Clinical Briefs

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.

Looking at CAD through the PERISCOPE

Coronary artery disease (CAD) is the most common cause of death in America, and diabetics suffer a disproportionate burden of risk from cardiovascular disease. Although glucose control has consistently demonstrated a favorable impact upon microvascular diabetic consequences (retinopathy, nephropathy, neuropathy), clinical trials have not been able to convincingly prove favorable effects upon macrovascular endpoints, most importantly CAD.

The PERISCOPE Trial (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) prospectively compared the impact of a sulfonylurea (glimepiride) with a thiazolidinedione (pioglitazone) upon coronary atherosclerosis as measured by intravascular ultrasound (IVUS). To that end, adult type 2 diabetics were randomized to glimepiride or pioglitazone and followed for 18 months.

Percent atheroma volume progressed modestly with glimepiride, and regressed modestly with pioglitazone (p = .002). During the trial, the pioglitazone subjects had a slightly more favorable A1c and HDL than the glimepiride group.

For the first time, it has been demonstrated that a thiazolidinedione has more favorable effects on coronary atherosclerosis than a sulfonylurea. These promising findings about surrogate markers are encouraging, but do not satisfy the remaining uncertainty about whether either class of agent can reduce macrovascular endpoints.

Source: Nissen SE, et al. JAMA. 2008;299(13):1561-1573.

Addressing Agitation and Aggression in Persons with Advanced Dementia

Agitation, aggression, and psychosis are predictably problematic in persons with progressive dementia—over 90% of dementia patients will experience one or more of these during the course of their illness. Indeed, such affective changes are quite often the "straw that breaks the camel's back," resulting in institutionalization because of the unmanageability of such problems in the home setting. Agitation and aggression (A&A) are more commonplace than psychosis, but treatment interventions to prevent or modulate A&A are limited. In addition, the presence of A&A is predictive of a more rapid progression of dementia.

The Neuropsychiatry Inventory (NPI) is a scoring system that contains subitems addressing agitation and psychosis. Study subjects with moderately-severe to severe Alzheimer's disease (n=983) were randomized to memantine (MEM) or placebo and a post-hoc analysis assessed the impact among dementia patients with prevalent A&A.

Memantine was associated with a statistically significant reduction in risk for agitation and aggression. This was not at the expense of functionality, since the Alzheimer Disease Cooperative Study Activities of Daily Living Inventory also showed improvements with memantine compared to placebo. Memantine is promising as a tool for management of aggression and agitation in persons with advanced dementia.

Source: Wilcock GK, et al. Clin Psych. 2008;69:341-348.

It Used To Be Easier To Treat Sinusitis

In the last decade, advice from consensus groups on management of acute sinusitis ranges from exhortation to wisely choose among antibiotics and/or nasal steroids all the way through admonitions against utilization of either. This literature inconsistency helps little to balance the requests of patients who supplicatingly report a history of protracted sinusitis surrendering only to well-chosen antibiotics.

In the United States, more than three-fourths of patients with a clinical diagnosis of sinusitis are prescribed an antibiotic. Young, et al obtained individual patient data from numerous clinical trial databases, including the Cochrane Central Register of Controlled Trials. All trials compared antibiotic to placebo, and reported the percentage of patients cured at trial end. (n=2,547).

The odds ratio for attaining cure by trial end favored antibiotics, but the margin was not large. The number needed to treat (NNT) with antibiotics to be beneficial was 15. The authors suggest that because the benefit of antibiotics is small, a watch-and-wait posture is appropriate for most patients with sinusitis.

Source: Young J, et al Lancet 2008;371:908-914.