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New England Journal of Medicine The New England Journal of Medicine (NEJM) RSS feed -- current issue. NEJM (http://www.nejm.org) is a weekly general medical journal that publishes new medical research findings, review articles, and editorial opinion on a wide variety of topics of importance to biomedical science and clinical practice
New England Journal of Medicine On May 10, 2008, the Journal and the Massachusetts Medical Society brought together 13 panelists -- physicians, academics, and business, insurance, and political leaders -- for a seminar on U.S. ...
In the face of escalating costs, uneven quality of care, and the growth of the uninsured population, there is broad agreement that the U.S. health care system requires reform. However, ...
In the wake of Cyclone Nargis, which devastated the Myanmar delta in early May, and the seismic earthquake that shook China shortly thereafter, access to safe drinking water and proper ...
ORIGINAL ARTICLE: SLCO1B1 Variants and Statin-Induced Myopathy -- A Genomewide Study A genomewide screen of patients with myopathy who were taking high-dose simvastatin (80 mg per day) showed a strong association between myopathy and variants of SLCO1B1, which encodes an organic anion-transporting polypeptide. Approximately 60% of the cases of myopathy could be attributed to these variants. The association was replicated in an independent study. Genotyping SLCO1B1 variants may be helpful for tailoring the dosage of statins and safety monitoring.
ORIGINAL ARTICLE: Preeclampsia and the Risk of End-Stage Renal Disease By linking data from national medical registries in Norway, the investigators showed that women with a history of preeclampsia were at higher risk for subsequent end-stage renal disease than were women with a history of uncomplicated pregnancy. Women who had more preeclamptic pregnancies or who also had a low-birth-weight or preterm infant had higher relative risks for later end-stage renal disease. Preeclampsia is a marker for an increased risk of later end-stage renal disease, although the absolute risk in women who have had preeclampsia is still low.
ORIGINAL ARTICLE: Adalimumab with or without Methotrexate in Juvenile Rheumatoid Arthritis In this randomized, placebo-controlled trial of 133 children with polyarticular juvenile rheumatoid arthritis who had a response to a 16-week course of treatment with adalimumab, a monoclonal antibody to tumor necrosis factor, disease flares were less common when adalimumab was continued than when it was withdrawn. Fourteen patients had serious adverse events, including seven patients with serious infections.
SPECIAL ARTICLE: Health and Economic Implications of HPV Vaccination in the United States The authors conducted a cost-effectiveness analysis of human papillomavirus (HPV) vaccination in the United States and estimated that vaccinating 12-year-old girls would cost $43,600 per quality-adjusted life-year (QALY) gained, as compared with the current screening practice. If vaccine-induced immunity wanes after 10 years, HPV vaccination would be much less cost-effective (>$140,000 per QALY).
CLINICAL PRACTICE: Idiopathic Sudden Sensorineural Hearing Loss A healthy 58-year-old woman answers the telephone and realizes that her hearing is diminished on the left side. She notices aural fullness and loud tinnitus in the affected ear. Self-administered ear cleaning with the use of an over-the-counter kit does not relieve the symptoms. How should she be evaluated and treated?
A 23-year-old male Marine recruit passed out while bending over after a 2.4-km (1.5-mile) run. Chest radiography showed a mass in the anterior mediastinum (Panel A, arrow). His medical history ...
A 63-year-old woman presented with a 1-year history of vague pelvic and back pain. She had undergone laparoscopic surgery of the fallopian tubes 27 years earlier owing to infertility. Computed ...
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 26-2008 -- A 26-Year-Old Woman with Headache and Behavioral Changes A 26-year-old woman was admitted to this hospital because of headache, behavioral changes, abnormal movements, and inability to communicate. Seven weeks before admission, headaches developed, followed by somnolence, mood alteration, confusion, memory loss, incoherent speech, and involuntary movements. An evaluation for infection was negative. Imaging studies showed a normal brain and an ovarian mass consistent with a dermoid cyst. A diagnostic procedure was performed.
In this year's Shattuck Lecture, we break with long-standing precedent. After 117 Shattuck Lectures delivered since 1890, the lecture this year took the form of a seminar with 13 panelists ...
In the United States alone, it is estimated that adverse drug reactions affect nearly 2 million patients and kill about 100,000 people each year.1 Adverse drug reactions are often classified ...
