Once Daily Valacyclovir for Reducing Viral Shedding in Subjects Newly Diagnosed with Genital Herpes

Objective. Genital herpes (GH) recurrences and viral shedding are more frequent in the first year after initial HSV-2 infection. The objective of this study was to provide the first evaluation of valacyclovir 1 g once daily compared to placebo in reducing viral shedding in subjects newly diagnosed with GH. Methods. 70 subjects were randomized to receive valacyclovir 1 g daily or placebo in a crossover design for 60 days with a 7-day washout period. A daily swab of the genital/anal-rectal area was self-collected for HSV-2 detection by PCR. Subjects attended the clinic for routine study visits and GH recurrence visits. Treatment differences were assessed using a nonparametric crossover analysis. Results. 52 subjects had at least one PCR measurement in both treatment periods and comprised the primary efficacy population. Valacyclovir significantly reduced HSV-2 shedding during all days compared to placebo (mean 2.9% versus 13.5% of all days (P < .01), a 78% reduction). Valacyclovir significantly reduced subclinical HSV-2 shedding during all days compared to placebo (mean 2.4% versus 11.0% of all days (P < .01), a 78% reduction). However, 79% of subjects had no GH recurrences while receiving valacyclovir compared to 52% of subjects receiving placebo (P < .01). Conclusion. In this study, the frequency of total and subclinical HSV-2 shedding was greater than reported in earlier studies involving subjects with a history of symptomatic genital recurrences. Our study is the first to demonstrate a significant reduction in viral shedding with valacyclovir 1 g daily compared to placebo in a population of subjects newly diagnosed with HSV-2 infection

Clinical Study Once Daily Valacyclovir for Reducing Viral Shedding in Subjects Newly Diagnosed with Genital Herpes

Objective. Genital herpes (GH) recurrences and viral shedding are more frequent in the first year after initial HSV-2 infection. The objective of this study was to provide the first evaluation of valacyclovir 1 g once daily compared to placebo in reducing viral shedding in subjects newly diagnosed with GH. Methods. 70 subjects were randomized to receive valacyclovir 1 g daily or placebo in a crossover design for 60 days with a 7-day washout period. A daily swab of the genital/anal-rectal area was self-collected for HSV-2 detection by PCR. Subjects attended the clinic for routine study visits and GH recurrence visits. Treatment differences were assessed using a nonparametric crossover analysis. Results. 52 subjects had at least one PCR measurement in both treatment periods and comprised the primary efficacy population. Valacyclovir significantly reduced HSV-2 shedding during all days compared to placebo (mean 2.9% versus 13.5% of all days (P &lt; .01), a 78% reduction). Valacyclovir significantly reduced subclinical HSV-2 shedding during all days compared to placebo (mean 2.4% versus 11.0% of all days (P &lt; .01), a 78% reduction). However, 79% of subjects had no GH recurrences while receiving valacyclovir compared to 52% of subjects receiving placebo (P &lt; .01). Conclusion. In this study, the frequency of total and subclinical HSV-2 shedding was greater than reported in earlier studies involving subjects with a history of symptomatic genital recurrences. Our study is the first to demonstrate a significant reduction in viral shedding with valacyclovir 1 g daily compared to placebo in a population of subjects newly diagnosed with HSV-2 infection

Superior 2-Year Functional Outcomes Among Young Female Athletes After ACL Reconstruction in 10 Return-to-Sport Training Sessions: Comparison of ACL-SPORTS Randomized Controlled Trial With Delaware-Oslo and MOON Cohorts

