Navigating the Choices for Diabetes Prevention.

N Engl J Med. 2010 Mar 14;

Authors: Nathan DM

PMID: 20228400 [PubMed - as supplied by publisher]

ACCORD and Risk-Factor Control in Type 2 Diabetes.

N Engl J Med. 2010 Mar 14;

Authors: Nilsson PM

PMID: 20228405 [PubMed - as supplied by publisher]

Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus.

N Engl J Med. 2010 Mar 14;

Authors:

BACKGROUND: We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. METHODS: We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS: The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction). CONCLUSIONS: The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) Copyright 2010 Massachusetts Medical Society.

PMID: 20228404 [PubMed - as supplied by publisher]

Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events.

N Engl J Med. 2010 Mar 16;

Authors:

BACKGROUND: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.) Copyright 2010 Massachusetts Medical Society.

PMID: 20228403 [PubMed - as supplied by publisher]

Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events.

N Engl J Med. 2010 Mar 14;

Authors:

BACKGROUND: The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS: In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS: After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.) Copyright 2010 Massachusetts Medical Society.

PMID: 20228402 [PubMed - as supplied by publisher]

Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus.

N Engl J Med. 2010 Mar 14;

Authors:

BACKGROUND: There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events. METHODS: A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS: After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P=0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI 0.85 to 1.35; P=0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001). CONCLUSIONS: In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.) Copyright 2010 Massachusetts Medical Society.

PMID: 20228401 [PubMed - as supplied by publisher]

Duration of Dual Antiplatelet Therapy after Implantation of Drug-Eluting Stents.

N Engl J Med. 2010 Mar 15;

Authors: Park SJ, Park DW, Kim YH, Kang SJ, Lee SW, Lee CW, Han KH, Park SW, Yun SC, Lee SG, Rha SW, Seong IW, Jeong MH, Hur SH, Lee NH, Yoon J, Yang JY, Lee BK, Choi YJ, Chung WS, Lim DS, Cheong SS, Kim KS, Chae JK, Nah DY, Jeon DS, Seung KB, Jang JS, Park HS, Lee K

BACKGROUND: The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established. METHODS: In two trials, we randomly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis. RESULTS: The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval [CI], 0.80 to 3.36; P=0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P=0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P=0.06). CONCLUSIONS: The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.) Copyright 2010 Massachusetts Medical Society.

PMID: 20231231 [PubMed - as supplied by publisher]

Optimal Duration of Clopidogrel Use after Implantation of Drug-Eluting Stents -- Still in Doubt.

N Engl J Med. 2010 Mar 15;

Authors: Berger PB

PMID: 20231230 [PubMed - as supplied by publisher]

Lenient versus Strict Rate Control in Patients with Atrial Fibrillation.

N Engl J Med. 2010 Mar 15;

Authors: Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van Veldhuisen DJ, Van den Berg MP,

BACKGROUND: Rate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation. METHODS: We randomly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate <110 beats per minute) or a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. The duration of follow-up was at least 2 years, with a maximum of 3 years. RESULTS: The estimated cumulative incidence of the primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group, with an absolute difference with respect to the lenient-control group of -2.0 percentage points (90% confidence interval, -7.6 to 3.5; P<0.001 for the prespecified noninferiority margin). The frequencies of the components of the primary outcome were similar in the two groups. More patients in the lenient-control group met the heart-rate target or targets (304 [97.7%], vs. 203 [67.0%] in the strict-control group; P<0.001) with fewer total visits (75 [median, 0], vs. 684 [median, 2]; P<0.001). The frequencies of symptoms and adverse events were similar in the two groups. CONCLUSIONS: In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613.) Copyright 2010 Massachusetts Medical Society.

PMID: 20231232 [PubMed - as supplied by publisher]

Rate Control in Atrial Fibrillation.

N Engl J Med. 2010 Mar 15;

Authors: Dorian P

PMID: 20231233 [PubMed - as supplied by publisher]

Stem-cell transplantation for sickle cell disease.

N Engl J Med. 2010 Mar 11;362(10):955-6; author reply 956

Authors: Walters MC, Sullivan KM

PMID: 20225347 [PubMed - in process]

Insulin regimens in type 2 diabetes.

N Engl J Med. 2010 Mar 11;362(10):959-60; author reply 960

Authors: Margolis KL, O'Connor PJ, Sperl-Hillen JM

PMID: 20225350 [PubMed - in process]

Biventricular pacing.

N Engl J Med. 2010 Mar 11;362(10):957-8; author reply 958-9

Authors: Lim HS

PMID: 20225349 [PubMed - in process]

Biventricular pacing.

