Luteal support with a vaginal progesterone formulation has comparable clinical outcomes to an intramuscular (IM) delivery method, reported researchers at the American Society for Reproductive Medicine (ASRM) 64th Annual Meeting.

Currently, patients undergoing fertility therapy have many formulation options for their medications. Research presented here examined the effectiveness of a vaginal formulation of progesterone when compared with the more traditional IM dosing.

Researchers enrolled 544 women who were undergoing treatment for in vitro fertilisation and embryo transfer (IVF-ET). Study participants were divided into 2 groups: 145 women received vaginal micronised progesterone and 399 women received standard IM progesterone. They received a gonadotropin-releasing hormone for pituitary down-regulation as part of what is known as the long protocol for IVF-ET.

Embryo transfers were performed during either the cleavage or the blastocyst developmental stages.

Women in the study were aged 33 years on average in the treatment cohort and 34 years in the control cohort.

Results demonstrated that pregnancy outcomes were similar for the 2 groups, with clinical pregnancies in 49% and 53% of women, respectively. The groups also experienced similar rates of miscarriage (8% vs 10%). No statistically appreciable differences were observed in the number of oocytes retrieved (13 vs 14) and in the mean number of embryo transfers (2.4 vs 2.6). All these differences were statistically nonsignificant.

Based on these findings, the authors concluded that luteal support with vaginal progesterone has comparable clinical outcomes to IM delivery.

The 2 formulations have similar clinical outcomes, but obviously, the vaginal administration may be more convenient, summarised researchers.

In the most comprehensive meta-analysis to date, researchers have shown fever is strongly associated with worse outcomes in stroke and other types of neurological injury across multiple outcome measures.

Investigators at Massachusetts General Hospital , in Boston , analyzed data from 39 studies that included 14,431 patients with stroke and other brain injuries. Patients in the selected studies included individuals who had ischemic and hemorrhagic stroke and neurological ICU populations including traumatic brain injury (TBI) patients.

Outcome measures included clinical, functional, and economic outcomes as assessed by mortality, the Glasgow Outcome Scale (GOS), Barthel Index, modified Rankin Scale (mRS), Canadian Stroke Scale (CSS), ICU length of stay (LOS), and hospital LOS.

Collectively, the meta-analyses presented a consistent result. In each of the 7 outcome measures evaluated, the meta-analysis indicated that fever/higher body temperature was significantly associated with worse outcome as indicated by higher mortality rate, greater disability, more dependence, worse functional outcome, greater severity, and longer stays in the hospitals and the ICU.

The investigators report the effect size of fever/higher body temperatures ranged from moderately small for the GOS to large for mRS, ICU LOS, and hospital LOS. In addition, in comparison with individuals with stroke or TBI who did not have fever/higher body temperatures, their counterparts with fever had a 1.3 to 3.2 times odds of a longer hospital LOS. The results also suggest fever is associated with greater mortality and greater neurological dysfunction in patients with neurological injury.

Whether fever actually causes worse outcomes or whether it is largely an effect of other causative factors is beyond the scope of this study. However, the investigators point out it is noteworthy that no other covariate examined comes close to reaching the consistency of significance found with fever/higher body temperature.

According to the authors, the current findings point to a need for a major prospective, randomized study to confirm whether aggressive efforts to prevent and control fever in neurologically injured patients improves outcomes. Studies are currently ongoing for using induced hypothermia for such conditions as ischemic stroke and traumatic brain injury.

Source: Stroke 2008; 39: 3029-35

The potential benefits of inhaled corticosteroids for the treatment of acute asthma exacerbations include direct delivery to the airways and reduced systemic exposure. However, their effect in young children is still controversial.

This study conducted by Benjamin Volovtiz et al compared the effect of inhaled budesonide and inhaled fluticasone in controlling acute asthma exacerbations in young children at home.

In a quasi-randomized crossover design, children aged 5 months to 5 years with severe recurrent asthma episodes were treated either with inhaled budesonide 200 mcg or inhaled fluticasone 125 mcg delivered with a similar spacer.

At the onset of asthma exacerbations, two puffs of inhaled terbutaline followed by inhaled budesonide or fluticasone was administered using one of the following treatment protocols:

(1) 4-day protocol for a relatively mild exacerbation;

(2) 8-day protocol for exacerbations that were more severe or uncontrolled by the 4-day protocol; and

(3) 8-day protocol + azithromycin for exacerbations uncontrolled by the 8-day protocol or possibly associated with infection with atypical agents.

Children were followed for 2 months after each exacerbation. Good response was defined as the absence of asthma symptoms for at least 2 weeks from completion of treatment.

One hundred children were recruited: 36 were treated with budesonide, 21 with fluticasone, and 44 with both on different occasions. The groups were similar for preliminary data.

