Asusceptibility testing program was established to determine the prevalence of resistance to penciclovir among herpes simplex virus isolates collected from patients participating in 11 world-wide clinical trials involving penciclovir (topical or intravenous formulations) or famciclovir, the oral prodrug of penciclovir. These trials represented nine randomised double blind, placebo or aciclovir-controlled studies and two open-label studies. Groups surveyed included immunocompetent or immunocompromised patients receiving 2 to 12 months chronic suppressive therapy for genital herpes, immunocompetent patients with recurrent herpes labialis treated for four days, and immunocompromised patients with mucocutaneous herpes simplex virus (HSV). Another subset of patients had been identified as non-responders to aciclovir or to valaciclovir. This program assessed the susceptibility profile for a total of 2145 herpes simplex virus isolates from 913 immunocompetent and 288 immunocompromised patients treated with penciclovir, famciclovir, aciclovir or placebo (depending on trial design). HSV isolates were tested for susceptibility to penciclovir using the plaque reduction assay (PRA) in MRC-5 cells. Resistance was defined as an IC(50)>or=2.0 microg/ml or an IC(50)> 10-fold above the wild type control virus IC(50) within that particular assay. Penciclovir-resistant HSV was isolated from 0.22% immunocompetent patients, and 2.1% of immunocompromised patients overall and therefore the frequency of penciclovir-resistant herpes simplex virus in the immunocompetent population approximates that of aciclovir-resistant herpesvirus reported previously. Penciclovir-resistant HSV isolates were more common in isolates from immunocompromised patients, consistent with aciclovir clinical experience. Treatment with penciclovir (intravenous formulation) was associated with the development of resistant HSV in only one severely immunocompromised patient (day 7 isolate IC(50) = 2.01 microg/ml), although treatment was effective and resulted in the complete clearance of the lesion by day 8. No patients receiving topical penciclovir developed treatment-associated penciclovir-resistant HSV, and a single immunocompromised patient developed resistant HSV upon treatment with oral famiciclovir.

Aims-To compare the eYcacy and safety of famciclovir with aciclovir for the treatment of ophthalmic zoster. Methods-Randomised, double masked, aciclovir controlled, parallel group in 87 centres worldwide including 454 patients with ophthalmic zoster of trigeminal nerve (V 1 ) comprised the intent to treat population. Oral famciclovir 500 mg three times daily or oral aciclovir 800 mg five times daily for 7 days. Assessments included day 0 (screening), days 3 and 7 (during treatment), days 10, 14, 21, 28 and monthly thereafter, up to 6 months (follow up). Proportion of patients who experienced ocular manifestations, severe manifestations and non-severe manifestations; loss of visual acuity was the main outcome measure. Results-The percentage of patients who experienced one or more ocular manifestations was similar for famciclovir (142/ 245, 58.0%) and aciclovir (114/196, 58.2%) recipients, with no significant diVerence between groups (OR 0.99; 95% CI 0.68, 1.45). The percentage of patients who experienced severe and non-severe manifestations was similar between groups, with no significant diVerence. The prevalence of individual ocular manifestations was comparable between groups. There was no significant diVerence between groups for visual acuity loss. Conclusion-Famciclovir 500 mg three times daily was well tolerated and demonstrated eYcacy similar to aciclovir 800 mg five times daily. (Br J Ophthalmol 2001;85:576-581) In 50%-72% of patients with ophthalmic herpes zoster (HZO), involvement of the ocular structures leads to ocular manifestations ranging from self limited processes to chronic ocular inflammation or neuropathy which may lead to visual loss.1-3 The mechanism of ocular manifestations is thought to include active viral replication within the eye and ophthalmic trigeminal nerve, followed by vascular and neural inflammation and damage.Aciclovir treatment for HZO has been shown to be beneficial to patients and is currently the standard of care among health practitioners. [4][5][6] Oral aciclovir at doses of 600-800 mg five times daily for 10 days significantly reduced the acute signs and symptoms of the disease and the incidence of common ocular manifestations such as dendriform keratopathy, uveitis, and stromal keratitis.7 8 However, aciclovir has poor and variable bioavailability requiring high frequency dosing regimens which can lead to diYculties with compliance. Famciclovir is the oral form of penciclovir, a nucleoside analogue which shares the same antiviral spectrum as aciclovir for herpes viruses and has similar potency and selectivity. The oral bioavailability of penciclovir is 77% following administration of famciclovir, 11 significantly higher than the bioavailability of aciclovir (10%-20%).12 In addition, the intracellular half life of penciclovir triphosphate is significantly longer than that of aciclovir triphosphate in cells infected with varicella zoster virus in vitro (1-11 hours for penciclovir triphosphate compared with <1 hour for aciclovir triphosphate). 13Famciclovir is cu...

More than half of all graduate students drop out before graduation. Doctoral students often become mired in the “all but dissertation” (ABD) phase of the process. This grounded theory study focused on the perceptions and experiences of doctoral students in an educational leadership program, who were ABD, regarding their participation in a dissertation-focused intensive writing course called the Dissertation Boot Camp (DBC). Findings revealed participants had particular challenges with time, writing, and advisement. The DBC attended to many of these challenges by providing time, structure, encouragement, and support. Results of the study led to the development of a conceptual framework, which helps to better understand the complexities involved in a student’s pathway to ABD status.

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