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Despite the salutary effects of ACE inhibitors in heart failure, the effect of this class of agents on aldosterone appears to be transitory. Since aldosterone may affect magnesium and potassium excretion, sympathetic and parasympathetic activation, myocardial and vascular fibrosis, and arterial compliance, interruption of such effects could be of benefit in heart failure. In this trial, Pitt and associates tested the hypothesis that adding an aldosterone antagonist (25 mg spironolactone) to traditional’ heart failure treatment (ACE inhibitor) would reduce mortality. All patients in this trial (n = 1663) suffered systolic dysfunction.
The trial had been designed to last for up to three years; however, mortality reductions achieved by 24 months dictated early closure of the trial. Spironolactone recipients had enjoyed a 35% reduction in risk of death, attributed to reduced mortality from both progressive heart failure and sudden death. Additionally, worsening of heart failure resulting in hospital admission was 35% lower in persons receiving spironolactone. Spironolactone is well known to cause gynecomastia at high doses, but at 25 mg, only 10% of men reported this symptom; hyperkalemia occurred with no greater frequency in the spironolactone group, though the selection criteria for the study did exclude patients with creatinine greater than 2.5—thereby reducing the likelihood of this adversity. Pitt et al conclude that the addition of aldosterone to traditional ACE inhibitor therapy reduces mortality in heart failure patients.
Pitt B, et al. N Engl J Med 1999;341: 709-717.
The ability to safely operate a motor vehicle is significantly compromised when blood sugar drops to levels of less than 65 mg/dL. When type 1 diabetics have undergone driving performance testing with simulators, literally half of persons with glucose levels sufficiently low to be associated with sub-par driving performance did not recognize that they were at a level of hypoglycemia that should prompt consideration not to drive.
In two separate study populations, Clarke and colleagues queried type 1 diabetics on whether they felt safe to drive, at the same time having obtained a blood glucose level. With each blood sugar measured (3-6 times daily), subjects rated on a 6-point scale their perceived level of autonomic activation (e.g., sweating, rapid heart rate) and symptoms of neuroglycopenia (e.g., poor concentration, lightheadedness, lack of coordination). Subjects were also asked to perform and self-evaluate two cognitive function tests and estimate what each of their measured blood glucose results would be. Finally, subjects were asked if they would drive at each time blood sugar was measured.
As many as 47% of subjects whose measured blood glucose was less than 40 mg/dL still felt fine to drive. Even more subjects (60%) stated they would drive when measured glucose was 60-70 mg/dL. Surprisingly, almost 45% of the time when diabetics self-estimated glucose to be within a range they knew to be potentially deleterious to driving performance, they still decided to drive.
Fortunately, type 1 diabetics have not been found to be responsible for any disproportionate segment of auto accidents. Nonetheless, such data should prompt clinicians to reinforce the necessity for close adherence to avoidance of driving during times when hypoglycemia is present.
Clarke WL, et al. JAMA 1999;282: 750-754.
Although there has been the suggestion that sunscreen prevents the development of solar keratoses, there has been, as yet, no proof that sunscreen prevents skin cancer. Intellectually, the concept that beta-carotene might reduce skin cancer risk is appealing since it reduces free radical-induced cellular DNA damage consequent to UV light and has been demonstrated to effectively decrease UV-induced skin tumors in animal studies.
The Nambour Skin Cancer Prevention Trial investigated the effect of sunscreen, beta-carotene, or the combination vs. placebo on skin cancer. The trial enrolled 1621 individuals who were followed for 4.5 years—all residents of Queensland, Australia, an area considered high risk due to its subtropical location. Sunscreen (SPF-16) was applied once daily; 30 mg beta-carotene was administered once daily orally. Study end points were incidence of squamous cell and basal cell carcinoma; each patient was examined on multiple occasions by a dermatologist blinded to study-arm allocation.
The study found a significant 39% decrease in the incidence of squamous cell carcinoma among users of sunscreen but no change in frequency of basal cell carcinoma by any intervention. Overall, there was no skin cancer reduction afforded by beta-carotene; to the contrary, there was a trend toward increase in squamous cell carcinoma with beta-carotene (nonsignificant).
Green A, et al. Lancet 1999;354: 723-729.