Consider The Evidence: Med/Peds Journal Roundup

August 1, 2007

Review: MRSA infection

Filed under: MRSA, NEJM — medblog @ 1:42 am

NEJM 7/26 – Not an original research article, but a worthwhile read. An article by Daum reviews skin and soft tissue MRSA infection in the Clinical Practice section of the current NEJM. An increasingly common issue for which a refresher is always helpful – I thought the paper was so solid it deserved a mention anyway.

Daum, RS. Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med. 2007 Jul 26;357(4):380-90. Review. PMID: 17652653

October 27, 2006

should we screen smokers with serial spiral CTs?

Filed under: lung cancer, NEJM — medblog @ 2:37 pm

NEJM – This weeks New England has been getting alot of publicity for an article by Henschke and other investigators from the Early Lung Cancer Action Project (ELCAP).

In 1993 the ELCAP investigators began the annual screening of asymptomatic subjects that were at high risk for developing lung cancer. Over 27,000 subjects were screened by spiral CT with a positive result in 405 at baseline screening and 74 more over the 12 years that the study ran. 85% of those had stage I cancer with an estimated 10 year survival of 88%. Detection of lung cancer at an early stage  dramatically improves the survival outcome. The authors compared this data to the value of mammography for breast cancer and found it to similar detection rates.

The accompanying ediorial by Unger points out some of the pearls and pitfalls. The study was cohort control rather than RCT, but it was large and multi-center. There is also the question of how to define the “high-risk” population – apparently the criteria varied by center in the study.

From the numbers in the study, it seems as though the biggest yield is from the baseline scan – Im sure there will be further debate about the best interval for screening, among many other details.  But for now the debate is whether this study is enough to justify screening at all….

 N Engl J Med. 2006 Oct 26;355(17):1763-71

October 4, 2006

The Eyes Have It: New therapy for macular degeneration

Filed under: NEJM, opthamology — medblog @ 7:46 pm

NEJM – The discovery of Vascular Endothelia Growth Factor (VEGF) opened the door for the production of many novel pharmaceuticals. The newest drugs to inhibit this factor are not targeted at malignancy, but rather at the destructive angiogenesis that occurs in wet macular degeneration. Now maker Genentech has to do is figure out the price point that people will pay to save their eyesight.

One RCT by Rosenfeld et al. and another by Brown. et al appear in the NEJM, demonstrating the efficacy of Ranibizumab for age related wet macular degeneration.

The Rosenfeld et al. study compared monthly intravitreal injections of the compound agains sham injections for 2 years. They were able to do this because they tested subjects with occult lesions, or predominantly non-classic lesions – which currently have no approved therapy. They found a significant increase in mean visual acutity in the treatment group, while the placebo group had a decrease.

The Brown et al. study tested the drug against verteporfin and laser therapy – the only other approved therapy for predominantly classic lesions. In this head to head trial, more than 90% of subjects in the Ranibizumab group showed delayed progression of the disease, while only 64% in the usual treatment group did so. Again the mean visual acuity increased in the new treatment, while the usual treatment group experienced a decrease.

The next question to answer is whether older anti-VEGF drugs such as Avastin, originally targeted at cancer, will provide a cheaper alternative to produce the same or better effect.

September 4, 2006

Revenge of the COX-2 inhibitors ?

Filed under: cancer, NEJM — medblog @ 8:30 pm

NEJM 8/31 – Results of the VIGOR trial in 2001 shook the medical world with controversy as concern over cardiovascular side effects pushed several COX-2 drugs off the market. Cox-2’s were not only interesting for their anti-inflammatory effect, but also due to evidence of protection from colorectal adenomas – the precursor to colorectal cancer. But studies by both Pfizer and Merck regarding this effect ground to a halt after safety concerns sufaced.

A pair of articles by M. M. Bertagnolli et al. and N. Arber et al. in the New England present data on the prevention of colorectal polyps and adenomas with Celecoxib. Both studies were RCT’s in which the subjects had previous adenomatous lesions removed.

Bertagnolli’s RCT followed over 1800 patients from 1-3 years and compared high and low dose celecoxib therapy to placebo. They found a signficant 33% and 45% risk reduction for the formation of colorectal ademonas with the two groups respectively. The downside was that the risk of cardiovascular effects was 2.6 and 3.4 times higher in the celecoxib groups.

