Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for and serves on the speakers bureaus of Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, Eli Lilly & Co., Novo Nordisk, and Takeda.

Dutasteride reduces prostate cancer risk

Source: Andriole GL, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010;362: 1192-1202.

The prostate cancer prevention trial did not ignite advocacy among clinicians for chemoprevention of prostate cancer (PCA). Although this large trial showed an overall reduction in total cancers (about 23%), high-grade tumors were actually statistically significantly increased. Several reasonable explanations for this phenomenon were offered; however, the disquieting consideration that 5-alpha-reductase inhibitors might be efficacious for reduction of low-grade tumors — but not effective for the more important high Gleason score tumors — remained.

Dutasteride and finasteride are very similar in their effects on the prostate, although there are both pharmacokinetic and pharmacodynamic differences. For instance, dutasteride has a much longer half-life (5 weeks), and dutasteride blocks both arms of the 5-alpha-reductase pathway (types 1 and 2), whereas finasteride only blocks the type 2 pathway. Because both agents are highly efficacious in reducing intraprostatic levels of dihydrotestosterone, the putative culprit in generating BPH and possibly related to development of PCA, many experts consider them clinically comparable.

The REDUCE Trial (Reduction by Dutasteride of Prostate Cancer Events) enrolled men age 50-75 with a PSA of 2.5-10 ng/mL with negative prostate biopsy at baseline. Subjects were randomized to dutasteride 0.5 mg/day or placebo and followed for 4 years, receiving biopsies at year 2 and year 4.

At the completion of the trial, dutasteride was associated with an overall PCA relative risk reduction of 23%; encouragingly, this trial did not show a statistically significantly increased risk of high Gleason score tumors. Because dutasteride also provides favorable symptom benefits for BPH, clinicians may want to re-examine the balance of risks and benefits of 5- alpha-reductase inhibitors.

Zinc and vitamin C for pressure ulcers?

Source: Jamshed N, Schneider JI. Is the use of supplemental vitamin C and zinc for the prevention and treatment of pressure ulcers evidence-based? Annals of Long-Term Care: Clinical Care and Aging 2010;18:28-32.

Elderly patients, particularly those residing in nursing homes, are at risk for pressure ulcers, with recent reviews indicating a nursing home prevalence approximating 10%. Prevention and treatment of pressure ulcers commonly includes zinc and vitamin C, based upon observations (animal studies) that both are necessary for optimum wound healing. Additional support for this concept comes from recognition of the sometimes marginal nutritional status of senior citizens. Some studies have shown malnutrition to result in an increase risk for pressure ulcers by as much as two-fold, but other studies disagree.

For vitamin C, a study performed in the 1970s reported increased wound healing, but the study only contained 20 patients, and subsequent trials have not been able to consistently show similar improvements.

For zinc, one study of senior citizens (n = 672) showed a small but statistically significant difference favoring supplementation, but study design and confounding issues preclude a final word on the subject. Overall, studies have been infrequent, small, and unable to provide a definitive conclusion.

Although generally considered safe, zinc and vitamin C do have associated adverse effect profiles, including increased risk of oxalic acid stones (vitamin C) and copper deficiency (high-dose zinc).

Based upon their literature review, the authors conclude that supplementation of zinc and vitamin C in excess of recommended dietary intake is not supported, and could have important adverse effects.

The role of exercise after bariatric surgery

Source: Evans RK. Maintaining weight loss momentum after bariatric surgery. Am J Lifestyle Med 2010;4:124-127.

Bariatric surgery is increasingly recognized as a rational therapeutic option for morbid obesity and obese patients with comorbidities such as diabetes. On average, bariatric surgery produces a 35% reduction in body weight, but patients regain varying amounts of weight over time. Studies of the role of diet after bariatric surgery have helped to direct long-term postoperative dietary management, but less information is available to guide exercise advice.

In the period after postoperative weight-loss stabilization, the weekly amount of exercise does correlate with sustained weight loss. Unfortunately, 37%-51% of postoperative subjects have been found to be noncompliant with exercise recommendations. Curiously, adherence to exercise in some trial data was greater before surgery than afterward, as if subjects felt they no longer needed exercise to the same degree now that surgery had been performed.

Bariatric surgery does not completely and permanently resolve weight-management issues in obese subjects. The high frequency with which post-surgical patients are noncompliant with exercise recommendations, and, thus, with anticipated weight gain consequences, should spur clinicians to bolster patient education.