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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.
Metabolic Effects of Topiramate in Obese Diabetics
Almost 90% of persons with type 2 diabetes (DM2) are overweight. Weight loss in DM2 consistently results in meaningful favorable changes in lipids, glucose, and insulin resistance, so the clinical community embraces tools to enhance weight loss in this population.
Unfortunately, currently available weight-loss tools (eg, orlistat, sibutramine) are limited by modest long-term impact, tolerability, and cost. Diet and exercise are highly effective as demonstrated in clinical trials, but most patients do not enjoy the "team" approach available in such trials, resulting in failure to achieve and maintain weight loss goals.
In clinical trials of immediate-release topiramate (TOP-IR) for migraine, weight loss has been consistently identified, in the absence of any dietary or exercise intervention. Similarly, TOP-IR has demonstrated weight loss in trials of DM2, but has had tolerability issues. Controlled release topiramate (TOP-CR) has been developed for greater ease of administration (qd vs b.i.d.) and lesser adverse effect profile.
DM2 subjects (n = 111) were randomized to diet and exercise with or without TOP-CR; approximately ¾ of both groups were also on metformin. At 16 weeks, endpoints favored the group with TOP-CR: weight loss (6.0 kg vs 2.5 kg), A1C (6.7 vs 7.1), and BP (117/74 vs 124/77). But because of the profile of adverse events (43% of participants on TOP experienced central nervous system or peripheral nervous system effects) it is unlikely that current formulations of TOP will have a role in metabolic management of diabetes.
Rosenstock J, et al. Diabetes Care. 2007;30(6):1480-1486.
Clues that Differentiate Toenail Onychomycosis from Look-alikes
It is tempting to initiate pharmacotherapy when the appearance of a pathologic nail suggests onychomycosis (ONYC). However, systemic treatments for ONYC require a protracted course of therapy, at substantial expense, with potential toxicity, leading to expert advice which suggests not initiating treatment unless the presence of fungus has been confirmed, eg, by KOH examination, fungal culture, or both.
A variety of other disorders may mimic ONYC, including psoriasis, lichen planus, and post-traumatic dystrophy. Seeking to discern factors which correlate with the presence of ONYC, Walling et al reviewed characteristics of 150 cases of ONYC confirmed by PAS staining.
The factors that best correlated with confirmed fungal infection included male gender, age over 64, concurrent tinea pedis, and involvement of the third or fifth digit. Dystrophic changes of the great toe were the most commonly noted finding, but only in half of cases of dystrophic changes of the great toe was fungus confirmed. Female gender was a negative predictor.
Because current methodologies for confirmation of fungal infection are imperfect, cases which test negative for fungi but are associated with positive correlation factors should be considered for repeat testing.
Walling HW, Sniezek PJ. Am Acad Dermatol. 2007;56:945-948.
Comparing Medical and Surgical Management of Sciatica
Low back pain (LBP) remains one of the most commonplace and costly disabilities affecting working Americans. Although there is some controversy about appropriate indications for surgery, the presence of persistent sciatica (SCI)—peripheral pain that is indicative of a lumbar or sacral nerve compression—is commonly used as a selection criterion for consideration of surgical intervention. There is little data to compare outcomes for persons with SCI treated with conservative treatment versus surgery. Some guidelines suggest that surgical treatment be considered for persons with SCI persistent after 6 weeks of conservative therapy.
Subjects (n = 283) with SCI rated as severe due to incapacitating pain were enrolled in this trial if symptoms persisted 6-12 weeks, and were randomized into early surgery (within the next 2 weeks) or conservative management. A small percent of persons assigned to surgery (11%) experienced resolution within the 2-week waiting period for surgery. Because of persistent or worsening symptoms, 39% of the group randomized to conservative treatment underwent surgery. Outcomes of the trial included degree of functional disability, intensity of leg pain, and overall perceived degree of recovery, as assessed periodically over 1 year.
Symptom relief was more prompt in the surgical group. However, at 1 year the degree of functional recovery, as well as the other outcomes measured were the same in both groups.
Rapid pain relief may be critical in some cases. If pain management can be satisfactorily achieved without surgical intervention, it appears that conservative treatment offers similar overall outcomes.
Peul WC, et al N Engl J Med. 2007;356:2245-2256.