The Arber et al. study had similar results with a 46% risk reduction in adenomas and a 50% risk reduction in advanced adenomas. Serious cardiovascular events occurred in 2.5 percent of subjects in the celecoxib group and 1.9 percent of those in the placebo group (relative risk, 1.30).

Many questions remain about COX-2 inhibitors. Some recent data suggests that these drugs are just as dangerous as non-selective NSAIDs. Also the relative risk of harm varies from 1.3 in the Arber studies to 4 in the VIGOR trial. Hopefully the full story will become clear with further research…

July 30, 2006

Yes to NO for preemies?

Filed under: NEJM, pediatrics, pulmonary — medblog @ 8:14 pm

NEJM 6/27 – Two articles address the controversial use of inhaled Nitric Oxide in pre-term infants. Prior studies have shown that nitric-oxide may improve gas exchange and lung development in neonates with respiratory failure. Ballard et al. tested this hypothesis on infants weighing less than 1250g, while Kinsella et al. studied all infants less than 34 weeks of age with respiratory failure.

While Ballard et al. found a significant reduction in the incidence of bronchopulmonary dysplasia, the effect size was not large (43.9 vs 36.8) and the P value made it just under the wire at 0.042.

Kinsella et al. found no difference in mortality for the overall group, but did find a significant improvement in outcomes for the group weighing between 1000-1250g, as well as improvement in several secondary outcomes.

Clearly there has to be some futher research into what patients will benefit most from this expensive therapy before it becomes standard of care. 

NEJM Vol. 355(4)

July 5, 2006

N-acetylcysteine for Contrast Nephropathy Re-revisited

Filed under: Cardiology, NEJM, renal — medblog @ 10:20 am

NEJM 6/29 – The use of N-Acetylcysteine for contrast nephropathy has been so extensively studied, there are actually meta-analyses of meta-analyses on the subject. And even after all that, the evidence for N-Acetylcysteine for prevention of contrast nephropathy is still pretty much equivocal. For every study that shows a benefit, there is another that shows no benefit at all.

An article in the New England by Marenzi et al. adds weight to the pro-NAc side of the argument. The RCT specifically looked at primary angioplasty and the incidence of contrast nephropathy after the procedure. About 300 subjects were randomized to recieve Low dose NAc, high dose NAc or placebo. According to the study, there was a significant lowering of the incidence of nephropathy with the use of NAc, with the greatest effect in the high-dose group.

Although all patients were hydrated after treatment, I did not find whether the placebo group received a fluid bolus as a control for the NAc solution. Could the effect be related to the extra hydration from the medication solution rather than the NAc itself?

April 27, 2006

More things vitamins dont work for

Filed under: NEJM, ob/gyn — medblog @ 1:37 pm

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..

April 22, 2006

Treating *Pre*-Hypertension with ARBs

Filed under: hypertension, NEJM — medblog @ 7:16 am

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.

April 13, 2006

B12 & Folic Acid, lower homocysteine but not cardiovascular risk

Filed under: CVD, homocysteine, NEJM, stroke — medblog @ 11:11 pm

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….

March 27, 2006

Depression: if at first you dont succeed

Filed under: Depression, NEJM, SSRI — medblog @ 10:18 pm

NEJM 3/23 – Two articles focusing on the pharmacotherapy of depression appear in the New England Journal this week.

Rush et al present a study of 787 patients with depression that had failed to achieve remission with SSRI therapy. The patients were switched from citalopram to either Buproprion, Sertraline, or Venlafaxine. Although approximately one-quarter of the subjects achieved remission after the switch, the rates were about equal among all three drugs. In other words, it did not seem to matter whether the switch was within class, or to a completely new class of drug.

Trivedi et al. present a study examining the commonly used augmentation strategy for treating resistant depression. The study randomized patients on citalopram therapy that had not achieved remission to recieve either buproprion or buspirone as an additional medication. Although about 30 percent of patients in either group achieved remission, the buproprion group had lower depression scores, and a lower dropout rate.

These studies show that switching or adding a medication to treat depression can improve remission rates. However, the factors that determine whether one particular drug will work for a given patient are still a mystery. Until that issue is answered, treatment remains a trial-and-error process. (more…)

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