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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.
Simplifying Dosing for Actinic Keratoses
Source: Zeichner JA, et al. Placebo-controlled, double-blind, randomized pilot study of imiquimod 5% cream applied once per week for 6 months for the treatment of actinic keratoses. J Am Acad Dermatol 2009;60:59-62.
Actinic keratoses (AK) areat bestprecancerous skin lesions, and at worst (a belief held by many leaders in the skin cancer field), skin carcinoma in situ. In either case, the combination of cosmetic burden, troublesome symptoms, and association with squamous cell cancer motivates their destruction. Although it is commonplace to utilize simple local destructive measures (e.g., cryotherapy) to destroy an individual lesion, it is becoming increasingly clear that field therapy (i.e., treating an entire region to include both evident and subclinical AK lesions) provides a better and more lasting service to the patient.
Imiquimod is an immune system up-regulator that has shown excellent efficacy in eradication of AK. As with all other topical agents employed for this purpose, local adverse effects and complexity of dosing regimen are limitations for some patients. Typical dose regimens for imiquimod rely upon 2-3 times weekly application of 5% cream for 8-16 weeks. Less frequent dosing, if effective, would reduce cost, enhance compliance, and possibly be better tolerated.
In this small study (n = 20), subjects applied imiquimod 5% cream once weekly for 16 weeks to half of the face, and placebo to the other half. At 16 weeks, 47% of imiquimod recipients showed marked improvement or better. In contrast to 2-3 times weekly dosing regimens, local adverse effects were essentially absent.
Total clearance rates with more frequent dosing are much higher, but so are intolerance and adverse effect rates. The authors suggest that these favorable results should be stimulus for larger, longer-duration studies.
Aerobic and Resistance Training Effects in PAD
Source: McDermott MM, et al. Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: A randomized controlled trial. JAMA 2009;301:165-174.
The presence of peripheral arterial disease (PAD), confirmed by an ankle-brachial index of < 0.95, is often manifest by limitation in ability to walk, pain with walking, and limitation in performance of normal daily activities. For most patients, smoking cessation is the most important intervention. Pharmacotherapy is of limited value. Exercise training has been suggested as a method to improve oxygen utilization by the tissues and functional ability.
McDermott et al studied PAD patients (n = 156) who were randomized to aerobic training (treadmill), resistance training (weight training), or control. The treadmill group exercised 3 times weekly, beginning at a 2 mph walking speed for 15 minutes, working up to 40 minutes (with increases in speed and grade as tolerated). The resistance training group exercised 3 times weekly with knee extensions, leg presses, and leg curls. Both groups were followed for 6 months. The primary outcome was distance on the 6-minute walk.
Treadmill exercise improved the primary endpoint, but the control and resistance training groups did not significantly differ. Treadmill exercise also improved distant vascular health, as demonstrated by improvements in brachial artery flow-mediated dilation (no improvement was seen in the control or resistance training groups).
Risks Associated with Morning BP Surge
Source: Kario K, White WB. Early morning hypertension: What does it contribute to overall cardiovascular risk assessment? J Am Soc Hypertens 2008;2:397-402.
Ambulatory monitoring of blood pressure (BP) has demonstrated a pattern of BP change typified by an overnight reduction in BP of 10-20% and a "morning surge" in BP beginning closely around the time of awakening. Even in patients with hypertension, morning surge in BP is seen. And it's not only BP that surges in the morning: Blood coagulability, plaque vulnerability, platelet aggregability, and blood viscosity also increase at this time. Because CV events (MI, stroke, arrhythmia) also cluster disproportionately around this circadian phenomenon, experts have opined that modulation of the morning BP surge might provide benefits in clinical outcomes.
The relationship between the morning BP surge and CV risk is strengthened by the observation that it correlates with arterial wall stiffness, left ventricular hypertrophy, and carotid intima-media thickness.
Office blood pressure is typically measured several hours after the morning surge. Encouraging more widespread use of at-home BP self-monitoring is a reasonable first step to obtain more information about morning BP. Since we have not yet learned which, if any, antihypertensives might hold special benefits on morning BP, and we do not have a major clinical trial confirming risk reduction through morning BP control, we lack sufficient evidence to mandate control of morning BP surge as a specific entity at this time.