Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance*

ABSTRACT

Background: Episodic therapy of genital herpes is usually recommended for patients with infrequent symptomatic recurrences and where transmission is not a concern. While shorter courses are as effective as standard 5-day regimens, it is unknown whether abbreviated therapy has detrimental effects on natural history and the development of antiviral resistance.

Objectives: To assess time to next recurrence and development of antiviral resistance in patients with recurrent genital herpes treated with either single-day famciclovir (1?g twice-daily) or 3-day valacyclovir (500?mg twice-daily).

Methods: Longer-term, follow-up data on the time to next recurrence and antiviral sensitivity were collected from a previously reported multicenter, multinational, double-blind, parallel group study in which 1179 immunocompetent adults were randomized 1?:?1 to receive either single-day famciclovir or 3-day valacyclovir. Treatment was self-initiated within 6 hours of a recurrence. Swabs for viral culture and sensitivity testing were collected for two sequential recurrences.

Results: The median time to next recurrence from treatment initiation was 33.5 days for famciclovir and 38.0 days for valacyclovir. No drug resistance to penciclovir, the active metabolite of famciclovir, was observed at baseline nor did any develop by the time of the next recurrence.

Limitations: The study had no placebo arm, typing of viral isolates was not performed and viral resistance testing was restricted to penciclovir only.

Conclusion: Treatment with single-day famciclovir for recurrent genital herpes did not shorten the time to the next recurrence. Drug resistance to penciclovir continues to be a rare event in immunocompetent patients.     

Improvement of Oral Bioavailability and Anti-Tumor Effect of Zingerone Self-Microemulsion Drug Delivery System

This study sought to prepare a self-microemulsion drug delivery system containing zingerone (Z-SMEDDS) to improve the low oral bioavailability of zingerone and anti-tumor effect. Z-SMEDDS was characterized by particle size, zeta potential and encapsulation efficiency, while its pharmacokinetics and anti-tumor effects were also evaluated. Z-SMEDDS had stable physicochemical properties, including average particle size of 17.29 ± 0.07 nm, the zeta potential of -22.81 ± 0.29 mV, and the encapsulation efficiency of 97.96% ± 0.02%. In vitro release studies have shown the release of zingerone released by Z-SMEDDS was significantly higher than free zingerone in different release media. The relative oral bioavailability of Z-SMEDDS was 7.63 times compared with free drug. Meanwhile, the half inhibitory concentration （IC50）of Z-SMEDDS and free zingerone was 8.45 μg/mL and 13.30 μg/mL, respectively on HepG2. This study may provide a preliminary basis for further clinical research and application of Z-SMEDDS.     

Neck of femur fractures in the elderly: Does every hour to surgery count?

ObjectivesTo determine if early surgery before 12 h confers a survival or length of stay benefit for patients with neck of femur (NOF) fractures.DesignRetrospective review of prospectively collected data.SettingDistrict general hospital.Patients1913 patients aged over 60 admitted with a fractured NOF who underwent surgery between 2011 and 2015. Mean age was 83.9 years. 73.7% were female.InterventionPatients had surgery for fractured NOF with data collected on demographics, mortality and length of stay.Main outcome measurementsData collected included gender, age, ASA grade, fracture anatomy, surgery, time to surgery, days spent in acute hospital and rehabilitation settings and 30-day mortality. Statistical analysis was used to identify independent predictors of mortality and length of stay.Results30-day mortality was 6.1% and the mean hospitalisation time was 13 ± 11.3 days for the acute hospital and 20.2 ± 17.2 days for the trust. Operations were performed at a mean of 23.8 ± 14.8 h after presentation. Age, gender, ASA grade and type of fracture were independent predictors of either mortality or length of stay. Timing of surgery had an association with mortality but this only reached statistical significance at 24 h.In line with previous studies we analysed time to surgery in 12 h blocks. We also used logistic regression, recognizing time as a continuous variable, which revealed that every hour of delay to surgery increased the mortality risk by 1.8%.ConclusionsWhile every hour of delay increased mortality risk, the association with mortality only became statistically significant when delaying over 24 h. This supports a pragmatic approach, with surgery as soon as medically possible without a race to theatre.Level of evidenceLevel III retrospective cohort study.     

The effects of coronary artery disease severity on time-dependent changes in platelet activation indices in stored whole blood

Background Platelets play a pivotal role in the pathogenesis of the thrombotic complications in cardiovascular disease (CVD). Abnormal platelet activation indices are evolving as potentially useful markers in CVD risk stratification. Whilst there has been some investigation into the effects of storage time on several of these indices, the effects of underlying disease severity on these temporal changes have not been previously studied. Methods Using the ADVIA^TM120 haematology analyser, we assessed the effects of time-dependent storage of whole blood in EDTA, on a number of platelet activation indices: mean platelet volume (MPV), mean platelet component (MPC, measure of platelet density) and platelet component distribution width (PCDW, a marker of platelet shape change. We studied three age- and sex-matched patient groups: (i) healthy controls (n = 10), (ii) stable patients with coronary artery disease (CAD, n = 9); and (iii) patients with acute myocardial infarction (n = 8). Whole blood samples were processed at exactly 5 min following venesection and at 15, 30, 60 and 120 min later in storage in EDTA tubes at room temperature. Results There was a significant and stepwise increase in MPV (P = 0.01) and decrease in PCDW (P = 0.03), with a non-significant trend to increasing MPM and decreasing MPC with increasing underlying disease (that is healthy, ‘stable’ and ‘acute’ artery disease). There was a significant time-dependent increase in MPV and decrease in MPC and PCDW (all P < 0.05), which were all significant on ‘post-hoc’ analyses by 30 min. There were no significant changes in platelet count or MPM with time. There was no interaction of underlying disease with whole-blood storage time for any of the platelet indices reported (P = NS). Conclusion There is a temporal increase in MPV and decrease in MPC and PCDW in venous blood stored over 2 h in EDTA. These changes are not influenced by the underlying CVD disease severity.     

Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging.

AIMS: Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk. METHODS AND RESULTS: In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA. CONCLUSION: The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.     

不同巴曲酶治疗时间窗对急性脑梗死患者脑血管储备的影响

目的 探讨不同时间窗使用巴曲酶治疗急性脑梗死患者对脑血管储备(CVR)的影响.方法 根据发病时间以及治疗方法,123例急性脑梗塞患者分为对照A组(29例,发病12 h以内开始常规治疗)、对照组B组(33例,发病12 h以后开始常规治疗)、治疗A组(29例,发病12 h内常规治疗基础上加用巴曲酶)、治疗B组(32例,发病12 h以后常规治疗基础上加用巴曲酶).对比4组患者治疗前后斯堪地那维亚卒中量表(SSS)评分、大脑中动脉平均血流流速增加值(MFV1-MFV0)、CVR、动脉指数(PI)及两治疗组治疗前后各指标的变化量Δ(MFV1-MFV0)、ΔCVR、ΔPI.结果 治疗后4组患者SSS评分、MFV1-MFV0及CVR较治疗前均升高(P<0.05),PI值较治疗前降低(P<0.05);治疗A、B组治疗后上述指标均优于相应对照组(P<0.05);治疗A组Δ(MFV1-MFV0)、ΔCVR、ΔPI高于治疗B组相应指标(P<0.05).结论 巴曲酶对急性脑梗死患者有显著疗效,能改善患者CVR.早期使用巴曲酶对急性脑梗死患者CVR功能改善作用较为显著,随着时间的推移,疗效降低.