By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is a retained consultant for Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, Janssen, Lilly, Novo Nordisk, Pfizer, and Sanofi.
Post-Stroke Blood Pressure Targets: Recent Lacunar Stroke
Source: The SPS3 Study Group. Lancet 2013;382:507-515.
Cerebral infarction related to small vessel disease, known as lacunar stroke, is strongly associated with hypertension (HTN). Numerous clinical trials have confirmed that control of HTN provides substantial stroke reduction overall (≥ 40%), without specifically distinguishing the effects on lacunar stroke.
The Secondary Prevention of Small Subcortical Strokes trial compared two levels of systolic blood pressure (SBP) among patients with a recent MRI-confirmed lacunar stroke for impact on recurrent stroke. Because of concern that excessive SBP lowering in the face of acute cerebral ischemia might be detrimental, subjects were randomized at least 2 weeks after the identifying event. Subjects (n = 3020) were randomized to one of two groups: SBP goal 130-149 mmHg or SBP goal < 130 mmHg. Clinicians were allowed to use whatever medications they preferred to attain SBP goals.
At 3.7 years, there was no statistically significant difference in the primary outcome of the study: all stroke. On the other hand, a secondary endpoint (which must be considered "hypothesis generating" since the primary endpoint failed) of hemorrhagic stroke was reduced by almost two-thirds in the SBP < 130 group. This finding prompted the consideration by the authors that since there was no difference in overall outcomes, but the suggestion of substantial reduction in hemorrhagic stroke by more strict blood pressure control, some clinicians might consider the more stringent SBP at least potentially beneficial.
Wedge Insoles for Knee Osteoarthritis: Probably Not
Source: Parkes MJ, et al. JAMA 2013;310: 722-730.
In the united states, osteoarthritis is the No. 1 cause of disability. The "graying" of America, in concert with an ever-growing prevalence of obesity, portends an equally expanding population of osteoarthritis.
Osteoarthritis of the knee (OA-K) can be particularly disabling, and currently available medical treatments, such as NSAIDs, topical analgesics, and opioids, each have limitations. Hence, short of surgical intervention, alternatives — such as non-pharmacologic treatment — are sought.
Medial OA-K is one of the most common subtypes. In theory, load reduction on the medial compartment might alleviate symptoms, disease progression, or both. By placing an angulated wedge under the sole of the foot, such load reduction can be achieved. A meta-analysis was performed (n = 885) by Parkes et al to evaluate the efficacy of mechanical interventions intended to unload the medial knee compartment including wedges or structured shoes.
Overall, studies did confirm a positive effect of devices to unload the medial compartment, although the effect size was not large. Additionally, trials with an active control (such as a neutral vs an offloading wedge) failed to confirm positive effects. These mixed results call into question whether clinicians can be confident in the efficacy of wedge insoles.
Can We Identify Persons on Zolpidem at Risk for Driving Mishap?
Source: Farkas RH, et al. N Engl J Med 2013;369:689-691.
Benzodiazepines can impair consciousness. It has been recognized that the elderly — and anyone with renal impairment because they metabolize zolpidem (ZOL) more slowly — should receive a lower dose (ZOL 5 mg) than other adults (ZOL 10 mg). Soon after the advent of immediate-release ZOL, a controlled-release formulation became available. Prospective studies of ZOL indicated that plasma levels > 50 ng/mL were associated with impairment in driving skills. As formulations of ZOL evolved, pharmacokinetic studies found that the 10 mg approved dose of immediate-release ZOL was associated with ZOL levels > 50 ng/dL in as many as 15% of women (who metabolize ZOL more slowly).
Recognition of the potential for ZOL to produce impairment in driving has resulted in FDA recommendations for dose reductions in various ZOL formulations, especially in women.
Insomnia and other sleep disorders are, of course, associated with an increased risk of auto accidents due to excessive daytime sleepiness. Clinicians should maintain vigilance that appropriate dose limitations are observed — since patients often do not perceive the impairment induced by benzodiazepines — and that patients do not drive sooner than the recommended interval after taking their dose of medication.