N Engl J Med. 2010 Mar 11;362(10):957; author reply 958-9

Authors: Tomoda H

PMID: 20225348 [PubMed - in process]

Insulin regimens in type 2 diabetes.

N Engl J Med. 2010 Mar 11;362(10):960; author reply 960

Authors: Cordido F

PMID: 20225351 [PubMed - in process]

How to Think about Future Health Care Spending.

N Engl J Med. 2010 Mar 10;

Authors: Fuchs VR

PMID: 20220179 [PubMed - as supplied by publisher]

Individual Genomes on the Horizon.

N Engl J Med. 2010 Mar 10;

Authors: Lifton RP

PMID: 20220178 [PubMed - as supplied by publisher]

Whole-Genome Sequencing in a Patient with Charcot-Marie-Tooth Neuropathy.

N Engl J Med. 2010 Mar 10;

Authors: Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA

BACKGROUND: Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot-Marie-Tooth disease. METHODS: We identified a family with a recessive form of Charcot-Marie-Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members. RESULTS: We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot-Marie-Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome. CONCLUSIONS: As shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients. Copyright 2010 Massachusetts Medical Society.

PMID: 20220177 [PubMed - as supplied by publisher]

Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.

N Engl J Med. 2010 Mar 11;362(10):875-85

Authors: Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, Gascoyne RD

BACKGROUND: Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score. METHODS: Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis. RESULTS: Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P=0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P=0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P=0.008), resulting in shortened disease-specific survival (P=0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P=0.003 vs. P=0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies. CONCLUSIONS: An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.

PMID: 20220182 [PubMed - in process]

The missing voice of patients in drug-safety reporting.

N Engl J Med. 2010 Mar 11;362(10):865-9

Authors: Basch E

PMID: 20220181 [PubMed - in process]

Images in clinical medicine. Dermoscopy of phthiriasis.

N Engl J Med. 2010 Mar 11;362(10):e33

Authors: DeFazio JL, Spencer P

PMID: 20220180 [PubMed - in process]

Oral ivermectin versus malathion lotion for difficult-to-treat head Lice.

N Engl J Med. 2010 Mar 11;362(10):896-905

Authors: Chosidow O, Giraudeau B, Cottrell J, Izri A, Hofmann R, Mann SG, Burgess I

BACKGROUND: Head-lice infestation is prevalent worldwide, especially in children 3 to 11 years old. Topical insecticides (i.e., pyrethroids and malathion) used as a lotion, applied twice at an interval of 7 to 11 days, are typically used for treatment. Resistance of lice to insecticides, particularly pyrethroids, results in treatment failure. The efficacy of alternative agents is controversial. METHODS: We conducted a multicenter, cluster-randomized, double-blind, double-dummy, controlled trial comparing oral ivermectin (at a dose of 400 microg per kilogram of body weight) with 0.5% malathion lotion, each given on days 1 and 8, for patients with live lice not eradicated by topical insecticide used 2 to 6 weeks before enrollment. The cluster was defined as the household. Infestation was confirmed and monitored by means of fine-toothed combing. Patients were at least 2 years of age and weighed at least 15 kg; all were treated at the study sites. The primary end point was the absence of head lice on day 15. RESULTS: A total of 812 patients from 376 households were randomly assigned to receive either ivermectin or malathion. In the intention-to-treat population, 95.2% of patients receiving ivermectin were lice-free on day 15, as compared with 85.0% of those receiving malathion (absolute difference, 10.2 percentage points; 95% confidence interval [CI], 4.6 to 15.7; P<0.001). In the per-protocol population, 97.1% of patients in the ivermectin group were lice-free on day 15, as compared with 89.8% of those in the malathion group (absolute difference, 7.3 percentage points; 95% CI, 2.8 to 11.8; P=0.002). There were no significant differences in the frequencies of adverse events between the two treatment groups. CONCLUSIONS: For difficult-to-treat head-lice infestation, oral ivermectin, given twice at a 7-day interval, had superior efficacy as compared with topical 0.5% malathion lotion, a finding that suggests that it could be an alternative treatment. (ClinicalTrials.gov number, NCT00819520.)

PMID: 20220184 [PubMed - in process]

Low diagnostic yield of elective coronary angiography.

