More things vitamins dont work for

NEJM 4/27 – Although the precise mechanism for the start of pre-eclampsia is unclear, it has been proposed that oxidative stress is involved in creating the cellular and tissue dysfunction that underlie the syndrome. So naturally, a pilot study of antioxidants to reduce the risk of pre-eclampsia was done by Campbell, et al in 1999. That study showed promising results for the therapy, but futher research contradicted their findings.

Rumbold et al, present a multicenter RCT of nearly 2000 women on the effects of vitamin C and E supplementation in the latest New England. And, just as in most other studies of antioxidants, the supplementation showed no benefits. There was no significant difference in the risk of pre-eclampsia nor in the serious outcomes for the neonate. 

What will the next proposted target for the antioxidant strategy be? We shall see..

Treating *Pre*-Hypertension with ARBs

NEJM – As the benefits of normotension have become clear, the JNC guidlines defining high blood pressure have become more aggressive. The latest revision created a pre-hypertension category of increased risk, in order to stress preventetive measures.

With a high rate of pre-hypertensive patients progressing to hypertension, would medical treatment prevent this change? In the first major study to explore such an option, the latest New England published a article by Julius, et al. testing whether it was feasible to treat pre-hypertension with candesartan.

722 patients with pre-hypertension, tested over three weekly readings, were included in the study. The subjects were randomized to ARB (16mg of candesartan) or placebo. The placebo-control period was two years, followed by a 2 year phase in which all subjects recieved placebo.

During the treatment period 154 pts in the placebo group developed HTN, but only 53 in the candesartan group – a 66% reduction. After the treatment period was over, there was still a 15% risk reduction for the group that had been on the ARB.

Should treating pre-HTN with medication become standard treatment? This study seems to support that conclusion.

Call me on my (benign) Cell

BMJ 4/15 – Hepworth et al. weigh in on the cell phone / brain tumor controversy with a case- control study. Some (poorly interpreted) studies have shown some correlation, so I'm sure this won't end the controversy. Frankly, I'm amazed that they found enough non-cell phone users to do the study. The study compared about a thousand glioma patients with seventeen hundred controls. The cases were matched by age, sex, and geography. All patients were interviewed about the frequency and duration of cell phone use. They conclude "There is generally a lack of convincing and consistent evidence of any effect of exposure to radiofrequency field on risk of cancer…" The group also commented on the fact that their study also found a increased risk in relation to side of use despite an unchanged overall risk – "this finding is probably explained by recall bias, with patients with glioma systematically over-reporting use on the same side as their tumour and consequently under-reporting use on the opposite side." Ambidexterity finally has a downside…

B12 & Folic Acid, lower homocysteine but not cardiovascular risk

NEJM 4/13 – After the correlation between high homocysteine levels and disease such as stroke and MI was discovered, there was a flurry of work looking at the connection. The hope was that the effect was causal, and the simple use of B vitamins would lower homocysteine levels and reduce mortality.

The HOPE-2 investigators published an article exploring whether folic acid and B12 supplementation would lower the risk of cardiovascular events via reduction of homocysteine levels. This was a large study including over 5000 patients. Although the treatment group had significantly lower homocysteinie levels, there were no significant differences between the groups in the rates of death from cardiovascular causes or myocardial infarction.

After the failure of HOPE-TOO to show improved outcomes with vitamin E, this is the second vitamin supplementation study that has not shown a benefit. I guess we will have to wait for the next one to come along….

Grand Rounds is at: Anxiety, Addiction and Depression Treatments

Starve your way to longevity

JAMA 4/13 – For several years, the hottest thing in aging research has been calorie restriction. Animal evidence from several species has demonstrated that severely limiting caloric intake leads to dramatically increased life-spans. The million dollar question is – does it work in humans?

Heilbronn et al. present an article in JAMA that lends credence to the possibility. The evidence is far from direct, and the 6-month study period is far from a lifetime. However, the subjects in the study that underwent calorie restriction showed evidence of a reduction in metabolic rate (via decreased temperature and fasting insulin level) which is thought to lead to the anti-aging effect. There was also less evidence of DNA damage in the calorie restriction group. Interestingly, the effects were not seen in the group that changed to a weight-maintenance diet after losing 15% of body weight – only those that had a continued caloric intake below their baseline energy requirements.

Whether the change in biomarkers will correlate to an actual increase in life-span will have to be studied by a much longer term study – if they can find enough people to be hungry for that long….

I think I'll start linking to grand rounds.

Autism NOT growing in incidence (its not caused by vaccines either)

Pediatrics 4/4 – There have been some concerns about the growing prevalence of autism in the US. Some quacks have even used it as evidence against the safety of childhood vaccines.

Hopefully an article in the latest issue of Pediatrics will help put the issue to rest. Shattuck states "Higher autism prevalence was significantly associated with corresponding declines in the prevalence of mental retardation and learning disabilities" His theory is that it is simply a matter of more children with learning disabilities are being labeled as autistic rather than classified with other  disorders. This model would predict that the number of children placed in the other catergories would have a corresponding decrease – which is exactly what Shattuck found.

And of course, he remembers to mention: "The majority of recent studies have failed to establish a connection between measles-mumps-rubella vaccination or the use of mercury-based vaccine preservative and autism." But i'm sure the fearmongers will not let mere facts deter them…

Donzepil in severe dementia: Not too little too late

Lancet 4/1 – Although Donzepil has been shown to slow the inevitable progression of Alzheimer's dementia (AD), its effects are often subtle, even in mild disease. In the severe stages, it may be difficult to ascertain any benefit, and the drug is often discontinued with the thinking that it is no longer effective.

Winblad et al. studied the efficacy of donzepil in a population with severe AD. They found a significant preseveration in multiple measures of disease and impairment severity including MMSE score. The effects were significant in an intent-to-treat analysis despite a nearly 12% greater level of discontinuation among the Donzepil group.

The study shows a clear benefit to starting donzepil despite advanced disease stage. However, the study did not specifically look at the effect of continuing therapy from the mild stage through the severe stage. The study patients had limited or no exposure to cholinergic inhibitors before the trial, and it remains unclear whether the effect would be similar in patients already on long term therapy.