PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (118)
 

Clipboard (0)
None
Journals
Year of Publication
2.  The Many Causes of Severe Congenital Neutropenia 
doi:10.1056/NEJMp0806821
PMCID: PMC4162527  PMID: 19118300
3.  Lack of Association between Folate-Receptor Autoantibodies and Neural-Tube Defects 
The New England journal of medicine  2009;361(2):152-160.
BACKGROUND
A previous report described the presence of autoantibodies against folate receptors in 75% of serum samples from women with a history of pregnancy complicated by a neural-tube defect, as compared with 10% of controls. We sought to confirm this finding in an Irish population, which traditionally has had a high prevalence of neuraltube defects.
METHODS
We performed two studies. Study 1 consisted of analysis of stored frozen blood samples collected from 1993 through 1994 from 103 mothers with a history of pregnancy complicated by a neural-tube defect (case mothers), 103 mothers with a history of pregnancy but no complication by a neural-tube defect (matched with regard to number of pregnancies and sampling dates), 58 women who had never been pregnant, and 36 men. Study 2, conducted to confirm that the storage of samples did not influence the folate-receptor autoantibodies, included fresh samples from 37 case mothers, 22 control mothers, 10 women who had never been pregnant, and 9 men. All samples were assayed for blocking and binding autoantibodies against folate receptors.
RESULTS
In Study 1, blocking autoantibodies were found in 17% of case mothers, as compared with 13% of control mothers (odds ratio, 1.54; 95% confidence interval [CI], 0.70 to 3.39), and binding autoantibodies in 29%, as compared with 32%, respectively (odds ratio, 0.82; 95% CI, 0.44 to 1.50). Study 2 showed similar results, indicating that sample degradation was unlikely.
CONCLUSIONS
The presence and titer of maternal folate-receptor autoantibodies were not significantly associated with a neural-tube defect–affected pregnancy in this Irish population.
doi:10.1056/NEJMoa0803783
PMCID: PMC4149290  PMID: 19587340
6.  Cardiomyocyte Renewal 
doi:10.1056/NEJMcibr0903347
PMCID: PMC4111249  PMID: 19571289
7.  Long-Term Ozone Exposure and Mortality 
The New England journal of medicine  2009;360(11):1085-1095.
BACKGROUND
Although many studies have linked elevations in tropospheric ozone to adverse health outcomes, the effect of long-term exposure to ozone on air pollution–related mortality remains uncertain. We examined the potential contribution of exposure to ozone to the risk of death from cardiopulmonary causes and specifically to death from respiratory causes.
METHODS
Data from the study cohort of the American Cancer Society Cancer Prevention Study II were correlated with air-pollution data from 96 metropolitan statistical areas in the United States. Data were analyzed from 448,850 subjects, with 118,777 deaths in an 18-year follow-up period. Data on daily maximum ozone concentrations were obtained from April 1 to September 30 for the years 1977 through 2000. Data on concentrations of fine particulate matter (particles that are ≤2.5 μm in aerodynamic diameter [PM2.5]) were obtained for the years 1999 and 2000. Associations between ozone concentrations and the risk of death were evaluated with the use of standard and multilevel Cox regression models.
RESULTS
In single-pollutant models, increased concentrations of either PM2.5 or ozone were significantly associated with an increased risk of death from cardiopulmonary causes. In two-pollutant models, PM2.5 was associated with the risk of death from cardiovascular causes, whereas ozone was associated with the risk of death from respiratory causes. The estimated relative risk of death from respiratory causes that was associated with an increment in ozone concentration of 10 ppb was 1.040 (95% confidence interval, 1.010 to 1.067). The association of ozone with the risk of death from respiratory causes was insensitive to adjustment for confounders and to the type of statistical model used.
CONCLUSIONS
In this large study, we were not able to detect an effect of ozone on the risk of death from cardiovascular causes when the concentration of PM2.5 was taken into account. We did, however, demonstrate a significant increase in the risk of death from respiratory causes in association with an increase in ozone concentration.
doi:10.1056/NEJMoa0803894
PMCID: PMC4105969  PMID: 19279340
8.  Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma 
The New England journal of medicine  2009;360(10):973-984.
