A population pharmacokinetic model for escitalopram and its major metabolite in depressive patients during the perinatal period: Prediction of infant drug exposure through breast milk.

BACKGROUND AND OBJECTIVES: Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model that aimed to better characterize maternal and infant exposure to SCIT and its metabolite was developed. METHODS: The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI-Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S-desmethylcitalopram (SDCIT) in plasma using NONMEM and the milk-to-plasma ratio (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation. RESULTS: The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 mL). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight-adjusted maternal SCIT dose on average. CONCLUSION: The moderate between-subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.

Vaginal Neoplasia Induced by an Unusual Papillomavirus Subtype in a Woman with Inherited Chromosomally Integrated Human Herpesvirus Type 6A.

We describe here a case of high-grade vaginal squamous lesion in a 54-year-old woman with a papillomaviruses (HPV) genital infection that developed from a cervical low-grade squamous intraepithelial lesion (SIL) to a high-grade SIL (H-SIL) on cytological examination. A colposcopy exam led to the detection of suspect vaginal lesions with granulomatous infiltrations, which were classified as a Vaginal Intra-Epithelial Neoplasia grade 2 after pathologists' analyses. After a laser vaginal surgery and a loop excision of the transformation zone, the analyses of the anatomical pieces using a near-complete HPV screening panel revealed an HPV-4 infection that was not detected before in cervical smears. This HPV-infection is associated with a high human herpesvirus type 6A (HHV-6A) viral load in the same anatomical piece. The presence of an inherited chromosomally integrated HHV-6A (iciHHV-6A) was proved in this patient by real-time polymerase chain reaction on hair follicles and nail. This case suggests reconsidering both the benign nature of low-grade lesions in the female genital tract and the well-known "good" prognosis of low-risk HPV infection, especially when iciHHV-6A is diagnosed. This clinical course insists on the benefits of the multiplex panel use or global sequencing in order to optimize biological testing sensitivity, and so enhance clinical management of infection-induced neoplasia.

Early pelvic floor muscle training after obstetrical anal sphincter injuries for the reduction of anal incontinence.

OBJECTIVES: Between 0.5 and 5% of vaginal deliveries involve obstetrical anal sphincter injuries (OASIS). Thirty to forty percent of patients with OASIS will suffer from anal incontinence in the subacute postpartum period. The aim of the present study was to assess the effectiveness of early pelvic floor muscle training (PFMT) combined with standard rehabilitation on anal incontinence after vaginal deliveries complicated by OASIS. STUDY DESIGN: The present work was a retrospective quantitative study performed in a tertiary-level maternity hospital. Women with 3rd or 4th degree obstetric tears were included. Women who gave birth between January 1st, 2011 and December 31st, 2012 underwent standard pelvic-perineal rehabilitation within 6-8 weeks postpartum. Women who gave birth between January 1st, 2013 and July 1st, 2014 had early rehabilitation (within 30 days after delivery) followed by the same standard rehabilitation received by the other group. Rehabilitation was performed by physiotherapists specialized in perineology. No electrostimulation was done in early rehabilitation. An in-house-validated modification of the Jorge and Wexner questionnaire was sent by mail to the patients to assess symptoms. The main judgment criterion was anal incontinence to gas, loose stools and/or solid stool. RESULTS: Two hundred and thirty patients were diagnosed with OASIS. Nineteen women (8.3%) were lost to follow-up. The intention-to-treat analysis included 211 patients, 109 of whom underwent standard rehabilitation and 102 early rehabilitation plus standard rehabilitation. The two groups were comparable in terms of parity, birth weight, assisted delivery, epidural anesthesia and rates of mediolateral episiotomy. Multivariate analyses adjusted for type of perineal lesion were performed. Early rehabilitation significantly reduced gas leakage: OR 0.51 [0.29-0.90] (p=0.02), liquid stool leakage: OR 0.22 [0.08-0.58] (p=0.02) and urinary stress incontinence: OR 0.43 [0.24-0.77] (p=0.004). CONCLUSIONS: We recommend early (during the first month postpartum) PFMT after vaginal deliveries associated with OASIS. Rehabilitation should be carried out by a physiotherapist specialized in perineology in order to prevent medium-term functional consequences. A longer follow-up may be necessary to confirm the stability of results.