N Engl J Med. 2010 Mar 11;362(10):886-95

Authors: Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, Brindis RG, Douglas PS

BACKGROUND: Guidelines for triaging patients for cardiac catheterization recommend a risk assessment and noninvasive testing. We determined patterns of noninvasive testing and the diagnostic yield of catheterization among patients with suspected coronary artery disease in a contemporary national sample. METHODS: From January 2004 through April 2008, at 663 hospitals in the American College of Cardiology National Cardiovascular Data Registry, we identified patients without known coronary artery disease who were undergoing elective catheterization. The patients' demographic characteristics, risk factors, and symptoms and the results of noninvasive testing were correlated with the presence of obstructive coronary artery disease, which was defined as stenosis of 50% or more of the diameter of the left main coronary artery or stenosis of 70% or more of the diameter of a major epicardial vessel. RESULTS: A total of 398,978 patients were included in the study. The median age was 61 years; 52.7% of the patients were men, 26.0% had diabetes, and 69.6% had hypertension. Noninvasive testing was performed in 83.9% of the patients. At catheterization, 149,739 patients (37.6%) had obstructive coronary artery disease. No coronary artery disease (defined as <20% stenosis in all vessels) was reported in 39.2% of the patients. Independent predictors of obstructive coronary artery disease included male sex (odds ratio, 2.70; 95% confidence interval [CI], 2.64 to 2.76), older age (odds ratio per 5-year increment, 1.29; 95% CI, 1.28 to 1.30), presence of insulin-dependent diabetes (odds ratio, 2.14; 95% CI, 2.07 to 2.21), and presence of dyslipidemia (odds ratio, 1.62; 95% CI, 1.57 to 1.67). Patients with a positive result on a noninvasive test were moderately more likely to have obstructive coronary artery disease than those who did not undergo any testing (41.0% vs. 35.0%; P<0.001; adjusted odds ratio, 1.28; 95% CI, 1.19 to 1.37). CONCLUSIONS: In this study, slightly more than one third of patients without known disease who underwent elective cardiac catheterization had obstructive coronary artery disease. Better strategies for risk stratification are needed to inform decisions and to increase the diagnostic yield of cardiac catheterization in routine clinical practice.

PMID: 20220183 [PubMed - in process]

Commotio cordis.

N Engl J Med. 2010 Mar 11;362(10):917-27

Authors: Maron BJ, Estes NA

PMID: 20220186 [PubMed - in process]

Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia.

N Engl J Med. 2010 Mar 11;362(10):906-16

Authors: Ladenson PW, Kristensen JD, Ridgway EC, Olsson AG, Carlsson B, Klein I, Baxter JD, Angelin B

BACKGROUND: Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormone lowers levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided. METHODS: We performed a randomized, placebo-controlled, double-blind, multicenter trial to assess the safety and efficacy of the thyromimetic compound eprotirome (KB2115) in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. In addition to statin treatment, patients received either eprotirome (at a dose of 25, 50, or 100 microg per day) or placebo. Secondary outcomes were changes in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Patients were monitored for potential adverse thyromimetic effects on the heart, bone, and pituitary. RESULTS: The addition of placebo or eprotirome at a dose of 25, 50, or 100 microg daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome. CONCLUSIONS: In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins. (ClinicalTrials.gov number, NCT00593047.)

PMID: 20220185 [PubMed - in process]

Toward a personalized treatment of Hodgkin's disease.

N Engl J Med. 2010 Mar 11;362(10):942-3

Authors: DeVita VT, Costa J

PMID: 20220189 [PubMed - in process]

Case records of the Massachusetts General Hospital. Case 7-2010. A 49-year-old man with peripheral neuropathy and ascites.

N Engl J Med. 2010 Mar 11;362(10):929-40

Authors: Ropper AH, Raje NS, Lawrimore TM, Camelo-Piragua S, Sohani AR

PMID: 20220188 [PubMed - in process]

Images in clinical medicine. Red puffy ears.

N Engl J Med. 2010 Mar 11;362(10):928

Authors: Kawai H, Nakajima A

PMID: 20220187 [PubMed - in process]

Clinical decisions. American Board of Internal Medicine maintenance of certification program.

N Engl J Med. 2010 Mar 11;362(10):948-52

Authors: Levinson W, King TE, Goldman L, Goroll AH, Kessler B

PMID: 20220192 [PubMed - in process]

Considering recertification.

N Engl J Med. 2010 Mar 11;362(10):946-7

Authors: Drazen JM, Weinstein DF

PMID: 20220191 [PubMed - in process]

Medical imaging in the 21st century--getting the best bang for the rad.

N Engl J Med. 2010 Mar 11;362(10):943-5

Authors: Brenner DJ

PMID: 20220190 [PubMed - in process]

Biventricular pacing.

N Engl J Med. 2010 Mar 11;362(10):956-7; author reply 958-9

Authors: McEvoy JW

PMID: 20220195 [PubMed - in process]

Stem-cell transplantation for sickle cell disease.