BACKGROUND
Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.
METHODS
We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV1) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.
RESULTS
Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P = 0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P = 0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P = 0.002). There were no significant differences between the groups with respect to symptoms, FEV1 after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.
CONCLUSIONS
Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)
doi:10.1056/NEJMoa0808991
PMCID: PMC3992367  PMID: 19264686
9.  Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women 
The New England journal of medicine  2009;360(6):573-587.
BACKGROUND
Following the release of the 2002 report of the Women’s Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.
METHODS
We analyzed the results of the WHI randomized clinical trial — in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxy-progesterone acetate daily and another group received placebo — and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use.
RESULTS
In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.
CONCLUSIONS
The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.
doi:10.1056/NEJMoa0807684
PMCID: PMC3963492  PMID: 19196674
10.  Effect of Dipyridamole plus Aspirin on Hemodialysis Graft Patency 
The New England journal of medicine  2009;360(21):2191-2201.
BACKGROUND
Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity.
METHODS
We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates.
RESULTS
At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole–aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups.
CONCLUSIONS
Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)
doi:10.1056/NEJMoa0805840
PMCID: PMC3929400  PMID: 19458364
11.  Increasing Options for the Treatment of Osteoporosis 
The New England journal of medicine  2009;361(8):818-820.
doi:10.1056/NEJMe0905480
PMCID: PMC3901579  PMID: 19671654
12.  Norovirus Gastroenteritis 
The New England journal of medicine  2009;361(18):10.1056/NEJMra0804575.
doi:10.1056/NEJMra0804575
PMCID: PMC3880795  PMID: 19864676
13.  Household Transmission of 2009 Pandemic Influenza A (H1N1) Virus in the United States 
The New England journal of medicine  2009;361(27):10.1056/NEJMoa0905498.
BACKGROUND
As of June 11, 2009, a total of 17,855 probable or confirmed cases of 2009 pandemic influenza A (H1N1) had been reported in the United States. Risk factors for transmission remain largely uncharacterized. We characterize the risk factors and describe the transmission of the virus within households.
METHODS
Probable and confirmed cases of infection with the 2009 H1N1 virus in the United States were reported to the Centers for Disease Control and Prevention with the use of a standardized case form. We investigated transmission of infection in 216 households — including 216 index patients and their 600 household contacts — in which the index patient was the first case patient and complete information on symptoms and age was available for all household members.
RESULTS
An acute respiratory illness developed in 78 of 600 household contacts (13%). In 156 households (72% of the 216 households), an acute respiratory illness developed in none of the household contacts; in 46 households (21%), illness developed in one contact; and in 14 households (6%), illness developed in more than one contact. The proportion of household contacts in whom acute respiratory illness developed decreased with the size of the household, from 28% in two-member households to 9% in six-member households. Household contacts 18 years of age or younger were twice as susceptible as those 19 to 50 years of age (relative susceptibility, 1.96; Bayesian 95% credible interval, 1.05 to 3.78; P = 0.005), and household contacts older than 50 years of age were less susceptible than those who were 19 to 50 years of age (relative susceptibility, 0.17; 95% credible interval, 0.02 to 0.92; P = 0.03). Infectivity did not vary with age. The mean time between the onset of symptoms in a case patient and the onset of symptoms in the household contacts infected by that patient was 2.6 days (95% credible interval, 2.2 to 3.5).
CONCLUSIONS
The transmissibility of the 2009 H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms in a case patient.
doi:10.1056/NEJMoa0905498
PMCID: PMC3840270  PMID: 20042753
14.  Understanding Abdominal Aortic Aneurysm 
The New England journal of medicine  2009;361(11):1114-1116.
doi:10.1056/NEJMcibr0905244
PMCID: PMC3791612  PMID: 19741234
17.  The Microcytic Red Cell and the Anemia of Inflammation 
The New England journal of medicine  2009;361(19):1904-1906.
doi:10.1056/NEJMcibr0906391
PMCID: PMC3741048  PMID: 19890136
18.  Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures in the United States 
The New England journal of medicine  2009;361(9):849-857.