Preeclampsia, a disorder of pregnancy characterized by elevated blood pressure and proteinuria, complicates approximately 5% of pregnancies.1 Although several risk factors for this condition are well recognized, including nulliparity, extremes ...
Despite great expectations and promising results of clinical trials, we still lack sufficient evidence of an effective vaccine against cervical cancer. Several strains of human papillomavirus (HPV) can cause cervical ...
To the Editor: In their review of the hepatopulmonary syndrome, Rodríguez-Roisin and Krowka (May 29 issue)1 provide a pathophysiological explanation ...
In 2007, spending on health care represented 16% of the U.S. economy -- a much greater percentage than that spent in nations with universal access to health care services -- ...
This masterly book is strong on diagnosis but, like much of medicine, rather light on evidence concerning the effectiveness of the treatment the authors propose to control drug prices. Drug ...
When the Willard Psychiatric Center, overlooking Seneca Lake in upstate New York, closed in 1995, a curator from the New York State Museum in Albany roamed the grounds, looking from ...
Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV Transmission . In the Abstract, the third sentence under Results (page 463) should have ended with "(hazard ...
Malignant Gliomas in Adults . The institution in Dr. Wen's address (page 492) should have read "Dana-Farber/Brigham and Women's Cancer Center." In Table 2 (page 503), the "Dendritic cell and ...
Treatment options for pulmonary arterial hypertension (PAH) have considerably improved in the past few years. Endothelin (ET)-receptor antagonism has been established as a first-line option for the majority of PAH patients. Endothelin-receptor antagonists (ETRAs) comprise sulfonamide and non-sulfonamide agents with different affinities for ET-receptor subtypes (ETA and ETB), and the focus of development has shifted from drugs with less selectivity to those with high selectivity. There is ongoing debate as to whether selective or non-selective ET-receptor antagonism is more beneficial in the treatment of PAH. This paper reviews the current evidence from experimental and clinical studies obtained from a thorough literature search focusing on the three marketed drugs bosentan, sitaxentan, and ambrisentan. A clinically meaningful difference among the three approved ETRAs with respect to their ET-receptor selectivity could not be demonstrated to date. Therefore, in clinical practice, other features are likely to be of greater relevance when considering treatment, such as the potential for serious drug–drug interactions, convenience of dosing schedule, or rates of limiting side effects. These characteristics bear more relation to the chemical or pharmacological properties of the drugs than to receptor selectivity itself.
Application of antibodies against cardiac troponin I (cTnI-Ab) can induce dilation and dysfunction of the heart in mice. Recently, we demonstrated that immunization with cTnI induces inflammation and fibrosis in myocardium of mice. Others have shown that auto-antibodies to cTnI are present in patients with acute coronary syndrome, but little is known about the clinical relevance of detected cTnI-Ab.
Methods and results
First, anti-cTnI and anti-cTnT antibody titres were measured in sera from 272 patients with dilated- (DCM) and 185 with ischaemic- (ICM) cardiomyopathy. Secondly, 108 patients with acute myocardial infarction (AMI) were included for a follow-up study. Heart characteristics were determined by magnetic resonance imaging 4 days and 6–9 months after AMI. Altogether in 7.0% of patients with DCM and in 9.2% with ICM, an anti-cTnI IgG antibody titre ≥1:160 was measured. In contrast, only in 1.7% of patients with DCM and in 0.5% with ICM, an anti-cTnT IgG antibody titre ≥1:160 was detected. Ten out of 108 patients included in the follow-up study were tested positive for cTnI-Ab with IgG Ab titres ≥1:160. TnI-Ab negative patients showed a significant increase in left ventricular ejection fraction (LVEF) and stroke volume 6–9 months after AMI. In contrast, there was no significant increase in LVEF and stroke volume in TnI-Ab positive patients.
Conclusion
We demonstrate for the first time that the prevalence of cTnI-Abs in patients with AMI has an impact on the improvement of the LVEF over a study period of 6–9 months.
To evaluate the impact of a combined treatment of angiotensin II type 1 (AT1)-receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition (statin) on the secretory phospholipase A2 type IIA (sPLA2-IIA) and oxidized low density lipoprotein (oxLDL) in patients with coronary artery disease (CAD).
