This report provides direct evidence of the transfer of dabigatran and its prodrug across the term human placenta from the mother to the fetus. From a clinical perspective, these data suggest that, pending further study, dabigatran should not be used for anticoagulation of pregnant women, because the drug may have an adverse effect on fetal blood coagulation.

Because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is critical for women of childbearing age to continue folate supplementation during oral contraceptive use.

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Abstract:Objective:One the greatest challenges of BoNT A therapy for tremor lies in the complexity and variation of components involved in tremor movement, and the lack of objective measures to determine these components. This 3 month open-label single injection study aims to couple clinician best judgment with kinematics to improve effect of BoNT A (incobotulinumtoxinA) injection in 7 patients with upper limb Parkinson's disease (PD) tremor.Methods:Injection was guided with clinical and kinematic assessment of tremor using angular wrist position in 3 degrees of freedom: flexion/extension, pronation/supination, and radial/ulnar deviation. Overall tremor severity and change were measured by linear finger acceleration.Results:Kinematic data from static and functional tasks demonstrate no improvement at one month post-injection, but significant improvement at two and three months. Clinical scales across UPDRS Items 20 (1, 2, 3 months post) and 21 (2 months), and spiral drawings (3 months) showed significant improvement from baseline, while line drawings did not.Conclusions:This study suggests injection of BoNT A as a viable focal management option for upper limb PD tremor. In addition to clinical judgment, objective quantification of tremor dynamics by kinematics may be a feasible assessment and guidance tool which can be used to optimize injection conditions for focal tremor therapy. Kinematic analysis of tremor across a variety of joints in all degrees of movement may provide important insight into tremor dynamics, allowing optimized, targeted focal therapy.

Background: Treatment options for essential (ET) and Parkinson disease (PD) tremor are suboptimal, with significant side effects. Botulinum toxin type A (BoNT A) is successfully used in management of various focal movement disorders but is not widely used for tremor. Method: This study examines complexity of wrist tremor in terms of involvement of its three anatomical degrees of freedom (DOF) in two common situations of rest and posture. The study examines tremor in 11 ET and 17 PD participants by kinematic decomposition of motion in 3-DOF. Results: Tremor decomposition showed the motion involved more than one DOF (<70% contribution in one DOF) in most ET (rest: 100%, posture: 64%) and PD (rest: 77%, posture: 77%) patients. Task variation resulted in change in both amplitude and composition in ET, but not in PD. Amplitude significantly increased from rest to posture in ET. Directional bias was observed at the wrist for ET (pronation), and PD (extension, ulnar deviation, pronation). Average agreement between clinical visual and kinematic selection of muscles was 55% across all subjects. Conclusion: This study shows the complexity of tremor and the difficulty in visual judgment of tremor, which may be key to the success of targeted focal treatments such as BoNT A.RÉSUMÉ: Décomposition dynamique du mouvement dans le tremblement essential et le tremblement parkinsonien. Contexte : Les options de traitement du tremblement essentiel (TE) et du tremblement dû à la maladie de Parkinson (MP) sont sous-optimales et comportent des effets secondaires importants. La toxine botulique de type A (BoNT A) est utilisée avec succès dans le traitement de différents troubles focaux du mouvement, mais elle n'est pas utilisée couramment pour traiter le tremblement. Méthode : Cette étude examine la complexité du tremblement du poignet en termes de ses trois degrés anatomiques de liberté (DDL) dans deux situations fréquentes soit le tremblement de repos et le tremblement postural. L'étude examine le tremblement chez 11 patients atteints de TE et 17 patients atteints de MP au moyen de la décomposition cinématique du mouvement en 3 DDL. Résultats: La décomposition du tremblement a montré que le mouvement impliquait plus d'un DDL (contribution <70% dans un DDL) chez la plupart des patients atteints de TE (de repos : 100% ; postural : 64%) et chez les patients atteints de MP (de repos : 77% ; postural : 77%). Une variation des tâches provoquait un changement tant de l'amplitude que de la composition dans le TE, mais non dans la MP. L'amplitude augmentait significativement du repos à la situation du maintien d'une posture dans le TE. Un biais directionnel a été observé au niveau du poignet dans le TE (pronation) et dans la MP (extension, déviation cubitale, pronation). La concordance moyenne entre la sélection visuelle clinique et cinématique des muscles était de 55% pour l'ensemble des sujets. Conclusion : Cette étude montre la complexité du tremblement et la difficulté de porter un jugement visuel sur le tremblement, un élément c...

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Varicella infection during pregnancy is associated with serious maternal and fetal complications such as congenital varicella syndrome, maternal pneumonia and neonatal varicella. Pregnant women are ineligible to receive the varicella vaccination, thus women who lack evidence of immunity to varicella are at an increased risk for developing a varicella infection if exposed to a contagious individual. Presently, post-exposure prophylaxis involves the administration of a varicella zoster immunoglobulin (VariZIG™) to prevent or reduce the severity of an infection. The US FDA recently approved VariZIG for licensure and recommend that it be administered as soon as possible following VZV exposure, ideally within 96 h for greatest effectiveness. The following review critically examines the role of VariZIG in post-exposure prophylaxis of varicella during pregnancy.

• Apixaban is a novel oral anticoagulant that has not been studied in pregnant patients.• Our objective was to determine the rate and extent of the placental transfer of apixaban.• Apixaban rapidly crosses the ex vivo term human placenta from maternal to fetal circulation.• Fetal apixaban levels in vivo are estimated to be 35-90% of the corresponding maternal levels.Summary. Background: Apixaban is a novel oral anticoagulant that is increasingly being prescribed to women of reproductive age. However, information regarding its placental transfer is non-existent. Objective: To determine the rate and extent of placental transfer of apixaban, using the human placenta ex vivo. Methods: Placentae collected after Caesarean or vaginal delivery of healthy term infants were perfused in the respective maternal and fetal circulation. At the start of the experiment, apixaban was added to the maternal circulation at a concentration of 150 ng mL À1 , and samples from maternal and fetal reservoirs were collected over 3 h. Results: There was a rapid decline of apixaban in the maternal compartment, followed by emergence in the fetal compartment with a median fetal-to-maternal drug concentration ratio of 0.77 (interquartile range [IQR], 0.76-0.81) and fetal concentration of 39.0 ng mL À1 (IQR, 36.8-40.6) after 3 h (n = 5).The perfusion results were subsequently adjusted to account for differences in the concentration of plasma proteins in maternal and fetal blood, as apixaban remains highly bound to albumin and alpha-1 acid glycoprotein. After the adjustment, the predicted fetal-to-maternal ratio of total (bound plus unbound) apixaban concentrations in vivo ranged from 0.35 to 0.90. Conclusions: We conclude that unbound apixaban rapidly crosses from the maternal to fetal circulation. We further predict that total apixaban concentrations in cord blood in vivo are 35-90% of the corresponding maternal levels, suggesting that apixaban could have a possible adverse effect on fetal and neonatal coagulation.