N Engl J Med. 2010 Mar 11;362(10):955; author reply 956

Authors: Dew A, van Besien K

PMID: 20220194 [PubMed - in process]

Ameliorating amyotrophic lateral sclerosis.

N Engl J Med. 2010 Mar 11;362(10):953-4

Authors: Rowland LP

PMID: 20220193 [PubMed - in process]

Case 36-2009: A man with cough, hoarseness, and abnormalities on chest imaging.

N Engl J Med. 2010 Mar 11;362(10):961; author reply 961

Authors: Subbiah V

PMID: 20220197 [PubMed - in process]

Insulin regimens in type 2 diabetes.

N Engl J Med. 2010 Mar 11;362(10):959; author reply 960

Authors: Lund SS, Vaag AA

PMID: 20220196 [PubMed - in process]

Imaging in early-stage Hodgkin's lymphoma.

N Engl J Med. 2010 Mar 11;362(10):962

Authors: Juweid ME, Vose JM

PMID: 20220198 [PubMed - in process]

On-pump versus off-pump CABG.

N Engl J Med. 2010 Mar 4;362(9):852; author reply 853-4

Authors: Taggart DP

PMID: 20213877 [PubMed - indexed for MEDLINE]

On-pump versus off-pump CABG.

N Engl J Med. 2010 Mar 4;362(9):852-3; author reply 853-4

Authors: Caplan LR

PMID: 20213880 [PubMed - indexed for MEDLINE]

On-pump versus off-pump CABG.

N Engl J Med. 2010 Mar 4;362(9):852; author reply 853-4

Authors: Augoustides JG

PMID: 20213879 [PubMed - indexed for MEDLINE]

On-pump versus off-pump CABG.

N Engl J Med. 2010 Mar 4;362(9):852; author reply 853-4

Authors: Kieser TM

PMID: 20213878 [PubMed - indexed for MEDLINE]

A controlled trial of initial antiviral regimens for HIV-1 infection.

N Engl J Med. 2010 Mar 4;362(9):854-5; author reply 855

Authors: Leiner S

PMID: 20213882 [PubMed - indexed for MEDLINE]

Revascularization for renal-artery stenosis.

N Engl J Med. 2010 Feb 25;362(8):762-3; author reply 763-4

Authors: Esposito P, Piotti G, Dal Canton A

PMID: 20191667 [PubMed - in process]

A novel antibody associated with autoimmune pancreatitis.

N Engl J Med. 2010 Feb 25;362(8):759-60; author reply 760-1

Authors: Park do H, Hwang JY, Kim MH

PMID: 20191666 [PubMed - in process]

A novel antibody associated with autoimmune pancreatitis.

N Engl J Med. 2010 Feb 25;362(8):759; author reply 760-1

Authors: Wang CC, Kao JH

PMID: 20191665 [PubMed - in process]

Management of lung nodules detected by volume CT scanning.

N Engl J Med. 2010 Feb 25;362(8):757-8; author reply 758-9

Authors: Bölükbas S, Eberlein M, Schirren J

PMID: 20191664 [PubMed - in process]

Revascularization for renal-artery stenosis.

N Engl J Med. 2010 Feb 25;362(8):763; author reply 763-4

Authors: Mills NL, Dhaun N, Uren NG

PMID: 20191669 [PubMed - in process]

Revascularization for renal-artery stenosis.

N Engl J Med. 2010 Feb 25;362(8):762; author reply 763-4

Authors: Wilentz JR

PMID: 20191668 [PubMed - in process]

The Democrats' Last Ditch -- Reconciliation or Bust.

N Engl J Med. 2010 Mar 3;

Authors: Iglehart JK

PMID: 20200360 [PubMed - as supplied by publisher]

Haitian Amputees -- Lessons Learned from Sierra Leone.

N Engl J Med. 2010 Mar 3;

Authors: Kelly JD

PMID: 20200359 [PubMed - as supplied by publisher]

Choosing Asthma Step-up Care.

N Engl J Med. 2010 Mar 3;

Authors: von Mutius E, Drazen JM

PMID: 20197426 [PubMed - as supplied by publisher]

Step-up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids.

N Engl J Med. 2010 Mar 3;

Authors: Lemanske RF, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Covar RA, Guilbert TW, Larsen G, Morgan WJ, Moss MH, Spahn JD, Taussig LM,

BACKGROUND: For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking. METHODS: We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 mug of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 mug of fluticasone twice daily (ICS step-up), 100 mug of fluticasone plus 50 mug of a long-acting beta-agonist twice daily (LABA step-up), or 100 mug of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%. RESULTS: A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005). CONCLUSIONS: Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.) Copyright 2010 Massachusetts Medical Society.

