Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi, Sankyo, Forest Pharmaceuticals, Lilly, Novo Nordisk, Takeda.

Rifaximin for IBS without constipation

Source: Pimentel M, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011;364:22-32.

It has been recognized for more than a decade that most patients with IBS have abnormal lactulose hydrogen breath tests results, consistent with small bowel bacterial overgrowth. Neomycin treatment, which can re-establish bowel flora, has shown modest efficacy in IBS, but is limited by tolerability issues. Other systemic antibiotics have not provided consistent symptomatic improvement in IBS. A previous pilot trial of rifaximin found that 10 days of treatment provided symptomatic improvement as measured 10 weeks later.

The TARGET trials are two identical double-blind, placebo-controlled trials of subjects with IBS without constipation. Patients were randomly assigned to rifaximin 550 TID or placebo for 2 weeks. Symptoms were monitored for up to 10 weeks. The primary outcome was the proportion of individuals reporting adequate relief of global IBS symptoms. The main secondary outcome was relief of bloating. Additional outcomes included abdominal pain and stool consistency.

Rifaximin provided a statistically significant improvement in global symptoms, bloating, abdominal pain, and stool consistency. Consonant with a very favorable tolerability profile seen in prior clinical trials, the safety profile of rifaximin was similar to placebo in this report. It is anticipated that systemic effects of rifaximin will be rare, since only a miniscule proportion of administered drug enters the systemic circulation.

Short-term treatment with rifaximin can provide statistically significant improvements for patients with IBS without constipation.

Pre-exposure HIV prophylaxis for men who have sex with men

Source: Grant RM, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587-2599.

Men who have sex with men (msm) are a high-risk group for acquisition of HIV, but other than safe sex practices, there has been little encouraging information about chemoprophylaxis. Certainly clinicians have some degree of confidence in the efficacy of post-exposure HIV prophylaxis post-needle stick in the health care setting, but the only population in which pre-exposure prophylaxis has been studied utilized tenofovir vaginal gel in women in Africa, reporting a 39% reduction in HIV infection.

HIV-seronegative men (or transgender women) who have sex with men (n = 2499) were randomized to a combination antiretroviral treatment (emtricitabine and tenofovir) or placebo once daily. They were followed for up to 2.8 years (median 1.2 years).

During follow-up, all subjects were seen every 4 weeks, during which they were counseled on safe sex practices, sexually transmitted diseases (STDs), and STD risk reduction.

At the conclusion of the trial, 36 of 1224 pre-exposure prophylaxis patients sero-converted vs 64 of 1217 placebo subjects (a 44% reduction in HIV incidence). Tolerability of the active antiviral treatment was excellent. The risk reduction demonstrated in this trial seems all the more remarkable because the reduction in unsafe sex practices attributed to the repetitive sexual health education and counseling during the trial would tend to minimize benefits of the medication.

Gait speed and survival in older adults

Source: Studenski S, et al. Gait speed and survival in older adults. JAMA 2011;305:50-58.

The frailty of senior citizens is often portrayed on-stage by slow, stiff gait. This representation may be much more than theatre. Indeed, according to this pooled analysis of a very large data set (34,485 community-dwelling senior citizens), gait speed is linearly associated with mortality among persons age 65 years and older.

Gait speed in the studies was calculated by timing the study subjects while they walked distances varying from 2.4 to 6 meters by simply dividing the distance covered by elapsed time, recorded as meters/second. After obtaining baseline gait speed, study subjects were followed for 6-21 years.

For each 0.1 meter/second increase in baseline gait speed, there was a 12% higher rate of survival. This was independent of gender, BMI, smoking, blood pressure, or self-reported health.

Should clinicians wish to consider using gait speed as a health predictor, the method is simple: The patient is asked to walk over a predetermined distance with the instructions "Walk at your usual pace, as if you were walking down the street." No particular encouragement or stimulus to promote intensification of effort is necessary.