Methods and results
Sixty patients with angiographically documented CAD and a history of arterial hypertension were randomized in a double-blinded fashion to pravastatin (PRAV, 40 mg/day, n = 30) or PRAV plus irbesartan (PRAV+IRB, 40 mg/day+300 mg/day, n = 30) and were treated for 3 months. Blood pressure (BP) and cholesterol fractions were determined at baseline and after 3 months. SPLA2 activity as primary endpoint, sPLA2-IIA protein, oxLDL levels, and high-sensitivity (hs)-C-reactive protein were measured by an enzyme-linked immunabsorbent assay. In both treatment groups, systolic BP levels and circulating HDL and LDL levels were reduced to the same extent. The combined treatment of PRAV+IRB significantly decreased sPLA2-IIA activity and sPLA2-IIA-protein concentration compared with PRAV treatment alone (P < 0.05). In addition, PRAV+IRB significantly reduced oxLDL levels compared with PRAV treatment alone (P < 0.05). This effect was independent of changes in LDL cholesterol levels.
Conclusion
These findings are consistent with the notion that the combined treatment of pravastatin with irbesartan reduced sPLA2-IIA-activity, sPLA2-IIA-protein concentration, and oxLDL in patients with CAD suggesting a novel anti-atherogenic effect by combining AT1-receptor blockade with statin treatment.
To compare whether novel inflammatory and haemostatic biomarkers are more predictive of well-characterized incident acute coronary syndrome (ACS) than stable angina (SA).
Methods and results
We used data from the PRIME Study, a prospective cohort of 9758 asymptomatic middle-aged men recruited in Northern Ireland and France between 1991 and 1993. A nested case–control study was established with the baseline plasma sample of 269 incident cases and 538 matched controls. Odds ratios (ORs) for SA and ACS were estimated by conditional logistic regression analysis. After 5 years of follow-up, 107 incident SA and 162 ACS cases were validated. After adjustment for traditional risk factors, higher circulating levels of hs-CRP, ICAM1, interleukin 6 and interleukin 18 were equally predictive of SA and ACS (all P-values of OR comparison >0.05). In contrast, elevated levels of fibrinogen, von Willebrand factor, and possibly higher level of D-dimers and lower level of tissue factor pathway inhibitor were associated with ACS only. The comparison of the ORs showed a statistically significant difference for von Willebrand factor only [OR4th vs. 1st quartile = 2.99 (1.49–6.02) for ACS vs. 0.80 (0.33–1.94) for SA; Pz test = 0.02].
Conclusion
This is the first population-based study suggesting that higher levels of circulating haemostatic markers and of von Willebrand factor, in particular, are significantly more predictive of incident ACS than SA.
The objective of this study was to assess the non-inferiority, in terms of anti-restenotic efficacy, of both biodegradable-polymer (BP) and polymer-free (PF) stents compared with permanent-polymer rapamycin-eluting (PP; Cypher) stent.
Methods and results
Patients with de novo coronary lesions in native vessels were randomly assigned to receive a BP stent, a PF stent or a PP stent. The primary endpoint was in-stent late lumen loss at follow-up angiogram.
A total of 605 patients were enrolled: 202 patients received BP stents, 202 were treated with PP stents, and 201 received PF stents. Repeat angiography was available for 492 patients (81.3%). Mean late lumen loss at 6–8-month angiographic follow-up was 0.17 ± 0.45 mm in the BP stent group, 0.23 ± 0.46 mm in the PP cohort, and 0.47 ± 0.56 mm in the PF stent group. The BP stent met pre-specified criteria for non-inferiority (P < 0.001), whereas the PF stent did not (P = 0.94). There were no differences in safety outcomes.
Conclusion
Both BP and PF stents have a 1-year safety profile similar to that of the PP stent. Whereas the PF stent provided an inferior efficacy, the BP stent is at least as effective as the PP stent in terms of anti-restenotic efficacy.
Cigarette smoking is a well-established risk factor for cardiovascular disease yet several studies have shown lower mortality after acute coronary syndromes in smokers compared with non-smokers, the so called ‘smoker’s paradox’. This study aimed to ascertain the relationship between smoking and clinical outcomes in patients hospitalized with heart failure (HF).