Background
Growing use of imaging procedures in the United States has raised concerns about exposure to low-dose ionizing radiation in the general population.
Methods
We identified 952,420 non-elderly adults in 5 healthcare markets across the United States between July 1, 2005 and December 31, 2007. Utilization data were used to determine cumulative effective doses of radiation from imaging procedures in millisieverts (mSv) and to calculate population-based rates of “moderate” (>3 to 20 mSv per year), “high” (>20 to 50 mSv per year) and “very-high” (>50 mSv per year) doses.
Results
During the study period, 655,613 (68.8%) individuals underwent at least 1 imaging procedure associated with radiation exposure. The mean effective dose from imaging procedures was 2.4 mSv per person per year (std dev, 6.0 mSv); however, a wide distribution was noted with a median effective dose of 0.1 mSv per person per year (interquartile range, 0.0 to 1.7). Overall, the annual rate for moderate effective doses in the study population was 193.8 per 1000 enrollees, while high and very-high doses occurred at annual rates of 18.6 per 1000 enrollees and 1.9 per 1000 enrollees, respectively. In general, effective doses of radiation from imaging procedures increased with advancing age and were higher in women. Computed tomography and nuclear medicine scans accounted for 75.4% of the total effective dose and 81.8% occurred in non-hospitalized settings.
Conclusions
Imaging procedures are an important source of ionizing radiation in the United States and can lead to high radiation doses in patients.
doi:10.1056/NEJMoa0901249
PMCID: PMC3707303  PMID: 19710483
19.  Memory and the NMDA Receptors 
The New England journal of medicine  2009;361(3):302-303.
doi:10.1056/NEJMcibr0902052
PMCID: PMC3703758  PMID: 19605837
20.  Primary Open-Angle Glaucoma 
The New England journal of medicine  2009;360(11):1113-1124.
doi:10.1056/NEJMra0804630
PMCID: PMC3700399  PMID: 19279343
23.  Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease 
The New England journal of medicine  2009;361(24):2309-2317.
BACKGROUND
Myeloablative allogeneic hematopoietic stem-cell transplantation is curative in children with sickle cell disease, but in adults the procedure is unduly toxic. Graft rejection and graft-versus-host disease (GVHD) are additional barriers to its success. We performed nonmyeloablative stem-cell transplantation in adults with sickle cell disease.
METHODS
Ten adults (age range, 16 to 45 years) with severe sickle cell disease underwent nonmyeloablative transplantation with CD34+ peripheral-blood stem cells, mobilized by granulocyte colony-stimulating factor (G-CSF), which were obtained from HLA-matched siblings. The patients received 300 cGy of total-body irradiation plus alemtuzumab before transplantation, and sirolimus was administered afterward.
RESULTS
All 10 patients were alive at a median follow-up of 30 months after transplantation (range, 15 to 54). Nine patients had long-term, stable donor lymphohematopoietic engraftment at levels that sufficed to reverse the sickle cell disease phenotype. Mean (±SE) donor–recipient chimerism for T cells (CD3+) and myeloid cells (CD14+15+) was 53.3±8.6% and 83.3±10.3%, respectively, in the nine patients whose grafts were successful. Hemoglobin values before transplantation and at the last follow-up assessment were 9.0±0.3 and 12.6±0.5 g per deciliter, respectively. Serious adverse events included the narcotic-withdrawal syndrome and sirolimus-associated pneumonitis and arthralgia. Neither acute nor chronic GVHD developed in any patient.