PMID: 20197425 [PubMed - as supplied by publisher]

Haiti -- A View from the Ship.

N Engl J Med. 2010 Mar 3;

Authors: Curran M

PMID: 20200363 [PubMed - as supplied by publisher]

The Israeli Field Hospital in Haiti -- Ethical Dilemmas in Early Disaster Response.

N Engl J Med. 2010 Mar 3;

Authors: Merin O, Ash N, Levy G, Schwaber MJ, Kreiss Y

PMID: 20200362 [PubMed - as supplied by publisher]

Ministry of Touch -- Reflections on Disaster Work after the Haitian Earthquake.

N Engl J Med. 2010 Mar 3;

Authors: Goodman A

PMID: 20200361 [PubMed - as supplied by publisher]

Medicare's opportunity to encourage innovation in health care delivery.

N Engl J Med. 2010 Mar 4;362(9):772-4

Authors: Mechanic R, Altman S

PMID: 20200381 [PubMed - in process]

Images in clinical medicine. Neuropathic ulceration.

N Engl J Med. 2010 Mar 4;362(9):e26

Authors: Teelucksingh S, Naraynsingh V

PMID: 20200380 [PubMed - in process]

Health Care Reform -- Where Do We Go from Here?

N Engl J Med. 2010 Mar 3;

Authors: Wilensky GR

PMID: 20200364 [PubMed - as supplied by publisher]

Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy.

N Engl J Med. 2010 Mar 4;362(9):790-9

Authors: Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO, Capparelli EV, Adamson PC,

BACKGROUND: Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined. METHODS: In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons. RESULTS: The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03). CONCLUSIONS: Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)

PMID: 20200383 [PubMed - in process]

Comparison of dopamine and norepinephrine in the treatment of shock.

N Engl J Med. 2010 Mar 4;362(9):779-89

Authors: De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL,

BACKGROUND: Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS: In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS: The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses). CONCLUSIONS: Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)

PMID: 20200382 [PubMed - in process]

Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults.

N Engl J Med. 2010 Mar 4;362(9):800-11

Authors: Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, Coresh J, Brancati FL

BACKGROUND: Fasting glucose is the standard measure used to diagnose diabetes in the United States. Recently, glycated hemoglobin was also recommended for this purpose. METHODS: We compared the prognostic value of glycated hemoglobin and fasting glucose for identifying adults at risk for diabetes or cardiovascular disease. We measured glycated hemoglobin in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990-1992 period) of the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios (with 95% confidence intervals) for diagnosed diabetes were 0.52 (0.40 to 0.69), 1.00 (reference), 1.86 (1.67 to 2.08), 4.48 (3.92 to 5.13), and 16.47 (14.22 to 19.08), respectively. For coronary heart disease, the hazard ratios were 0.96 (0.74 to 1.24), 1.00 (reference), 1.23 (1.07 to 1.41), 1.78 (1.48 to 2.15), and 1.95 (1.53 to 2.48), respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose. CONCLUSIONS: In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.

PMID: 20200384 [PubMed - in process]

Management of varices and variceal hemorrhage in cirrhosis.

N Engl J Med. 2010 Mar 4;362(9):823-32

Authors: Garcia-Tsao G, Bosch J

PMID: 20200386 [PubMed - in process]

A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults.

N Engl J Med. 2010 Mar 4;362(9):812-22

Authors: French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF

BACKGROUND: Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed. METHODS: In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A. RESULTS: From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P=0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P=0.003). CONCLUSIONS: The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731.)

PMID: 20200385 [PubMed - in process]

Clinical problem-solving. Stalking the diagnosis.

N Engl J Med. 2010 Mar 4;362(9):834-9

Authors: Chamarthi B, Morris CA, Kaiser UB, Katz JT, Loscalzo J

PMID: 20200388 [PubMed - in process]

Images in clinical medicine. Congenital cytomegalovirus infection.

N Engl J Med. 2010 Mar 4;362(9):833

Authors: Abdel-Latif Mel-A, Sugo E

PMID: 20200387 [PubMed - in process]

Collection of data on patients' race and ethnic group by physician practices.

N Engl J Med. 2010 Mar 4;362(9):846-50

Authors: Wynia MK, Ivey SL, Hasnain-Wynia R

PMID: 20200391 [PubMed - in process]

Ethosuximide in childhood absence epilepsy--older and better.