Good response was noted in 87% of the budesonide group, 85% of the fluticasone group, and 86% of the budesonide/fluticasone group. By protocol, rates of good response were 84%, 83%, and 94% for the 4-day, 8-day, and 8-day+azithromycin treatment protocols, respectively; corresponding symptom-free periods after treatment were 4.0, 4.9, and 4.3 weeks. None of the children received oral corticosteroids.

Acute asthma exacerbations in young children can be effectively controlled at home with the use of high repetitive doses of inhaled budesonide or inhaled fluticasone, initially together with beta 2 agonists, given at the beginning of the attack, for a period of 4–8 days.

Source: Journal of Asthma 2008; 45:561–567.

A new observational study found an association between higher levels of nonfasting triglycerides and increasing risk for ischemic stroke.

The results, together with those from 2 previous studies, suggested that elevated levels of nonfasting triglycerides and remnant lipoprotein cholesterol could be considered together with elevated levels of low-density lipoprotein cholesterol for prediction of cardiovascular risk, said the researchers.

Triglyceride levels are usually measured in a fasting state, which would exclude most remnant lipoproteins; however, except for a few hours in the morning, most individuals are in a nonfasting state most of the time, added researchers.

"Therefore, by mainly studying fasting rather than nonfasting triglyceride levels, several previous studies may have missed an association between triglycerides and ischemic stroke," wrote researchers. "Also, because former studies mainly focused on moderately elevated levels of triglycerides, an association of very high levels with risk of ischemic stroke could have gone unnoticed."

The current study used data on 13,956 men and women enrolled in the Copenhagen City Heart Study, a prospective, population-based study begun in 1976, with follow-up through July 2007. In this study, the researchers looked at baseline levels of nonfasting triglycerides, other risk factors at baseline and follow-up examinations, and the incidence of ischemic stroke.

They also carried out a cross-sectional study of 9637 participants in the prospective study who attended the 1991-1994 examination, since levels of nonfasting remnant lipoprotein cholesterol as well as the lipid profile were measured at that examination, the authors note. In the cross-sectional study, they looked at levels of nonfasting triglycerides, remnant cholesterol, and the prevalence of ischemic stroke.

Of the 13,956 participants in the prospective study, 1529 had an ischemic stroke during follow-up. Researchers observed an increased risk for ischemic stroke with increasing levels of nonfasting triglycerides, both in men and in women.

After adjustment for conventional cerebrovascular risk factors, for age, body mass index, and diabetes mellitus, and finally adjusting for age and high-density lipoprotein cholesterol level, risk estimates were only attenuated slightly,. noted researchers.

The absolute 10-year risk for ischemic stroke ranged from 2.6% in men younger than 55 years with nonfasting triglyceride levels of less than 89 mg/dL to 16.7% in those with levels of 443 mg/dL and higher. The corresponding values for women were 1.9% and 12.2%.

In the cross-sectional study, researchers found nonfasting triglyceride levels were highest in those who had a previous ischemic stroke in both men and in women vs the control groups. Likewise, noted researchers, levels of remnant cholesterol were highest in those who developed ischemic stroke in both men and women.

This led to the final conclusion that nonfasting triglycerides as a marker of remnant cholesterol were associated with increased risk of ischemic stroke, with the risk being 3 times higher in men and 4 times higher in women, concluded researchers.

Source: American Heart Association Scientific Sessions; New Orleans , Louisiana , USA : 8–12 Nov 2008

The American College of Cardiology and the American Heart Association have jointly released a comprehensive set of practice guidelines to assist cardiologists in making everyday clinical decisions for adult patients with congenital heart disease (CHD).

The guidelines provide comprehensive information on the clinical features; diagnosis; and medical, surgical, and interventional therapy of a range of congenital heart defects.

They also point out common problems and pitfalls; highlight key issues to look for during follow-up; and make recommendations on genetic testing, pregnancy, contraception, and physical activity.

In addition, the guidelines call for:

• Coordination of the ongoing care of patients through regional centres of excellence with expertise in adult congenital heart disease
• Individual and family counseling, including early education of children on their heart condition and what to do to stay healthy
• A formal transition process to help teenagers and young adults cross the bridge from their paediatric cardiologist to an adult cardiologist
• Outreach and education programmes to bring patients back into the healthcare system if they are no longer receiving appropriate care and follow-up
• Education about the risks of infection of the inner lining of the heart or the heart valves posed by dental procedures, tattoos, body piercings, and other procedures that may introduce bacteria into the bloodstream
• Thorough clinical evaluation of patients before noncardiac surgery or any procedure requiring anaesthesia or sedation, coordinated through a regional centre of excellence
• Counseling about safe contraception
• Consultation before pregnancy, including genetic counseling, so that patients understand the risks to both mother and baby

Source: J Am Coll Cardiol. Published online November 7, 2008