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1.  Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in Myelofibrosis 
The New England journal of medicine  2010;363(12):1117-1127.
Background
Myelofibrosis is a Philadelphia chromosome–negative myeloproliferative neoplasm associated with cytopenias, splenomegaly, poor quality of life, and shortened survival. About half of patients with myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene (JAK2 V617F) that contributes to the pathophysiology of the disease. INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor.
Methods
We conducted a phase 1–2 trial of INCB018424 in patients with JAK2 V617F–positive or JAK2 V617F–negative primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis.
Results
A total of 153 patients received INCB018424 for a median duration of more than 14.7 months. The initial dose-escalation phase established 25 mg twice daily or 100 mg once daily as maximum tolerated doses, on the basis of reversible thrombocytopenia. A dose-dependent suppression of phosphorylated signal transducer and activator of transcription 3 (STAT3), a marker of JAK signaling, was demonstrated in patients with wild-type JAK2 and in patients with the JAK2 V617F mutation. We studied additional doses and established that a 15-mg twice-daily starting dose, followed by individualized dose titration, was the most effective and safest dosing regimen. At this dose, 17 of 33 patients (52%) had a rapid objective response (≥50% reduction of splenomegaly) lasting for 12 months or more, and this therapy was associated with grade 3 or grade 4 adverse events (mainly myelosuppression) in less than 10% of patients. Patients with debilitating symptoms, including weight loss, fatigue, night sweats, and pruritus, had rapid improvement. Clinical benefits were associated with a marked diminution of levels of circulating inflammatory cytokines that are commonly elevated in myelofibrosis.
Conclusions
INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed.
doi:10.1056/NEJMoa1002028
PMCID: PMC5187954  PMID: 20843246
2.  Renal Transplantation between HIV-Positive Donors and Recipients 
The New England journal of medicine  2010;362(24):2336-2337.
doi:10.1056/NEJMc0900837
PMCID: PMC5094174  PMID: 20554994
3.  Lung Function in Rescue Workers at the World Trade Center after 7 Years 
The New England journal of medicine  2010;362(14):1263-1272.
Background
The terrorist attacks on the World Trade Center on September 11, 2001, exposed thousands of Fire Department of New York City (FDNY) rescue workers to dust, leading to substantial declines in lung function in the first year. We sought to determine the longer-term effects of exposure.
Methods
Using linear mixed models, we analyzed the forced expiratory volume in 1 second (FEV1) of both active and retired FDNY rescue workers on the basis of spirometry routinely performed at intervals of 12 to 18 months from March 12, 2000, to September 11, 2008.
Results
Of the 13,954 FDNY workers who were present at the World Trade Center between September 11, 2001, and September 24, 2001, a total of 12,781 (91.6%) participated in this study, contributing 61,746 quality-screened spirometric measurements. The median follow-up was 6.1 years for firefighters and 6.4 years for emergency-medical-services (EMS) workers. In the first year, the mean FEV1 decreased significantly for all workers, more for firefighters who had never smoked (a reduction of 439 ml; 95% confidence interval [CI], 408 to 471) than for EMS workers who had never smoked (a reduction of 267 ml; 95% CI, 263 to 271) (P<0.001 for both comparisons). There was little or no recovery in FEV1 during the subsequent 6 years, with a mean annualized reduction in FEV1 of 25 ml per year for firefighters and 40 ml per year for EMS workers. The proportion of workers who had never smoked and who had an FEV1 below the lower limit of the normal range increased during the first year, from 3% to 18% for firefighters and from 12% to 22% for EMS workers, stabilizing at about 13% for firefighters and 22% for EMS workers during the subsequent 6 years.
Conclusions
Exposure to World Trade Center dust led to large declines in FEV1 for FDNY rescue workers during the first year. Overall, these declines were persistent, without recovery over the next 6 years, leaving a substantial proportion of workers with abnormal lung function.
doi:10.1056/NEJMoa0910087
PMCID: PMC4940972  PMID: 20375403
4.  Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema 
The New England journal of medicine  2010;363(6):532-541.
BACKGROUND
Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.
METHODS
In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.
RESULTS
A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P = 0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.
CONCLUSIONS
In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
doi:10.1056/NEJMoa0906393
PMCID: PMC4662377  PMID: 20818888
5.  AIDS in America — Forgotten but Not Gone 
The New England journal of medicine  2010;362(11):967-970.
doi:10.1056/NEJMp1000069
PMCID: PMC4568988  PMID: 20147707
6.  A Large-Scale, Consortium-Based Genomewide Association Study of Asthma 
The New England journal of medicine  2010;363(13):1211-1221.
BACKGROUND
Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease.
METHODS
We carried out a genomewide association study by genotyping 10,365 persons with physician-diagnosed asthma and 16,110 unaffected persons, all of whom were matched for ancestry. We used random-effects pooled analysis to test for association in the overall study population and in subgroups of subjects with childhood-onset asthma (defined as asthma developing before 16 years of age), later-onset asthma, severe asthma, and occupational asthma.