Methods and results
OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) collected data on 48 612 patients from 259 hospitals. Characteristics, treatments, and outcomes were compared for current/recent smokers vs. those without current/recent smoking, and multivariable regression analyses with adjustment for hospital clustering were performed. There were 7743 (15.9%) smokers, 39 126 (80.5%) non-smokers, and 1743 (3.6%) missing. Smokers were younger, had similar renal function, but lower ejection fraction. The risk of in-hospital mortality was less in smokers (2.3 vs. 3.9%, P < 0.001). After extensive covariate adjustment, smokers still had lower in-hospital mortality risk OR (odds ratio) 0.70, 95% CI (confidence interval) 0.56–0.88, P = 0.002. Post-discharge, smokers (n = 998) had similar mortality risk (6.7 vs. 8.4%, P = 0.29) compared with those without current/recent smoking.
Conclusion
Smokers hospitalized with HF had lower risk adjusted in-hospital mortality and similar early post-discharge mortality compared with non-smokers. The residual association of smoking and better prognosis, the ‘smoker’s paradox’, was not fully explained by measured covariates.
Following myocardial infarction (MI), both age and left ventricular (LV) remodelling are associated with an increased risk of adverse events. We tested the hypothesis that the increased incidence of heart failure following MI in elderly patients is associated with a greater propensity for LV remodelling.
Methods and results
We monitored 266 patients with anterior MI. Echocardiographic studies were performed at hospital discharge, at 3 months, and at 1 year following hospitalization for MI. A clinical follow-up examination was performed after 3 years. Left ventricular remodelling was documented by an increase in LV end-diastolic volume after 1 year. Left ventricular end-diastolic and end-systolic volumes did not differ with age for all time points studied. Left ventricular remodelling was observed in 31, 26, 34, and 34% of patients <48, 48–57, 58–71, and >71 years of age, respectively. The 3 year heart-failure hospitalization rates were 1.9, 1.5, 11.0, and 20.3% for patients <48, 48–57, 58–71, and >71 years of age, respectively. Hospitalization for heart failure was more frequent in older patients.
Conclusion
We found that age was a major determinant of subsequent re-hospitalization for heart failure. However, we found no significant association between age and the LV remodelling process.
We sought to evaluate the relation between long-term functional outcome after revascularization in patients with chronic ischaemic left ventricular (LV) dysfunction and baseline extent of myocardial fibrosis.
Methods and results
Thirty-five patients underwent cine and delayed contrast-enhanced cardiovascular magnetic resonance (deCMR) for the quantitative assessment of regional and global LV functions and segmental extent of hyperenhancement (SEH). Function was assessed 1 month before and 3, 6, and 24 ± 12 months after revascularization, and temporal changes were related to baseline extent of hyperenhancement. The likelihood of functional improvement was inversely related to the SEH during the entire follow-up: at the end of the study period, segments with 1–25, 26–50, 51–75, and 76–100% SEH were 2, 5, 11, and 86 times, respectively, less likely to have functional improvement than segments without hyperenhancement (multilevel analysis, P < 0.001). Although improvement continued over the whole study period in all SEH groups, the time course was significantly more delayed in segments with more extensive hyperenhancement at baseline (multilevel analysis, P < 0.001).
Conclusion
In patients with chronic ischaemic LV dysfunction, improvement of dysfunctional but viable myocardium can be considerably delayed. Both the likelihood and the time course of long-term functional improvement are related to the baseline amount of scar, as visualized by deCMR.
To assess the prevalence of a normal multi-slice computed tomography (MSCT) in patients with suspected coronary artery disease (CAD) and to relate these observations to clinical presentation and pre-test likelihood of CAD.
Methods and results
In total, 340 consecutive patients (182 men, 55 ± 12 years) without a history of CAD who were referred for MSCT angiography were included in the study. Based on patient characteristics and the referral reason for MSCT angiography, patients were classified as having a low, intermediate, or high pre-test likelihood of CAD. Patients were evaluated for the presence of coronary artery calcium as well as the presence of atherosclerosis. Overall, 157 (46%) patients did not have coronary artery calcium and 133 (40%) patients had a completely normal MSCT angiogram. In 58% of the patients with low pre-test likelihood, no coronary atherosclerosis was observed when compared with 33 and 17% of the patients with intermediate and high pre-test likelihood, respectively.
Conclusion
MSCT ruled out coronary atherosclerosis in 40–46% of patients without known CAD who were referred for MSCT. Accordingly, in patients with low-to-intermediate pre-test likelihood, MSCT may be an attractive modality to exclude coronary atherosclerosis and may prevent unnecessary additional functional testing or invasive angiography.