N Engl J Med. 2010 Mar 4;362(9):843-5

Authors: Vining EP

PMID: 20200390 [PubMed - in process]

Treating shock--old drugs, new ideas.

N Engl J Med. 2010 Mar 4;362(9):841-3

Authors: Levy JH

PMID: 20200389 [PubMed - in process]

A controlled trial of initial antiviral regimens for HIV-1 infection.

N Engl J Med. 2010 Mar 4;362(9):854; author reply 855

Authors: Parienti JJ

PMID: 20200393 [PubMed - in process]

On-pump versus off-pump CABG.

N Engl J Med. 2010 Mar 4;362(9):851; author reply 853-4

Authors: Puskas JD, Mack MJ, Smith CR

PMID: 20200392 [PubMed - in process]

A crisis in late pregnancy.

N Engl J Med. 2010 Mar 4;362(9):857; author reply 858

Authors: Hancock EW

PMID: 20200395 [PubMed - in process]

Effects of obesity and smoking on U.S. life expectancy.

N Engl J Med. 2010 Mar 4;362(9):855-6; author reply 856-7

Authors: Peto R, Whitlock G, Jha P

PMID: 20200394 [PubMed - in process]

Capecitabine and oxaliplatin for advanced esophagogastric cancer.

N Engl J Med. 2010 Mar 4;362(9):858-9

Authors: Cunningham D, Okines AF, Ashley S

PMID: 20200397 [PubMed - in process]

Repair of mitral-valve prolapse.

N Engl J Med. 2010 Mar 4;362(9):857

Authors: Bouzas-Mosquera A, Alvarez-Garcia N, Peteiro J

PMID: 20200396 [PubMed - in process]

Surveys of physicians and electronic health information.

N Engl J Med. 2010 Mar 4;362(9):859-60

Authors: Hesse BW, Moser RP, Rutten LJ

PMID: 20200398 [PubMed - in process]

Darbepoetin alfa and chronic kidney disease.

N Engl J Med. 2010 Feb 18;362(7):654-5; author reply 655

Authors: Locatelli F, Del Vecchio L, Casartelli D

PMID: 20187259 [PubMed - in process]

Darbepoetin alfa and chronic kidney disease.

N Engl J Med. 2010 Feb 18;362(7):653-4; author reply 655

Authors: Minnerup J, Schäbitz WR

PMID: 20187258 [PubMed - in process]

Thiazide diuretics.

N Engl J Med. 2010 Feb 18;362(7):659-60; author reply 660

Authors: Smith SM

PMID: 20187262 [PubMed - in process]

Rasagiline in Parkinson's disease.

N Engl J Med. 2010 Feb 18;362(7):658; author reply 658-9

Authors: Schwarzschild MA

PMID: 20187261 [PubMed - in process]

Darbepoetin alfa and chronic kidney disease.

N Engl J Med. 2010 Feb 18;362(7):654; author reply 655

Authors: Hampl H, Kovesdy CP, Kalantar-Zadeh K

PMID: 20187260 [PubMed - in process]

Market exclusivity for biologics.

N Engl J Med. 2010 Feb 18;362(7):661; author reply 661-2

Authors: Pollock A, Zagari M

PMID: 20187263 [PubMed - in process]

Civil-Military Collaboration in the Initial Medical Response to the Earthquake in Haiti.

N Engl J Med. 2010 Feb 24;

Authors: Auerbach PS, Norris RL, Menon AS, Brown IP, Kuah S, Schwieger J, Kinyon J, Helderman TN, Lawry L

PMID: 20181962 [PubMed - as supplied by publisher]

Be Not Afraid.

N Engl J Med. 2010 Feb 24;

Authors: Nichols LM

PMID: 20181965 [PubMed - as supplied by publisher]

The FDA and Safe Use of Long-Acting Beta-Agonists in the Treatment of Asthma.

N Engl J Med. 2010 Feb 24;

Authors: Chowdhury BA, Dal Pan G

PMID: 20181964 [PubMed - as supplied by publisher]

Rapid Medical Relief -- Project Medishare and the Haitian Earthquake.

N Engl J Med. 2010 Feb 25;

Authors: Ginzburg E, O'Neill WW, Goldschmidt-Clermont PJ, de Marchena E, Pust D, Green BA

PMID: 20181963 [PubMed - as supplied by publisher]

Serving two masters--conflicts of interest in academic medicine.

N Engl J Med. 2010 Feb 25;362(8):669-71

Authors: Lo B

PMID: 20181969 [PubMed - in process]

Images in clinical medicine. Abdominal-wall abscess.