CONCLUSIONS
A protocol for nonmyeloablative allogeneic hematopoietic stem-cell transplantation that includes total-body irradiation and treatment with alemtuzumab and sirolimus can achieve stable, mixed donor–recipient chimerism and reverse the sickle cell phenotype.
doi:10.1056/NEJMoa0904971
PMCID: PMC3627532  PMID: 20007560
24.  Rates of Serious Infection after Changes in Regimens for Medical Abortion 
The New England journal of medicine  2009;361(2):145-151.
BACKGROUND
From 2001 through March 2006, Planned Parenthood health centers throughout the United States provided medical abortion (abortion by means of medication) principally by a regimen of oral mifepristone followed 24 to 48 hours later by vaginal misoprostol. In response to concern about serious infections, in early 2006 Planned Parenthood changed the route of misoprostol administration from vaginal to buccal and required either routine provision of antibiotics or universal screening and treatment for chlamydia; in July 2007, Planned Parenthood began requiring routine treatment with antibiotics for all medical abortions.
METHODS
We performed a retrospective analysis assessing the rates of serious infection after medical abortion during a time when misoprostol was administered vaginally (through March 2006), as compared with rates after a change to buccal administration of misoprostol and after initiation of additional infection-reduction measures.
RESULTS
Rates of serious infection dropped significantly after the joint change to buccal misoprostol from vaginal misoprostol and to either testing for sexually transmitted infection or routine provision of antibiotics as part of the medical abortion regimen. The rate declined 73%, from 0.93 per 1000 abortions to 0.25 per 1000 (absolute reduction, 0.67 per 1000; 95% confidence interval [CI], 0.44 to 0.94; P<0.001). The subsequent change to routine provision of antibiotics led to a further significant reduction in the rate of serious infection — a 76% decline, from 0.25 per 1000 abortions to 0.06 per 1000 (absolute reduction, 0.19 per 1000; 95% CI, 0.02 to 0.34; P = 0.03).
CONCLUSIONS
The rate of serious infection after medical abortion declined by 93% after a change from vaginal to buccal administration of misoprostol combined with routine administration of antibiotics.
doi:10.1056/NEJMoa0809146
PMCID: PMC3568698  PMID: 19587339
25.  Long-Term Consequences of Kidney Donation 
The New England journal of medicine  2009;360(5):459-469.
BACKGROUND
The long-term renal consequences of kidney donation by a living donor are attracting increased appropriate interest. The overall evidence suggests that living kidney donors have survival similar to that of nondonors and that their risk of end-stage renal disease (ESRD) is not increased. Previous studies have included relatively small numbers of donors and a brief follow-up period.
METHODS
We ascertained the vital status and lifetime risk of ESRD in 3698 kidney donors who donated kidneys during the period from 1963 through 2007; from 2003 through 2007, we also measured the glomerular filtration rate (GFR) and urinary albumin excretion and assessed the prevalence of hypertension, general health status, and quality of life in 255 donors.
RESULTS
The survival of kidney donors was similar to that of controls who were matched for age, sex, and race or ethnic group. ESRD developed in 11 donors, a rate of 180 cases per million persons per year, as compared with a rate of 268 per million per year in the general population. At a mean (±SD) of 12.2±9.2 years after donation, 85.5% of the subgroup of 255 donors had a GFR of 60 ml per minute per 1.73 m2 of body-surface area or higher, 32.1% had hypertension, and 12.7% had albuminuria. Older age and higher body-mass index, but not a longer time since donation, were associated with both a GFR that was lower than 60 ml per minute per 1.73 m2 and hypertension. A longer time since donation, however, was independently associated with albuminuria. Most donors had quality-of-life scores that were better than population norms, and the prevalence of coexisting conditions was similar to that among controls from the National Health and Nutrition Examination Survey (NHANES) who were matched for age, sex, race or ethnic group, and body-mass index.
CONCLUSIONS
Survival and the risk of ESRD in carefully screened kidney donors appear to be similar to those in the general population. Most donors who were studied had a preserved GFR, normal albumin excretion, and an excellent quality of life.
doi:10.1056/NEJMoa0804883
PMCID: PMC3559132  PMID: 19179315

Results 1-25 (118)