RESULTS
We observed associations of genomewide significance between asthma and the following single-nucleotide polymorphisms: rs3771166 on chromosome 2, implicating IL1RL1/IL18R1 (P =3×10−9); rs9273349 on chromosome 6, implicating HLA-DQ (P = 7×10−14); rs1342326 on chromosome 9, flanking IL33 (P = 9×10−10); rs744910 on chromosome 15 in SMAD3 (P = 4×10−9); and rs2284033 on chromosome 22 in IL2RB (P = 1.1×10−8). Association with the ORMDL3/GSDMB locus on chromosome 17q21 was specific to childhood-onset disease (rs2305480, P = 6×10−23). Only HLA-DR showed a significant genomewide association with the total serum IgE concentration, and loci strongly associated with IgE levels were not associated with asthma.
CONCLUSIONS
Asthma is genetically heterogeneous. A few common alleles are associated with disease risk at all ages. Implicated genes suggest a role for communication of epithelial damage to the adaptive immune system and activation of airway inflammation. Variants at the ORMDL3/GSDMB locus are associated only with childhood-onset disease. Elevation of total serum IgE levels has a minor role in the development of asthma. (Funded by the European Commission and others.)
doi:10.1056/NEJMoa0906312
PMCID: PMC4260321  PMID: 20860503
7.  Dietary Intervention in Infancy and Later Signs of Beta-Cell Autoimmunity 
The New England journal of medicine  2010;363(20):1900-1908.
BACKGROUND
Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and type 1 diabetes in children with genetic susceptibility. We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children.
METHODS
In this double-blind, randomized trial, we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional, cow’s-milk–based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. Autoantibodies to insulin, glutamic acid decarboxylase (GAD), the insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 were analyzed with the use of radiobinding assays, and islet-cell antibodies were analyzed with the use of immunofluorescence, during a median observation period of 10 years (mean, 7.5). The children were monitored for incident type 1 diabetes until they were 10 years of age.
RESULTS
The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group, as compared with the control group, was 0.54 (95% confidence interval [CI], 0.29 to 0.95), and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 (95% CI, 0.28 to 0.91). The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 (95% CI, 0.21 to 1.17), and the adjusted hazard ratio was 0.47 (95% CI, 0.19 to 1.07). The rate of reported adverse events was similar in the two groups.
CONCLUSIONS
Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity — markers that may reflect an autoimmune process leading to type 1 diabetes. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00570102.)
doi:10.1056/NEJMoa1004809
PMCID: PMC4242902  PMID: 21067382
8.  Molecular Architecture of the Goodpasture Autoantigen in Anti-GBM Nephritis 
The New England journal of medicine  2010;363(4):343-354.
BACKGROUND
In Goodpasture’s disease, circulating autoantibodies bind to the noncollagenous-1 (NC1) domain of type IV collagen in the glomerular basement membrane (GBM). The specificity and molecular architecture of epitopes of tissue-bound autoantibodies are unknown. Alport’s post-transplantation nephritis, which is mediated by alloantibodies against the GBM, occurs after kidney transplantation in some patients with Alport’s syndrome. We compared the conformations of the antibody epitopes in Goodpasture’s disease and Alport’s post-transplantation nephritis with the intention of finding clues to the pathogenesis of anti-GBM glomerulonephritis.
METHODS
We used an enzyme-linked immunosorbent assay to determine the specificity of circulating autoantibodies and kidney-bound antibodies to NC1 domains. Circulating antibodies were analyzed in 57 patients with Goodpasture’s disease, and kidney-bound antibodies were analyzed in 14 patients with Goodpasture’s disease and 2 patients with Alport’s post-transplantation nephritis. The molecular architecture of key epitope regions was deduced with the use of chimeric molecules and a three-dimensional model of the α345NC1 hexamer.
RESULTS
In patients with Goodpasture’s disease, both autoantibodies to the α3NC1 monomer and antibodies to the α5NC1 monomer (and fewer to the α4NC1 monomer) were bound in the kidneys and lungs, indicating roles for the α3NC1 and α5NC1 monomers as autoantigens. High antibody titers at diagnosis of anti-GBM disease were associated with ultimate loss of renal function. The antibodies bound to distinct epitopes encompassing region EA in the α5NC1 monomer and regions EA and EB in the α3NC1 monomer, but they did not bind to the native cross-linked α345NC1 hexamer. In contrast, in patients with Alport’s post-transplantation nephritis, alloantibodies bound to the EA region of the α5NC1 subunit in the intact hexamer, and binding decreased on dissociation.