Strain and strain rate (SR) are measures of deformation that reflect left ventricular (LV) function. To our knowledge, no previous study described these indexes in a general population. We therefore described peak-systolic strain and SR of the LV in the general population and derived diagnostic thresholds for these measurements in a healthy subgroup.
Methods and results
In 480 subjects enrolled in a family-based population study (50.5% women; mean age, 50.5 years; 37.2% hypertensive), we measured: (i) end-systolic longitudinal strain and peak-systolic SR from the basal portion of the LV inferior and inferolateral free walls; (ii) radial deformation of the LV inferolateral wall. Longitudinal (mean, 22.9%) and radial (59.2%) strain and longitudinal (1.31 s–1) and radial (3.40 s–1) SR decreased with age (P ≤ 0.007). Longitudinal and radial strain independently decreased (P ≤ 0.006) with relative wall thickness (RWT), longitudinal strain with the waist-to-hip ratio, and radial strain with body weight. In contrast, LV ejection fraction increased (P ≤ 0.0001) with age and RWT. Longitudinal and radial stain rate increased with heart rate (P ≤ 0.05). In healthy subgroup (n = 236), the fifth percentiles were 18.4 and 44.3%, and 0.99 and 2.43 s–1, for longitudinal and radial strain and SR, respectively.
Conclusion
We explored the early signs of LV systolic dysfunction in a general population, using tissue Doppler imaging technique. LV strain and SR decrease with age, body weight, central obesity, and RWT. Our current study resulted in the proposal for diagnostic thresholds for strain and SR, based on a healthy subgroup recruited via random sampling of the population.
To assess the relationship between fish consumption or eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) intake from fish, and (sudden) coronary death.
Methods and results
The impact of recent and long-term fish consumption and EPA+DHA intake on (sudden) coronary death was investigated in the Zutphen Study, a cohort of 1373 men born between 1900 and 1920, and examined repeatedly between 1960 and 2000. Hazard ratios were obtained from time-dependent Cox regression models. The associations between long-term fish consumption, EPA+DHA intake, and (sudden) coronary death were stronger than those of recent consumption. Long-term fish consumption was inversely associated (borderline significant) with coronary heart disease (CHD) death; however, the strength of the association decreased from age 50 [HR: 0.32 (95% CI: 0.13–0.80)] until age 80 [HR: 1.34 (0.58–3.12)]. For men with a daily EPA+DHA intake from fish below 250 mg compared with no intake, CHD death risk was reduced to the same extent as for men with a daily intake above 250 mg (P-value for trend: 0.27). Moreover, long-term fatty-fish consumption lowered the risk of sudden coronary death [HR: 0.46 (0.27–0.78)].
Conclusion
The strength of the association between long-term fish consumption and CHD death decreased with increasing age. Fatty-fish consumption lowered sudden coronary death risk. There was no clear dose–response relationship between EPA+DHA intake and (sudden) coronary death.
Randomized controlled trials (RCTs) have shown that the risk of stroke and venous thromboembolism (VTE) is increased with hormone replacement therapy (HRT); the effect on coronary heart disease (CHD) remains unclear.
Methods and results
RCTs of HRT were identified. Event rates for cerebrovascular disease [stroke, TIA (transient ischaemic attack)], CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE (pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44 113 subjects) were identified. HRT was associated with increases in stroke (odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14–1.53) and VTE (OR 2.05, 95% CI 1.44–2.92). In contrast, CHD events were not increased (OR 1.02, 95% CI 0.90–1.11). Ordinal analyses confirmed that stroke severity was increased with HRT (OR 1.31, 95% CI 1.12–1.54). Although most trials included older subjects, age did not significantly affect risk. The addition of progesterone to oestrogen doubled the risk of VTE.
Conclusion
HRT is associated with an increased risk of stroke, stroke severity, and VTE, but not of CHD events. Although most trials studied older patients, increased risk was not related to age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy.
To assess the efficacy, safety, and long-term results of the balloon angioplasty of recoarctation.
