Blechacz, Boris; Gajic, Ognjen
doi: 10.1056/NEJMicm074057pmid: 18550872
This 89-year-old woman was admitted with hypercapnic respiratory failure. She had a long history of osteoporosis and multiple vertebral compression fractures.
Krumholz, Harlan M.; Lee, Thomas H.
doi: 10.1056/NEJMp0803740pmid: 18539915
The conventional wisdom for guidelines and performance measures has been that the clinician's key focus ought to be on reducing risk factors below specific levels. Drs. Harlan Krumholz and Thomas Lee argue that this approach neglects the importance of which specific strategies are used to modify these factors.
doi: 10.1056/NEJMp0803650pmid: 18550873
The quest for a fully immunogenic vaccine against influenza H5N1 viruses has gone on for more than 10 years. Dr. Peter Wright writes that with tissue-culture–grown vaccine, the production schedule could be altered to permit incorporation of late-emerging threats.
doi: 10.1056/NEJMoa0802743pmid: 18539917
BackgroundEpidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.MethodsIn this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up.ResultsAt 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001).ConclusionsAs compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)
doi: 10.1056/NEJMoa0802987pmid: 18539916
BackgroundIn patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.MethodsWe randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.ResultsAfter a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).ConclusionsA strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)
Ehrlich, Hartmut J.; Müller, Markus; Oh, Helen M.L.; Tambyah, Paul A.; Joukhadar, Christian; Montomoli, Emanuele; Fisher, Dale; Berezuk, Greg; Fritsch, Sandor; Löw-Baselli, Alexandra; Vartian, Nina; Bobrovsky, Roman; Pavlova, Borislava G.; Pöllabauer, Eva Maria; Kistner, Otfried;
Maris, John M.; Mosse, Yael P.; Bradfield, Jonathan P.; Hou, Cuiping; Monni, Stefano; Scott, Richard H.; Asgharzadeh, Shahab; Attiyeh, Edward F.; Diskin, Sharon J.; Laudenslager, Marci; Winter, Cynthia; Cole, Kristina A.; Glessner, Joseph T.; Kim, Cecilia; Frackelton, Edward C.;
doi: 10.1056/NEJMcp0801880pmid: 18550875
A 23-year-old woman has palpitations. Over the past 6 months, she has had a 10-lb (4.5-kg) weight loss. Her pulse is 119 beats per minute, and blood pressure is 137/80 mm Hg. Her thyroid gland is diffusely enlarged. She has eyelid lag but no proptosis. The level of thyrotropin is 0.02 μU per ml (normal range, 0.35 to 4.50), and free thyroxine is 4.10 ng per deciliter (normal range, 0.89 to 1.76). How should she be further evaluated and treated?
Jager, Rama D.; Mieler, William F.; Miller, Joan W.
doi: 10.1056/NEJMra0801537pmid: 18550876
Age-related macular degeneration is the leading cause of irreversible blindness in people 50 years of age or older in the developed world. This article reviews the clinical and histopathological features of age-related macular degeneration and its genetics and epidemiology and discusses current management options and research advances.
Showing 1 to 10 of 26 Articles
doi: 10.1056/NEJMoa073121pmid: 18550874
BackgroundWidespread infections of avian species with avian influenza H5N1 virus and its limited spread to humans suggest that the virus has the potential to cause a human influenza pandemic. An urgent need exists for an H5N1 vaccine that is effective against divergent strains of H5N1 virus.MethodsIn a randomized, dose-escalation, phase 1 and 2 study involving six subgroups, we investigated the safety of an H5N1 whole-virus vaccine produced on Vero cell cultures and determined its ability to induce antibodies capable of neutralizing various H5N1 strains. In two visits 21 days apart, 275 volunteers between the ages of 18 and 45 years received two doses of vaccine that each contained 3.75 μg, 7.5 μg, 15 μg, or 30 μg of hemagglutinin antigen with alum adjuvant or 7.5 μg or 15 μg of hemagglutinin antigen without adjuvant. Serologic analysis was performed at baseline and on days 21 and 42.ResultsThe vaccine induced a neutralizing immune response not only against the clade 1 (A/Vietnam/1203/2004) virus strain but also against the clade 2 and 3 strains. The use of adjuvants did not improve the antibody response. Maximum responses to the vaccine strain were obtained with formulations containing 7.5 μg and 15 μg of hemagglutinin antigen without adjuvant. Mild pain at the injection site (in 9 to 27% of subjects) and headache (in 6 to 31% of subjects) were the most common adverse events identified for all vaccine formulations.ConclusionsA two-dose vaccine regimen of either 7.5 μg or 15 μg of hemagglutinin antigen without adjuvant induced neutralizing antibodies against diverse H5N1 virus strains in a high percentage of subjects, suggesting that this may be a useful H5N1 vaccine. (ClinicalTrials.gov number, NCT00349141.)
doi: 10.1056/NEJMoa0708698pmid: 18463370
BackgroundNeuroblastoma is a malignant condition of the developing sympathetic nervous system that most commonly affects young children and is often lethal. Its cause is not known.MethodsWe performed a genomewide association study by first genotyping blood DNA samples from 1032 patients with neuroblastoma and 2043 control subjects of European descent using the Illumina HumanHap550 BeadChip. Samples from three independent groups of patients with neuroblastoma (a total of 720 patients) and 2128 control subjects were then genotyped to replicate significant associations.ResultsWe observed a significant association between neuroblastoma and the common minor alleles of three consecutive single-nucleotide polymorphisms (SNPs) at chromosome band 6p22 and containing the predicted genes FLJ22536 and FLJ44180 (P=1.71×10–9 to 7.01×10–10; allelic odds ratio, 1.39 to 1.40). Homozygosity for the at-risk G allele of the most significantly associated SNP, rs6939340, resulted in an increased likelihood of the development of neuroblastoma (odds ratio, 1.97; 95% confidence interval, 1.58 to 2.45). Subsequent genotyping of the three 6p22 SNPs in three independent case series confirmed our observation of an association (P=9.33×10–15 at rs6939340 for joint analysis). Patients with neuroblastoma who were homozygous for the risk alleles at 6p22 were more likely to have metastatic (stage 4) disease (P=0.02), amplification of the MYCN oncogene in the tumor cells (P=0.006), and disease relapse (P=0.01).ConclusionsA common genetic variation at chromosome band 6p22 is associated with susceptibility to neuroblastoma.