Summary: Purpose:To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy.Methods: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies.Results: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2-4.71. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring of mothers using >1,000 mg VPNday were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed G600 mg VPNday (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found between the offspring exposed to 601-1,000 mg/day and G600 mg/day.Conclusions: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.

It may be concluded that peripheral nerve injuries at the forearm level can result in substantial functional loss and have major social consequences. This study identified factors influencing return to work that can be used to optimize postoperative treatment strategy.

To assess the risk of major congenital abnormalities associated with specific antiepileptic drug regimens, a large retrospective cohort study was performed. The study comprised 1,411 children born between 1972 and 1992 in four provinces in the Netherlands who were born to mothers with epilepsy and using antiepileptic drugs during the first trimester of pregnancy, and 2,000 nonepileptic matched controls. We found significantly increased risks of major congenital abnormalities for carbamazepine and valproate monotherapy, with evidence for a significant dose–response relationship for valproate. The risk of major congenital abnormalities was nonsignificantly increased for phenobarbital monotherapy when caffeine comedication was excluded, but a significant increase in risk was found when caffeine was included. Phenytoin monotherapy was not associated with an increased risk of major congenital abnormalities. Regarding polytherapy regimens, increased risks were found for several antiepileptic drug combinations. Clonazepam, in combination with other antiepileptic drugs, showed a significantly increased relative risk. Furthermore, there were significantly increased relative risks for the combination of carbamazepine and valproate and the combination of phenobarbital and caffeine with other antiepileptic drugs. This study shows that most antiepileptic drug regimens were associated with an increased risk of major congenital abnormalities in the offspring, in particular valproate (dose–response relationship) and carbamazepine monotherapy, benzodiazepines in polytherapy, and caffeine comedication in combinations with phenobarbital.

Forearm and wrist injuries can result in a nonfunctional hand caused by loss of motor and sensory functions. Psychological stress is known to accompany traumatic hand injuries and may therefore affect functional outcome. The authors conducted a retrospective study of 107 patients diagnosed with a median, ulnar, or combined median-ulnar nerve injury (79% response rate) who completed a questionnaire package consisting of the Impact of Event Scale (IES); Disabilities of Arm, Shoulder, and Hand; and a questionnaire concerning return to work and time off work. In an outpatient setting, motor and sensory recovery were examined. Ninety-four percent of those studied experienced early psychological stress. Thirty-six percent of patients reported sufficient symptoms 1 month postoperatively to be classified as in need for psychological treatment (IES score > 30 points). Combined median-ulnar nerve injuries (mean, 35.0 +/- 20.3 points [standard deviation]) were accompanied by a higher psychological stress compared with single nerve injuries (median injuries: mean, 24.2 +/- 20.6 points; ulnar injuries: mean, 22.6 +/- 19.5 points; p = 0.049 and p = 0.021 respectively). Multiple linear regression adjusting for age, gender, and severity of the trauma revealed an association between the IES score and the functional symptom score (beta = 0.51; 95% confidence interval [CI], 0.35-0.65), mean time off work (beta = 0.44; 95% CI, 0.25-0.75), and motor recovery (grip: beta = 0.37; 95% CI, 0.09-0.65; tip-pinch: beta = 0.46; 95% CI, 0.13-0.80). Patients with higher scores on the IES were found to be at increased risk for incapacity for work (odds ratio, 3.32; 95% CI, 1.60-6.91). Higher education was found to be a protecting variable for posttraumatic psychopathology (beta = -0.23; 95% CI, -6.05--0.246). This study demonstrated a high level of early posttraumatic psychological stress after forearm and wrist nerve injuries. These data provide evidence that functional outcome and work resumption are influenced negatively by early psychological stress, independent from severity of the somatic trauma. This indicates that outcome after upper extremity nerve injuries may be influenced positively by psychological intervention.

We have been working on several control and actuation improvements applicable to the design of biomimetic robots and assistive (e.g. prosthetic or orthotic) devices. This paper focuses on the implementation of a jointlevel impedance controller for series-elastic actuators that eliminates the use of joint angle sensor information, instead using information from co-located commutation sensors on the back of a brushless motor and a compression sensor on the series elasticity. This approach is both more robust than previous systems and less subject to instabilities due to stiction and backlash.