; Hirschel, Bernard; Tebas, Pablo; Raffi, François; Trottier, Benoit; Bellos, Nicholaos; Saag, Michael; Cooper, David A.; Westby, Mike; Tawadrous, Margaret;
Yang, Zhenglin; Stratton, Charity; Francis, Peter J.; Kleinman, Mark E.; Tan, Perciliz L.; Gibbs, Daniel; Tong, Zongzhong; Chen, Haoyu; Constantine, Ryan; Yang, Xian; Chen, Yuhong; Zeng, Jiexi; Davey, Lisa; Ma, Xiang; Hau, Vincent S.; Wang, Chi;
doi: 10.1056/NEJMoa0805017pmid: 18779236
BackgroundThe value of continuous glucose monitoring in the management of type 1 diabetes mellitus has not been determined.MethodsIn a multicenter clinical trial, we randomly assigned 322 adults and children who were already receiving intensive therapy for type 1 diabetes to a group with continuous glucose monitoring or to a control group performing home monitoring with a blood glucose meter. All the patients were stratified into three groups according to age and had a glycated hemoglobin level of 7.0 to 10.0%. The primary outcome was the change in the glycated hemoglobin level at 26 weeks.ResultsThe changes in glycated hemoglobin levels in the two study groups varied markedly according to age group (P=0.003), with a significant difference among patients 25 years of age or older that favored the continuous-monitoring group (mean difference in change, −0.53%; 95% confidence interval [CI], −0.71 to −0.35; P<0.001). The between-group difference was not significant among those who were 15 to 24 years of age (mean difference, 0.08; 95% CI, −0.17 to 0.33; P=0.52) or among those who were 8 to 14 years of age (mean difference, −0.13; 95% CI, −0.38 to 0.11; P=0.29). Secondary glycated hemoglobin outcomes were better in the continuous-monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference.ConclusionsContinuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents. (ClinicalTrials.gov number, NCT00406133.)
doi: 10.1056/NEJMcp0804458pmid: 18832246
Shortly after being elbowed in the flank during a basketball game, a 35-year-old healthy man has severe, colicky abdominal pain followed by gross hematuria. A renal ultrasound scan reveals bilateral polycystic kidneys and liver cysts. The blood pressure is 160/100 mm Hg. The serum creatinine concentration is 0.9 mg per deciliter (80 μmol per liter). The pain subsides in 2 days with analgesics, rest, and fluids; the gross hematuria resolves in 4 days, although microscopic hematuria persists.
Showing 1 to 10 of 23 Articles
doi: 10.1056/NEJMoa0803152pmid: 18832244
BackgroundCC chemokine receptor 5 antagonists are a new class of antiretroviral agents.MethodsWe conducted two double-blind, placebo-controlled, phase 3 studies — Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 — with patients who had R5 human immunodeficiency virus type 1 (HIV-1) only. They had been treated with or had resistance to three antiretroviral-drug classes and had HIV-1 RNA levels of more than 5000 copies per milliliter. The patients were randomly assigned to one of three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice daily, or placebo, each of which included optimized background therapy (OBT) based on treatment history and drug-resistance testing. Safety and efficacy were assessed after 48 weeks.ResultsA total of 1049 patients received the randomly assigned study drug; the mean baseline HIV-1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48 weeks, in both studies, the mean change in HIV-1 RNA from baseline was greater with maraviroc than with placebo: –1.66 and –1.82 log10 copies per milliliter with the once-daily and twice-daily regimens, respectively, versus –0.80 with placebo in MOTIVATE 1, and –1.72 and –1.87 log10 copies per milliliter, respectively, versus –0.76 with placebo in MOTIVATE 2. More patients receiving maraviroc once or twice daily had HIV-1 RNA levels of less than 50 copies per milliliter (42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE 1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P<0.001 for both comparisons in each study). The change from baseline in CD4 counts was also greater with maraviroc once or twice daily than with placebo (increases of 113 and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of 122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P<0.001 for both comparisons in each study). Frequencies of adverse events were similar among the groups.ConclusionsMaraviroc, as compared with placebo, resulted in significantly greater suppression of HIV-1 and greater increases in CD4 cell counts at 48 weeks in previously treated patients with R5 HIV-1 who were receiving OBT. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)
doi: 10.1056/NEJMoa0803154pmid: 18832245
BackgroundWe conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients.MethodsWe analyzed pooled data from week 48 from the two studies according to sex, race or ethnic group, clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of screening, the use or nonuse of enfuvirtide in optimized background therapy (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs coadministered, the first use of selected background agents, and tropism at baseline. Changes in viral tropism and the CD4 count at treatment failure were evaluated. Data on aminotransferase levels in patients coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) were also analyzed.ResultsA treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline.ConclusionsSubanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)
doi: 10.1056/NEJMoa0802437pmid: 18753640
BackgroundAge-related macular degeneration is the most common cause of irreversible visual impairment in the developed world. Advanced age-related macular degeneration consists of geographic atrophy and choroidal neovascularization. The specific genetic variants that predispose patients to geographic atrophy are largely unknown.MethodsWe tested for an association between the functional toll-like receptor 3 gene (TLR3) variant rs3775291 (involving the substitution of phenylalanine for leucine at amino acid 412) and age-related macular degeneration in Americans of European descent. We also tested for the effect of TLR3 Leu and Phe variants on the viability of human retinal pigment epithelial cells in vitro and on apoptosis of retinal pigment epithelial cells from wild-type mice and Tlr3-knockout (Tlr3−/−) mice.ResultsThe Phe variant (encoded by the T allele at rs3775291) was associated with protection against geographic atrophy (P=0.005). This association was replicated in two independent case–control series of geographic atrophy (P=5.43×10−4 and P=0.002). No association was found between TLR3 variants and choroidal neovascularization. A prototypic TLR3 ligand induced apoptosis in a greater fraction of human retinal pigment epithelial cells with the Leu–Leu genotype than those with the Leu–Phe genotype and in a greater fraction of wild-type mice than Tlr3–/– mice.ConclusionsThe TLR3 412Phe variant confers protection against geographic atrophy, probably by suppressing the death of retinal pigment epithelial cells. Since double-stranded RNA (dsRNA) can activate TLR3-mediated apoptosis, our results suggest a role of viral dsRNA in the development of geographic atrophy and point to the potential toxic effects of short-interfering-RNA therapies in the eye.