CONCLUSIONS
The development of Goodpasture’s disease may be considered an autoimmune “conformeropathy” that involves perturbation of the quaternary structure of the α345NC1 hexamer, inducing a pathogenic conformational change in the α3NC1 and α5NC1 subunits, which in turn elicits an autoimmune response. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)
doi:10.1056/NEJMoa0910500
PMCID: PMC4144421  PMID: 20660402
9.  Immunotherapy for Sepsis: a new approach against an ancient foe 
doi:10.1056/NEJMcibr1004371
PMCID: PMC4136660  PMID: 20592301
10.  Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus 
The New England journal of medicine  2010;362(17):1575-1585.
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.)
doi:10.1056/NEJMoa1001286
PMCID: PMC4123215  PMID: 20228401
11.  Genetics, Epigenetics and Leukemia 
The New England journal of medicine  2010;363(25):2460-2461.
doi:10.1056/NEJMe1012071
PMCID: PMC4117480  PMID: 21067376
12.  Vaccine-Acquired Rotavirus in Infants with Severe Combined Immunodeficiency 
The New England journal of medicine  2010;362(4):314-319.
SUMMARY
Live pentavalent human–bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients.
doi:10.1056/NEJMoa0904485
PMCID: PMC4103739  PMID: 20107217
13.  Bitter Pills 
The New England journal of medicine  2010;363(19):1847-1851.
doi:10.1056/NEJMcps0904937
PMCID: PMC4098700  PMID: 21047229
14.  Comparative Epidemiology of Pandemic and Seasonal Influenza A in Households 
The New England journal of medicine  2010;362(23):2175-2184.
BACKGROUND
There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings.
METHODS
We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses.
RESULTS
Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness.
CONCLUSIONS
Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.
doi:10.1056/NEJMoa0911530
PMCID: PMC4070281  PMID: 20558368
15.  Airway Mucus Function and Dysfunction 
The New England journal of medicine  2010;363(23):2233-2247.
doi:10.1056/NEJMra0910061
PMCID: PMC4048736  PMID: 21121836
16.  Immune Evasion by Chimeric Trachea 
The New England journal of medicine  2010;362(2):172-174.
doi:10.1056/NEJMe0908366
PMCID: PMC4045014  PMID: 20071709
17.  Whole-Genome Sequencing in a Patient with Charcot–Marie–Tooth Neuropathy 
The New England journal of medicine  2010;362(13):1181-1191.
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.
doi:10.1056/NEJMoa0908094
PMCID: PMC4036802  PMID: 20220177
18.  Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes 
The New England journal of medicine  2010;363(3):233-244.
BACKGROUND
We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy.
METHODS
In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy.
RESULTS
At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P = 0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P = 0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29).
CONCLUSIONS
Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)
doi:10.1056/NEJMoa1001288
PMCID: PMC4026164  PMID: 20587587
19.  The Emerging Importance of Patient Amenities in Hospital Care 
The New England journal of medicine  2010;363(23):2185-2187.
doi:10.1056/NEJMp1009501
PMCID: PMC4023463  PMID: 21121830
21.  Indoor Tanning — Science, Behavior, and Policy 
The New England journal of medicine  2010;363(10):901-903.
doi:10.1056/NEJMp1005999
PMCID: PMC3951814  PMID: 20818900
22.  Low Diagnostic Yield of Elective Coronary Angiography 
The New England journal of medicine  2010;362(10):886-895.
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.
doi:10.1056/NEJMoa0907272
PMCID: PMC3920593  PMID: 20220183
23.  Graves’ Ophthalmopathy 
The New England journal of medicine  2010;362(8):726-738.
Graves’ ophthalmopathy, also called Graves’ orbitopathy, is a potentially sight-threatening ocular disease that has puzzled physicians and scientists for nearly two centuries.1–3 Generally occurring in patients with hyperthyroidism or a history of hyperthyroidism due to Graves’ disease, Graves’ ophthalmopathy is also known as thyroid-associated ophthalmopathy or thyroid eye disease, because it sometimes occurs in patients with euthyroid or hypothyroid chronic autoimmune thyroiditis. The condition has an annual adjusted incidence rate of 16 women and 3 men per 100,000 population.4
This review explores the perplexing relationship between Graves’ ophthalmopathy, hyperthyroidism, and thyroid dermopathy, the associated skin condition. I examine clinical features, histologic findings, and laboratory studies, with an emphasis on mechanisms that could be targeted in the development of new treatments for this debilitating disease.
doi:10.1056/NEJMra0905750
PMCID: PMC3902010  PMID: 20181974
24.  Placebo-Controlled Trials in Osteoporosis — Proceeding with Caution 
The New England journal of medicine  2010;363(14):1365-e22.
This article presents one viewpoint on the issues surrounding placebo-controlled trials in osteoporosis. The other Sounding Board article in this issue presents an opposing view. At NEJM.org, in a related interactive feature, the authors of each article give their Point of View about the other article. At NEJM.org, readers can participate in forming community opinion by choosing one of the viewpoints and, if they like, providing their reasons.
doi:10.1056/NEJMsb1002227
PMCID: PMC3901575  PMID: 20879887

Results 1-25 (126)