N Engl J Med. 2010 Feb 25;362(8):e24

Authors: Rajagopalan S, Loudon M

PMID: 20181968 [PubMed - in process]

Can States Pick Up the Health Reform Torch?

N Engl J Med. 2010 Feb 25;

Authors: Rosenbaum S

PMID: 20181967 [PubMed - as supplied by publisher]

Health Care Volunteers and Disaster Response -- First, Be Prepared.

N Engl J Med. 2010 Feb 24;

Authors: Merchant RM, Leigh JE, Lurie N

PMID: 20181966 [PubMed - as supplied by publisher]

Timing of initiation of antiretroviral drugs during tuberculosis therapy.

N Engl J Med. 2010 Feb 25;362(8):697-706

Authors: Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, Gengiah T, Nair G, Bamber S, Singh A, Khan M, Pienaar J, El-Sadr W, Friedland G, Abdool Karim Q

BACKGROUND: The rates of death are high among patients with coinfection with tuberculosis and the human immunodeficiency virus (HIV). The optimal timing for the initiation of antiretroviral therapy in relation to tuberculosis therapy remains controversial. METHODS: In an open-label, randomized, controlled trial in Durban, South Africa, we assigned 642 patients with both tuberculosis and HIV infection to start antiretroviral therapy either during tuberculosis therapy (in two integrated-therapy groups) or after the completion of such treatment (in one sequential-therapy group). The diagnosis of tuberculosis was based on a positive sputum smear for acid-fast bacilli. Only patients with HIV infection and a CD4+ cell count of less than 500 per cubic millimeter were included. All patients received standard tuberculosis therapy, prophylaxis with trimethoprim-sulfamethoxazole, and a once-daily antiretroviral regimen of didanosine, lamivudine, and efavirenz. The primary end point was death from any cause. RESULTS: This analysis compares data from the sequential-therapy group and the combined integrated-therapy groups up to September 1, 2008, when the data and safety monitoring committee recommended that all patients receive integrated antiretroviral therapy. There was a reduction in the rate of death among the 429 patients in the combined integrated-therapy groups (5.4 deaths per 100 person-years, or 25 deaths), as compared with the 213 patients in the sequential-therapy group (12.1 per 100 person-years, or 27 deaths); a relative reduction of 56% (hazard ratio in the combined integrated-therapy groups, 0.44; 95% confidence interval, 0.25 to 0.79; P=0.003). Mortality was lower in the combined integrated-therapy groups in all CD4+ count strata. Rates of adverse events during follow-up were similar in the two study groups. CONCLUSIONS: The initiation of antiretroviral therapy during tuberculosis therapy significantly improved survival and provides further impetus for the integration of tuberculosis and HIV services. (ClinicalTrials.gov number, NCT00398996.)

PMID: 20181971 [PubMed - in process]

Lasofoxifene in postmenopausal women with osteoporosis.

N Engl J Med. 2010 Feb 25;362(8):686-96

Authors: Cummings SR, Ensrud K, Delmas PD, LaCroix AZ, Vukicevic S, Reid DM, Goldstein S, Sriram U, Lee A, Thompson J, Armstrong RA, Thompson DD, Powles T, Zanchetta J, Kendler D, Neven P, Eastell R,

BACKGROUND: The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascular disease are uncertain. METHODS: In this randomized trial, we assigned 8556 women who were between the ages of 59 and 80 years and had a bone mineral density T score of -2.5 or less at the femoral neck or spine to receive once-daily lasofoxifene (at a dose of either 0.25 mg or 0.5 mg) or placebo for 5 years. Primary end points were vertebral fractures, estrogen receptor (ER)-positive breast cancer, and nonvertebral fractures; secondary end points included major coronary heart disease events and stroke. RESULTS: Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1000 person-years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 person-years; hazard ratio, 0.19; 95% CI, 0.07 to 0.56), coronary heart disease events (5.1 vs. 7.5 cases per 1000 person-years; hazard ratio, 0.68; 95% CI, 0.50 to 0.93), and stroke (2.5 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.64; 95% CI, 0.41 to 0.99). Lasofoxifene at a dose of 0.25 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (16.0 vs. 22.4 cases per 1000 person-years; hazard ratio, 0.69; 95% CI, 0.57 to 0.83) and stroke (2.4 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.61; 95% CI, 0.39 to 0.96) Both the lower and higher doses, as compared with placebo, were associated with an increase in venous thromboembolic events (3.8 and 2.9 cases vs. 1.4 cases per 1000 person-years; hazard ratios, 2.67 [95% CI, 1.55 to 4.58] and 2.06 [95% CI, 1.17 to 3.60], respectively). Endometrial cancer occurred in three women in the placebo group, two women in the lower-dose lasofoxifene group, and two women in the higher-dose lasofoxifene group. Rates of death per 1000 person-years were 5.1 in the placebo group, 7.0 in the lower-dose lasofoxifene group, and 5.7 in the higher-dose lasofoxifene group. CONCLUSIONS: In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events. (ClinicalTrials.gov number, NCT00141323.)