Methods and results
The angioplasty was performed in 99 consecutive patients aged 36 days to 32.6 years (median 268 days). Recoarctation to descending aorta diameter ratio increased from 0.44 (0.35/0.50) to 0.66 (0.57/0.77), P < 0.001. Systolic gradient was reduced from 34.0 (26.0/44.75) to 15.0 (8.25/27.0) mmHg, P < 0.001. In seven patients (7.1%) the procedure was ineffective. One patient (1%) with heart failure died within 24 h after a successful angioplasty and in another (1%) an intimal abruption necessitated surgical revision. The follow-up ranged up to 20.7 years (median 8.1 years). Actuarial probability of survival 20.7 years after the procedure was 0.91, and of reintervention-free survival was 0.44. Older age at the angioplasty was associated with a higher incidence of reinterventions (hazard ratio 1.057; 95% confidence interval 1.012–1.103; P = 0.010). The type of surgery and the recoarctation anatomy did not influence the outcome. In 69 patients aneurysm formation was studied by high-sensitive methods with only one positive finding per 462 patient-years.
Conclusion
Angioplasty is safe and effective regardless of the type of surgery used and the recoarctation anatomy. Older age at the angioplasty is associated with a higher incidence of reinterventions.
Hypertension is a frequent finding in patients with aortic stenosis (AS). However, controversial data about the influence of systemic blood pressure on the quantification of AS have been published.
Methods and results
Various models of AS (plates and biological valves) were studied in an in vitro circuit. Valve areas were calculated with the Doppler continuity equation and the Gorlin formula. Systolic systemic pressures were increased from 80 to 200 mmHg while flow rates were maintained constant. In addition, a computational fluid dynamics (CFD) model was constructed to test the effect of systemic pressures on pressure gradient and valve area estimates.
When systemic pressure was raised, pressure gradients as well as valve areas did not change (mean difference 3.4 ± 1.8 mmHg, range 0.4–6.8 mmHg; mean difference 0.01 ± 0.03 cm2, range –0.02 to 0.05 cm2). By multivariable analysis, neither valve area nor pressure gradient were independently affected by systemic pressure. In addition, CFD analysis revealed no effect of systemic pressure on pressure gradient and valve area.
Conclusion
Our results suggest that blood pressure itself does not directly affect pressure gradients and valve area estimates in AS. Thus, when observed in vivo, these changes are most likely due to afterload-related variations of ejection fraction and, therefore, flow rate.
JAMA current issue JAMA is a weekly primary science, peer-reviewed medical journal published 48 times per year. JAMA publishes original high quality, high impact clinical and research articles on a diverse range of medical topics.
Context Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B12 can lower plasma total homocysteine levels.
Objective To assess the effect of treatment with folic acid and vitamin B12 and the effect of treatment with vitamin B6 as secondary prevention in patients with coronary artery disease or aortic valve stenosis.
Design, Setting, and Participants Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.
Interventions Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B12, 0.4 mg, plus vitamin B6, 40 mg (n = 772); folic acid plus vitamin B12 (n = 772); vitamin B6 alone (n = 772); or placebo (n = 780).
Main Outcome Measures The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.
Results Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B12. The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B12 vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B6 vs 222 (14.3%) not receiving vitamin B6 (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P= .28).
Conclusions This trial did not find an effect of treatment with folic acid/vitamin B12 or vitamin B6 on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.
Context High chronic exposure to inorganic arsenic in drinking water has been related to diabetes development, but the effect of exposure to low to moderate levels of inorganic arsenic on diabetes risk is unknown. In contrast, arsenobetaine, an organic arsenic compound derived from seafood intake, is considered nontoxic.
Objective To investigate the association of arsenic exposure, as measured in urine, with the prevalence of type 2 diabetes in a representative sample of US adults.
Design, Setting, and Participants Cross-sectional study in 788 adults aged 20 years or older who participated in the 2003-2004 National Health and Nutrition Examination Survey (NHANES) and had urine arsenic determinations.
Main Outcome Measure Prevalence of type 2 diabetes across intake of arsenic.
Results The median urine levels of total arsenic, dimethylarsinate, and arsenobetaine were 7.1, 3.0, and 0.9 µg/L, respectively. The prevalence of type 2 diabetes was 7.7%. After adjustment for diabetes risk factors and markers of seafood intake, participants with type 2 diabetes had a 26% higher level of total arsenic (95% confidence interval [CI], 2.0%-56.0%) and a nonsignificant 10% higher level of dimethylarsinate (95% CI, –8.0% to 33.0%) than participants without type 2 diabetes, and levels of arsenobetaine were similar to those of participants without type 2 diabetes. After similar adjustment, the odds ratios for type 2 diabetes comparing participants at the 80th vs the 20th percentiles were 3.58 for the level of total arsenic (95% CI, 1.18-10.83), 1.57 for dimethylarsinate (95% CI, 0.89-2.76), and 0.69 for arsenobetaine (95% CI, 0.33-1.48).