Background: Outcomes after anterior cruciate ligament reconstruction (ACLR) are not uniformly good and are worse among young female athletes. Developing better rehabilitation and return-to-sport training programs and evaluating their outcomes are essential. Purpose: (1) Test the effect of strength, agility, plyometric, and secondary prevention (SAPP) exercises with and without perturbation training (SAPP + PERT) on strength, hops, function, activity levels, and return-to-sport rates in young female athletes 1 and 2 years after ACLR and (2) compare 2-year functional outcomes and activity levels among young female athletes in the Anterior Cruciate Ligament Specialized Post-Operative Return-to-Sports (ACL-SPORTS) trial to homogeneous cohorts who completed criterion-based postoperative rehabilitation alone (Multicenter Orthopaedic Outcomes Network [MOON]) and in combination with extended preoperative rehabilitation (Delaware-Oslo). Study Design: Randomized controlled trial, Level of evidence, 1; and cohort study, Level of evidence, 3. Methods: A total of 40 level 1 and level 2 female athletes were enrolled after postoperative impairment resolution 3 to 9 months after primary ACLR. Participants were randomized to 10 SAPP or SAPP + PERT sessions and were tested 1 and 2 years after ACLR on quadriceps strength, hop tests, functional outcomes, and return-to-sport rates. Participants were then compared with homogeneous cohorts of young (<25 years) female athletes who completed criterion-based postoperative rehabilitation alone (MOON) and in combination with extended preoperative rehabilitation (Delaware-Oslo) on 2-year functional outcomes. Results: No significant or meaningful differences were found between SAPP and SAPP + PERT, so groups were collapsed for comparison with the other cohorts. At 2-year follow-up, ACL-SPORTS had the highest scores (P < .01) on the Marx activity rating scale (ACL-SPORTS, 13.5 ± 3.3; Delaware-Oslo, 12.5 ± 2.7; MOON, 10.6 ± 5.1); International Knee Documentation Committee Subjective Knee Evaluation Form (96 ± 7, 92 ± 9, and 84 ± 14, respectively); and Knee injury and Osteoarthritis Outcome Score (KOOS) subscales for Pain (98 ± 4, 94 ± 9, and 90 ± 10, respectively), Symptoms (94 ± 6, 90 ± 9, and 83 ± 14, respectively), Activities of Daily Living (100 ± 1, 99 ± 4, and 96 ± 7, respectively), Sports and Recreation (94 ± 8, 86 ± 15, and 82 ± 17, respectively), and Quality of Life (89 ± 14, 78 ± 18, and 76 ± 19, respectively). The Patient Acceptable Symptom State threshold on the KOOS–Sports and Recreation was achieved by 100% of the ACL-SPORTS cohort compared with 90% of Delaware-Oslo and 78% of MOON (P = .011). Conclusion: Although perturbation training provided no added benefit, 10 sessions of return-to-sport training, compared with criterion-based postoperative rehabilitation alone, yielded statistically significant and clinically meaningfully higher 2-year functional outcomes among young, high-level female athletes after ACLR

Erratum: Global disorders of sex development update since 2006: perceptions, approach and care (Hormone Research in Paediatrics (2016) 85 (158-180) DOI: 10.1159/000442975)

In the appendix of the recent publication by Lee et al. entitled 'Global disorders of sex development update since 2006: perceptions, approach and care' [Horm Res Paediatr 2016;85:158–180, DOI: 10.1159/000442975], Massimo Di Grazia, Psychologist, is incorrectly mentioned to be from Cosenga, Italy. The correct city is Trieste, Italy

The neuroinvasive profiles of H129 (herpes simplex virus type 1) recombinants with putative anterograde-only transneuronal spread properties

The use of viruses as transneuronal tracers has become an increasingly powerful technique for defining the synaptic organization of neural networks. Although a number of recombinant alpha herpesviruses are known to spread selectively in the retrograde direction through neural circuits only one strain, the H129 strain of herpes simplex virus type 1, is reported to selectively spread in the anterograde direction. However, it is unclear from the literature whether there is an absolute block or an attenuation of retrograde spread of H129. Here we demonstrate efficient anterograde spread, and temporally delayed retrograde spread, of H129 and three novel recombinants. In vitro studies revealed no differences in anterograde and retrograde spread of parental H129 and its recombinants through superior cervical ganglion neurons. In vivo injections of rat striatum revealed a clear bias of anterograde spread, although evidence of deficient retrograde transport was also present. Evidence of temporally delayed retrograde transneuronal spread of H129 in the retina was observed following injection of the lateral geniculate nucleus. The data also demonstrated that three novel recombinants efficiently express unique fluorescent reporters and have the capacity to infect the same neurons in dual infection paradigms. From these experiments we conclude that H129 and its recombinants efficiently infect neurons through anterograde transneuronal passage, but also are capable of temporally delayed retrograde transneuronal spread. In addition, the capacity to produce dual infection of projection targets following anterograde transneuronal passage provides an important addition to viral transneuronal tracing technology