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.
Postexposure Treatment with Doxycycline and Tick-Borne Relapsing Fever
Borrelia persica is the causative agent of tick-borne relapsing fever (TBRF). The Borrelia name will be familiar to clinicians because of Lyme disease, caused by Borrelia burgdorferi. The tick bite of Ornithodoros tholozani, which may be encountered in environs such as caves, may easily be missed by victims. Incubation of TBRF is 2-18 days. Post-exposure prophylaxis with short-term antibiotic treatment has been shown to be effective for Lyme disease, but no similar data exist from controlled trials to confirm efficacy of treatment for TBRF.
Military training in Israel includes camouflage and survival exercises that take place in an area where TBRF is endemic. Subjects who had participated in this activity (n = 93) were meticulously examined by a physician for signs of tick bite immediately after their potential exposure. In a randomized blinded fashion, subjects received doxycycline daily for 5 days (200 mg day 1, then 100 mg subsequent doses), vs placebo. To ensure consistent drug administration, subjects had direct supervision for each dose.
Ten cases of TBRF occurred in the placebo group, as confirmed by blood smear, and none in the treatment group. As has been seen in other populations, this dosing regimen of doxycycline was well tolerated, with no significant adverse effects.
In this trial, doxycycline was found to be 100% effective when administered within 5 days of exposure to Borrellia persica.
Hasin T, et al. N Engl J Med. 2006;355:148-155.
Secondary Prevention of Stroke: Persistence Pays Off
The benefits of pharmacotherapy for secondary prevention of stroke (SPS) are well established. For instance, warfarin reduces stroke in atrial fibrillation by as much as 60%; aspirin or clopidogrel provide meaningful reduction in recurrent stroke also. Of course, data about successful SPS comes primarily from controlled clinical trials. Ultimately, clinicians and the public alike would like to have insight into the effectiveness of interventions for SPS in the public sector, as well as which factors maximize effectiveness of tools shown to be efficacious in clinical trials.
Shaya et al studied a group selected from the Maryland Medicaid population (n ≥ 400,000), all of whom must enroll in 1 of 8 managed care organizations in that state. Study subjects (n = 925) had been prescribed aspirin, warfarin, or clopidogrel post-stroke. The authors sought to examine the relationship between persistence—consistent renewal of study medication in a timely fashion—and risk of subsequent stroke. The Cox proportional hazards model used in this report is appropriate because it adjusts for factors such as age, race, sex, site of residence, and concomitant medications such as antihypertensive and lipid lowering drugs.
Persistence was associated with a 57% greater likelihood of avoiding a recurrent stroke. As many as 20% of subjects had not been persistent with clopidogrel, aspirin, or warfarin. Clinicians must continue to be vigilant for factors that impair patients' opportunity to persist with medications effectively.
Shaya FT, et al. Am J Manag Care. 2006;12:313-319.
That Darned Cold Sore: What a Difference a Day Makes!
It might come as a surprise that despite numerous methods for treatment of genital herpes, herpes zoster, and mucocutaneous herpes infections in persons with HIV, the antiherpetic antivirals (acyclovir, famciclovir, penciclovir) do not have an FDA approved indication for herpes labialis (HRL), commonly known as the 'cold sore.' Given that the antivirals have shown great success in treatment of recurrences of herpes at other tissue sites, it seems reasonable to suspect that prompt treatment of HRL might be beneficial.
This randomized trial compared famciclovir 1500 mg/d given on one day only, either as 1500 mg single dose, or 750 mg b.i.d., versus placebo. Subjects (n = 711) who had a history of recurrent HRL were instructed to take famciclovir at the earliest prodromal sign, prior to the appearance of skin lesions. They were also to return for clinician evaluation for the next 4 consecutive days.
The primary end point of the study was time to full healing of herpetic lesions. In the placebo group, the mean number of days to healing was 6.2 days. Both single-day famciclovir treatment groups showed greater than 30% reduction in the number of days to heal, with approximately equal efficacy for split-dose or single-dose therapy.
Spruance SL, et al. J Am Acad Dermatol. 2006;55:47-53.