PMID: 20181970 [PubMed - in process]

Graves' ophthalmopathy.

N Engl J Med. 2010 Feb 25;362(8):726-38

Authors: Bahn RS

PMID: 20181974 [PubMed - in process]

Permethrin and ivermectin for scabies.

N Engl J Med. 2010 Feb 25;362(8):717-25

Authors: Currie BJ, McCarthy JS

PMID: 20181973 [PubMed - in process]

An algorithm for tuberculosis screening and diagnosis in people with HIV.

N Engl J Med. 2010 Feb 25;362(8):707-16

Authors: Cain KP, McCarthy KD, Heilig CM, Monkongdee P, Tasaneeyapan T, Kanara N, Kimerling ME, Chheng P, Thai S, Sar B, Phanuphak P, Teeratakulpisarn N, Phanuphak N, Nguyen HD, Hoang TQ, Le HT, Varma JK

BACKGROUND: Tuberculosis screening is recommended for people with human immunodeficiency virus (HIV) infection to facilitate early diagnosis and safe initiation of antiretroviral therapy and isoniazid preventive therapy. No internationally accepted, evidence-based guideline addresses the optimal means of conducting such screening, although screening for chronic cough is common. METHODS: We consecutively enrolled people with HIV infection from eight outpatient clinics in Cambodia, Thailand, and Vietnam. For each patient, three samples of sputum and one each of urine, stool, blood, and lymph-node aspirate (for patients with lymphadenopathy) were obtained for mycobacterial culture. We compared the characteristics of patients who received a diagnosis of tuberculosis (on the basis of having one or more specimens that were culture-positive) with those of patients who did not have tuberculosis to derive an algorithm for screening and diagnosis. RESULTS: Tuberculosis was diagnosed in 267 (15%) of 1748 patients (median CD4+ T-lymphocyte count, 242 per cubic millimeter; interquartile range, 82 to 396). The presence of a cough for 2 or 3 weeks or more during the preceding 4 weeks had a sensitivity of 22 to 33% for detecting tuberculosis. The presence of cough of any duration, fever of any duration, or night sweats lasting 3 or more weeks in the preceding 4 weeks was 93% sensitive and 36% specific for tuberculosis. In the 1199 patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph, and a CD4+ cell count of 350 or more per cubic millimeter helped to rule out a diagnosis of tuberculosis, whereas a positive diagnosis could be made only for the 113 patients (9%) with one or more positive sputum smears; mycobacterial culture was required for most other patients. CONCLUSIONS: In persons with HIV infection, screening for tuberculosis should include asking questions about a combination of symptoms rather than only about chronic cough. It is likely that antiretroviral therapy and isoniazid preventive therapy can be started safely in people whose screening for all three symptoms is negative, whereas diagnosis in most others will require mycobacterial culture.

PMID: 20181972 [PubMed - in process]

Another selective estrogen-receptor modulator for osteoporosis.

N Engl J Med. 2010 Feb 25;362(8):752-4

Authors: Becker C

PMID: 20181977 [PubMed - in process]

Case records of the Massachusetts General Hospital. Case 6-2010. A 37-year-old man with a lesion on the tongue.

N Engl J Med. 2010 Feb 25;362(8):740-8

Authors: Flynn TR, Hunter GJ, Johnson MM

PMID: 20181976 [PubMed - in process]

Images in clinical medicine. Processus supracondylaris humeri.

N Engl J Med. 2010 Feb 25;362(8):739

Authors: Billmann F

PMID: 20181975 [PubMed - in process]

Management of lung nodules detected by volume CT scanning.

N Engl J Med. 2010 Feb 25;362(8):757; author reply 758-9

Authors: Nair VS

PMID: 20181979 [PubMed - in process]

Traffic control for BRCA1.

N Engl J Med. 2010 Feb 25;362(8):755-6

Authors: Foulkes WD

PMID: 20181978 [PubMed - in process]

Revascularization for renal-artery stenosis.

N Engl J Med. 2010 Feb 25;362(8):762; author reply 763-4

Authors: Staub D, Uthoff H, Jaeger KA

PMID: 20181982 [PubMed - in process]