Conclusions After adjustment for biomarkers of seafood intake, total urine arsenic was associated with increased prevalence of type 2 diabetes. This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence. Prospective studies in populations exposed to a range of inorganic arsenic levels are needed to establish whether this association is causal.
Context Neuropsychological tests are used to predict and diagnose dementia. However, to our knowledge, no studies to date have examined whether within-person across-neuropsychological test variability predicts dementia.
Objective To examine whether within-person across-neuropsychological test variability predicts future dementia.
Design The Einstein Aging Study (EAS) is a population-based longitudinal study of aging and dementia located in Bronx County, New York. We used Cox proportional hazards models using age as the time scale to estimate hazard ratios (HRs) for performance on individual neuropsychological tests (Free and Cued Selective Reminding Test, Digit Symbol Substitution subtest of the Wechsler Adult Intelligence Scale Revised, and the Vocabulary subtest of the Wechsler Adult Intelligence Scale Revised) and for within-person across-neuropsychological test variability as predictors of incident dementia. Analyses were stratified by sex, and controlled for education and medical illness.
Setting and Participants A total of 1797 participants (age ≥70 years) enrolled in the EAS between October 1993 and December 2007. Participants seen for the baseline visit only (n = 750), prevalent dementia cases (n = 72), and those with missing follow-up information (n = 78) were excluded. A total of 897 individuals were included in this investigation. Participants had follow-up visits every 12 to 18 months.
Main Outcome Measure Incident dementia.
Results Sixty-one cases of incident dementia were identified during follow-up (mean [SD], 3.3 [2.4] years), of which 26 were in the highest quartile of within-person across-neuropsychological test variability. Adjusting for sex, education, and medical illness, variability was associated with incident dementia (HR for 1-point difference in variability, 3.93 [95% confidence interval {CI}, 2.04-7.56]). The association persisted even after adjusting for level of performance on individual neuropsychological tests (HR for 1-point difference in variability, 2.10 [95% CI, 1.04-4.23]). Comparing Cox models using neuropsychological tests with and without within-person across-neuropsychological test variablity showed that the former improved the prediction of dementia. Sensitivity in a model predicting dementia at 1 year also improved when neuropsychological test variability was included.
Conclusions In this population, within-person across-neuropsychological test variability was associated with development of incident dementia independent of neuropsychological test performance. This finding needs to be confirmed in future studies.
Context Ventilator-associated pneumonia (VAP) causes substantial morbidity. A silver-coated endotracheal tube has been designed to reduce VAP incidence by preventing bacterial colonization and biofilm formation.
Objective To determine whether a silver-coated endotracheal tube would reduce the incidence of microbiologically confirmed VAP.
Design, Setting, and Participants Prospective, randomized, single-blind, controlled study conducted in 54 centers in North America. A total of 9417 adult patients (≥18 years) were screened between 2002 and 2006. A total of 2003 patients expected to require mechanical ventilation for 24 hours or longer were randomized.
Intervention Patients were assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal tubes, similar except for a silver coating on the experimental tube.
Main Outcome Measures Primary outcome was VAP incidence based on quantitative bronchoalveolar lavage fluid culture with 104 colony-forming units/mL or greater in patients intubated for 24 hours or longer. Other outcomes were VAP incidence in all intubated patients, time to VAP onset, length of intubation and duration of intensive care unit and hospital stay, mortality, and adverse events.
Results Among patients intubated for 24 hours or longer, rates of microbiologically confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI], 3.4%-6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95% CI, 5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%] [P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal tube was associated with delayed occurrence of VAP (P = .005). No statistically significant between-group differences were observed in durations of intubation, intensive care unit stay, and hospital stay; mortality; and frequency and severity of adverse events.
Conclusion Patients receiving a silver-coated endotracheal tube had a statistically significant reduction in the incidence of VAP and delayed time to VAP occurrence compared with those receiving a similar, uncoated tube.
