Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Global Consequences of Smoking

In the United States, COPD is the 4th leading cause of death. Widespread public education about smoking toxicity has not decreased COPD mortality, and since 2000 the number of women who die from COPD has eclipsed men.

Worldwide, more men than women suffer toxicity from smoking, with an average life shortening of 22 years for those who succumb to smoking-related disease. Currently, persons in developing countries comprise 82% of all smokers worldwide.

The INTERHEART study is a case-control study which recruited participants from 52 countries in Asia, Europe, the Middle-East, Africa, Australia, and the Americas. The cohorts compared were persons with first acute MI (n = 15,152) and age/sex-matched controls.

The odds ratio for non-fatal MI in current smokers was approximately 3 times that of non smokers. After smoking cessation, this risk was almost halved by 3 years time, but was never reduced to the level of risk of lifelong non-smokers.

Second-hand smoke was also directly associated with increased risk for MI in a graded fashion: even a 'low' level of exposure (1-7 hours/week) was associated with a 24% increased odds ratio for MI, and persons in the highest quartile of exposure (more than 22 hours/week) had a 62% increased odds ratio. Developing countries do not have well established policies to educate the public about health risks of smoking. The majority of life lost in the decades to come will be in developing countries; development of effective cessation programs, public education to prevent the acquisition of a tobacco habit, and heightened public awareness of risks to non-smokers are critically needed.

Teo KK, et al. Lancet. 2006;368:647-658.

Celecoxib for Prevention of Sporadic Colorectal Adenomas

The knowledge that colonic adenoma express tumorigenic cyclooxygenase-2 (COX-2), whereas healthy colonic mucosa does not, led to clinical trials in high-risk populations which have confirmed that COX-2 inhibition reduces colorectal cancer (CCA). For persons with familial adenomatous polyposis, a population with exaggerated CCA risk, celecoxib has shown antitumor activity. Whether the antitumor activity of celecoxib might be useful in prevention of new adenomas for persons who have already had one adenoma detected—but do not have familial adenomatous polyposis—was the subject of this trial.

Patients (n = 2,035) were randomized to receive celecoxib (200 mg b.i.d. or 400 mg b.i.d.) or placebo and were followed for three years, with colonoscopy at years one and three.

Celecoxib was associated with statistically significant reductions in new adenomas: a 33% relative reduction at 200 mg b.i.d., and 38% reduction at 400 mg b.i.d. compared to placebo. Attesting to the elevated risk of new adenomas in this population is the > 60% incidence of new adenomas amongst the placebo group.

Unfortunately, an increase in cardiovascular risk (2.6-3.4 risk ratio increase) was seen in this middle aged population (mean age = 59 years). Although risk reduction for new adeno-mas is evident, competing cardiovascular risk must temper enthusiasm for these favorable results.

Bertagnolli MM, et al. N Engl J Med. 2006;355:873-884.

Trends in Herpes Simplex Prevalence

Early thinking about herpes simplex virus (HSV) simplified pathology into anogenital lesions, which were caused by HSV type 2 (HSV-2), and orofacial lesions which were caused by HSV type 1 (HSV-1). Increasingly, it became clear that either virus could cause lesions at either site, although the preponderance of pathogen-specific sites was still consistent with the earlier thinking. The use of HSV typing was based upon the observation that HSV-1 anogenital lesions have a less frequent recurrence pattern. Although genital HSV-2 is usually sexually transmitted, either type of HSV may be acquired by non-sexual means, and most acquisition is asymptomatic.

Since 1994, overall HSV-2 seroprevalence has declined almost 20% and HSV-1 seroprevalence has decreased 6.9%. On the other hand, there has been a more than four-fold increase in the percentage of individuals whose anogenital HSV is attributable to HSV-1 (ie, they have been diagnosed with genital herpes, but are HSV-2 seronegative), albeit the absolute percentage remains low.

Highly effective antiviral therapies to reduce HSV transmission and recurrences are available, and promising results for an HSV vaccine have been reported. Because HSV-2 infection is associated with increased risk for HIV acquisition, enhanced methods for HSV prevention are a priority.

Xu F, et al. JAMA. 2006;296:964-973.