Consider The Evidence: Med/Peds Journal Roundup

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 13, 2006

DREAMing of diabetes prevention. Part I

Filed under: Uncategorized — medblog @ 8:03 pm

NEJM 10/12 – ACE-Inhibitors are pretty much standard of care in diabetics for prevention of nephropathy. But some evidence suggests that angiotensin blockade may have direct beneficial effects on glucose tolerance. An editorial in the latest New England by Ingelfinger and Solomon explains the evidence that led to a trial of ramipril for the prevention of diabetes mellitus. Take note of their mention of potential confounding by the often overlooked fact that thiazide diuretics and B-blockers may promote diabetes – and the ACEIs were often compared to these drugs.
The study by the DREAM trial investigators involved subjects with impaired fasting glucose or impaired glucose tolerance. Subjects were given ramipril or placebo and followed for three years. Unfortunately, it didnt appear to work too well. The incidence of diabetes was similar in both ACEI treatment and placebo groups. However, treatment group patients did show a significantly better response in an oral glucose tolerance test. The trial seems to show that there may well be an effect of RAS blockade on glucose homeostasis, but not enough for primary prevention of diabetes.

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.

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