CARDIOVASCULAR DISEASE IN WOMEN IS UNAFFECTED BY FOLIC ACID AND B VITAMINS

Folic acid and B vitamins have no beneficial effect on cardiovascular events among women at high risk for cardiovascular disease, despite lowering homocysteine levels, according to Christine M. Albert, MD, of the Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

In a report published in the May 7 JAMA, 5,442 female health professionals 42 and older with preexisting cardiovascular disease (defined as reported history of myocardial infarction, stroke, coronary or peripheral revascularization, angina pectoris, or transient ischemic attack; 64.2% at baseline) or at least three cardiac risk factors (diagnosed hypertension, high cholesterol, diabetes mellitus, parental history of premature myocardial infarction, obesity, or current cigarette use) were given a pill containing folic acid (2.5 mg/d), vitamin B₆ (50 mg/d), and vitamin B₁₂ (1 mg/d) or a matching placebo for 7.3 years.

Average adherence, defined as taking at least two-thirds of the study pills, was approximately 83% for both groups. At follow-up, 406 (14.9%) treatment participants had at least one cardiovascular event, compared with 390 (14.3%) controls (relative risk [RR], 1.03); overall, there were 139 myocardial infarctions, 148 strokes, 508 coronary revascularization procedures, and 190 cardiovascular deaths.

Secondary total coronary heart disease events occurred in 283 participants in the active treatment group and in 280 in the placebo group (RR, 1.00). There were no significant differences in myocardial infarction (RR, 0.87), stroke (RR, 1.14), or cardiovascular mortality (RR, 1.01) between groups.

In a blood substudy, median folate levels among the subjects in treatment and control groups (150 each) were similar at baseline (8.9 and 8.8 ng/mL, respectively). Levels for both groups increased at follow-up; 49.3% of participants in the active treatment group had a folate level greater than 40 ng/mL, compared with 4.7% in the control group. There were no reductions of median homocysteine levels in the placebo group (baseline, 12.5 μmol/L; follow-up, 11.8 μmol/L). However, levels were significantly reduced in active treatment subjects (baseline, 12.1 μmol/L; follow-up, 9.8 μmol/L). The researchers noted that the geometric mean homocysteine level was decreased by 18.5% among those who received treatment, compared with the level found in the placebo group.

Suggested Reading
Albert CM, Cook NR, Gaziano JM, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008;299(17):2027-2036.

CORTICOSTEROIDS HAVE NO EFFECT ON MORTALITY IN CHILDREN WITH BACTERIAL MENINGITIS

Adjuvant corticosteroid therapy does not decrease the risk of mortality in children with bacterial meningitis and has no effect on the length of hospital stay, according to research published in the May 7 JAMA.

Jillian Mongelluzzo, of the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine, and colleagues analyzed the use of adjuvant corticosteroids in 248 (8.9%) of 2,780 discharged children (younger than 18; mean age, 3.4) with bacterial meningitis. The most commonly used corticosteroid was dexamethasone, administered to 75% of recipients.

There was no significant difference in number of deaths among the children who received corticosteroids (15 deaths; 6%), compared with those who did not receive the drugs (102 deaths; 4%). The overall mortality rate was 4.2%. There was no association between adjuvant corticosteroid use and time until death (hazard ratio [HR], 1.18) or time of hospital discharge (HR, 0.89), when excluding children in the highest and lowest quintiles of propensity scores. For subjects with pneumococcal meningitis (n = 199) and meningococcal meningitis (n = 86), there was no difference in time to death (HR, 0.69) or time to hospital discharge (HR, 0.95) between treatment and nontreatment groups. Nor did time to death change when assessing children with meningitis caused by either Streptococcus pneumoniae (HR, 0.53) or Neisseria meningitidis (HR, 1.39). Length of hospitalization was not significantly different when stratified by these organisms (HRs, 1.03 and 0.70, respectively). The median length of hospitalization for children who received corticosteroids was 12 days, while the median length for children who did not receive the corticosteroids was 10 days.

The authors noted that result discrepancies from studies involving adults may be due to different predisposing factors for meningitis or inflammatory responses, as well as an increased case fatality rate for pneumococcal meningitis (34% for adults and 4.2% for children). “Our study could have been underpowered to determine a difference in mortality when case fatality rates are low in children with bacterial meningitis,” the researchers stated. Small subgroups made it difficult to determine significant differences and hard to ascertain benefits in subpopulations of patients. The investigators expressed the need for further research of adjuvant corticosteroid therapy on improvement of the long-term quality of life in some children with bacterial meningitis.

Suggested Reading
Mongelluzzo J, Mohamad Z, Ten Have TR, Shah SS. Corticosteroids and mortality in children with bacterial meningitis. JAMA. 2008;299(17):2048-2055.

NEW MRI ANALYSIS PREDICTS LONG-TERM OUTCOME OF DIFFUSE AXONAL INJURY

Diffusion tensor tractography–based quantification of MRIs acted as an indicator of diffuse axonal injury at an early stage and may predict long-term outcome, according to a study published in the May Archives of Neurology.

Jun Yi Wang, MS, of the Department of Cognition and Neuroscience, University of Texas at Dallas, and colleagues analyzed MRIs from 12 patients with severe closed-head traumatic brain injuries who had a mechanism consistent with diffuse axonal injury approximately seven days after injury, as well as from 12 age- and sex-matched healthy controls. Six fiber variables of the corpus callosum (CC) were obtained; Glasgow Outcome Scale–Extended (GOSE) scores were assessed nine months postinjury in 11 of the 12 patients.

Using diffusion tensor imaging, researchers found that “at least one fiber variable of the whole corpus callosum, all subareas of the corpus callosum and peduncular projections, and the fornix body were significantly different between the patients and controls, with patients showing worse measures.” At least one fiber variable of the whole CC, CC2, and CC4 had strong positive correlations with GOSE scores. The Spearman rank correlation was also positive between partial least square regression predicted and actual GOSE scores for the fixed effects and random effects models (0.91 and 0.63, respectively).

All patients had at least one white matter hyperintensity on their fluid attenuation and inversion recovery (FLAIR) images. This diffusion tensor imaging index correlated marginally with the GOSE score and was not statistically significant.

The researchers concluded that “tractography-based quantification may be more useful than FLAIR lesion volume analysis and factors such as age, sex, initial Glasgow Coma Scale score, and Trauma Coma Databank computed tomography classification in prognosis.” However, they cautioned that this technology is relatively new, and the fiber assignment by continuous tracking algorithm used in diffusion tensor imaging Studio has limitations in the areas of crossing fibers. “Failure or early termination in fiber propagation or fiber jumping onto another tract may exist,” the investigators stated. Other limitations were the small sample size and the inclusion of only a subset of white matter structures at risk.

Suggested Reading
Wang JY, Bakhadirov K, Devous MD Sr, et al. Diffusion tensor tractography of traumatic diffuse axonal injury. Arch Neurol. 2008;65(5):619-626.

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