Orit Peled

Bio: Orit Peled is an academic researcher from Tel Aviv University. The author has contributed to research in topics: Internal medicine & Valganciclovir. The author has an hindex of 5, co-authored 7 publications receiving 77 citations.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study.

Abstract: BACKGROUND Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens. METHODS The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated. RESULTS Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given. CONCLUSIONS The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.

LB20. Valacyclovir to Prevent Vertical Transmission of Cytomegalovirus After Maternal Primary Infection During Pregnancy

Abstract: Background Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. The highest risk of fetal injury follows a maternal primary infection early in pregnancy. Despite the potential for severe fetal injury, to date there are no proven means to prevent viral transmission. Valacyclovir is an antiviral drug proven effective in decreasing the risk for CMV infection among transplant recipients. Valacyclovir is safe for use in pregnancy, and concentrates in the amniotic fluid without accumulating. A dose of 8 g/day creates therapeutic drug levels in the amniotic fluid and fetal blood.

Social isolation in mice: behavior, immunity, and tumor growth.

Abstract: The aim of this study was to investigate the behavioral, immunological, and neurological effects of long-term isolation in an animal model. Male C3H/eB mice wereraised in either social isolation or...

Efficacy and Safety of a Weight-based Dosing Regimen of Valganciclovir for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients.

Abstract: Background Valganciclovir has been widely used for cytomegalovirus (CMV) prophylaxis in solid-organ transplant recipients. However, the optimal dosing protocol and target exposure in children are still unclear. Specific data as to the efficacy and safety of low-dose/low-exposure regimens are lacking and urgently needed. Methods During 2010 to 2015, the clinical efficacy and safety of a weight-based regimen of valganciclovir of 17 mg/kg/day, with a stratified dose reduction for impaired creatinine clearance, given as a CMV prophylaxis for 3 to 6 months, was retrospectively evaluated among pediatric kidney and liver transplant recipients, 12 months posttransplantation. Incidence of CMV infection was assessed by periodic measurements of viral load; adverse events were evaluated. Results Eighty-three children who had undergone 86 transplantations and were treated with 17 mg/kg of valganciclovir were included. Median age was 9.77 years (range, 0.6 to 18.9). Twelve (14%) developed CMV infection: 1 during prophylaxis and 11 during follow-up. These events comprised 6 cases of asymptomatic viremia and 6 cases of a clinically significant disease without occurrences of tissue-invasive disease. Treatment-related adverse effects occurred in 7 patients (8%), mostly hematological, resulting in premature drug cessation. Conclusions Our results support the use of 17 mg/kg of valganciclovir for CMV prophylaxis in liver and kidney transplanted children as it showed satisfactory long-term efficacy and a good safety profile.

Cytomegalovirus感染症 (ウイルス(特集))

Abstract: The most common disease manifestation is gastrointestinal disease. CMV pneumonia is the most serious complication but has become less common with prevention strategies for at-risk patients. Rare manifestations include retinitis and encephalitis. CMV also has an immunosuppressive effect, which can lead to an increased susceptibility to invasive bacterial and fungal disease as well as graftversus-host disease (GvHD). [1]

Cryptic transmission of SARS-CoV-2 in Washington state.

Abstract: After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.

Cryptic transmission of SARS-CoV-2 in Washington State.

Abstract: Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

Animal Models of Depression: What Can They Teach Us about the Human Disease?

Abstract: Depression is apparently the most common psychiatric disease among the mood disorders affecting about 10% of the adult population. The etiology and pathogenesis of depression are still poorly understood. Hence, as for most human diseases, animal models can help us understand the pathogenesis of depression and, more importantly, may facilitate the search for therapy. In this review we first describe the more common tests used for the evaluation of depressive-like symptoms in rodents. Then we describe different models of depression and discuss their strengths and weaknesses. These models can be divided into several categories: genetic models, models induced by mental acute and chronic stressful situations caused by environmental manipulations (i.e., learned helplessness in rats/mice), models induced by changes in brain neuro-transmitters or by specific brain injuries and models induced by pharmacological tools. In spite of the fact that none of the models completely resembles human depression, most animal models are relevant since they mimic many of the features observed in the human situation and may serve as a powerful tool for the study of the etiology, pathogenesis and treatment of depression, especially since only few patients respond to acute treatment. Relevance increases by the fact that human depression also has different facets and many possible etiologies and therapies.