[Switching to a generic drugA blessing or a curse?]. / Overstappen op een generiek geneesmiddel.

A patient suffering from Zollinger-Ellison was treated with Nexium, but after patent expiry only the costs of generic omeprazol were reimbursed. Generic tablets and capsules, pantoprazol and rabeprazol, were tried without success and finally the pharmacist dispensed Nexium at his own expense. Registered generic drugs have been shown to be bioequivalent with the originator drug within narrow margins. When two batches of the originator are compared, the same requirements are valid. Although the subject has received a lot of negative publicity, meta-analyses on outcome comparison support generic substitution; problems associated with switching can be partially explained by the loss of trust in the treatment, and differences in appearance also cause confusion. Generic prescribing should be encouraged to keep medical treatment affordable; however, in order to prevent the problems described it is desirable to keep to the same product as far as possible. Effective education and patient information are essential if switching is to be successful.

Association between antidepressant drug use during pregnancy and child healthcare utilisation.

OBJECTIVE: To evaluate healthcare utilisation by children who were exposed to antidepressant drug use during pregnancy and those whose mothers stopped using antidepressants before pregnancy compared with a control group. DESIGN: Cohort study. Setting Health insurance records in the Netherlands. POPULATION: A total of 38 602 children born between 2000 and 2005. METHODS: Survey of child healthcare utilisation in relation to gestational antidepressant use. MAIN OUTCOME MEASURE: Healthcare utilisation rates during the first year of life, with special emphasis to medical care related to cardiac disease. RESULTS: Children of mothers who used antidepressants during pregnancy showed increased healthcare use during the first year of life, independent of the mother's healthcare use. The relative risk of more than two visits to general practitioners was 1.5 (95% confidence interval, CI: 1.3-1.8) in the continuous antidepressant users group and 1.3 (95% CI: 1.2-1.5) in the group of children whose mothers stopped taking medication. In both study groups there was a trend towards more drug use for infections and inflammation compared with the control group. Children continuously exposed to antidepressants had an increased risk of cardiac interventions such as cardiovascular surgery or heart catheterisation, relative risk of 5.6 (95% CI: 1.8-17.4). The risk of physiotherapy was twice as high in the antidepressant group compared with the control group (relative risk 2.0; 95% CI: 1.5-2.6). CONCLUSION: Antidepressant use during pregnancy is associated with increased child healthcare utilisation and increased risk of major cardiac interventions in early childhood.

The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome.

During pregnancy the placental 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) enzyme inactivates prednisolone by interconversion into prednisone, protecting the fetus from high levels of prednisolone. Recent reports suggest decreased placental 11beta-HSD2 activity in pregnancies complicated by preeclampsia. The purpose of our investigation was to study the transplacental passage of prednisolone in patients suffering from early preterm HELLP syndrome, a severe complication of preeclampsia. We examined the maternal and umbilical cord plasma concentration of prednisolone in nine women receiving 50 mg of prednisolone twice a day. Samples were obtained during caesarean section at a gestational age between 27 and 31 weeks. Mean fetal concentration was 10-fold lower as compared to maternal prednisolone concentration (mean+/-SD 52.8 nmol/L+/-27.0 vs. 477.5 nmol/L+/-300, p<0.01). A significant correlation was found between the last dose of prednisolone to delivery interval and the fetal prednisone concentration (Spearman's correlation coefficient r=-0.946, p<0.000). Our data demonstrate unimpaired placental 11beta-HSD2 activity in patients suffering from HELLP syndrome at early gestational age as shown by both a 10-fold lower fetal prednisolone concentration as compared to the mother and a strong correlation between the last dose of prednisolone to delivery interval and the fetal prednisone concentration. Prednisolone may therefore have less effect on the fetus than betamethasone or dexamethasone.

Corticosteroids, pregnancy, and HELLP syndrome: a review.

Corticosteroids are potent antiinflammatory and immunosuppressive drugs, which are used in the treatment of a wide range of medical disorders. During pregnancy, several corticosteroids are administered for maternal as well as fetal reasons. Prednisone and prednisolone show limited transplacental passage and are thus used for treatment of maternal disease. Dexamethasone and betamethasone, drugs that can easily cross the placenta, are more suitable for fetal indications. During the last decade, administration of corticosteroids was introduced in the treatment of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), a severe form of preeclampsia unique to human pregnancy. Several randomized, controlled trials as well as other prospective and retrospective studies have been performed to investigate this beneficial effect of corticosteroids on biochemical measures and clinical signs. This review discusses the characteristics of corticosteroids in humans and details the use of corticosteroids during pregnancy. A review of literature on the effect of corticosteroids on HELLP syndrome is given and possible mechanisms of action are discussed.

Midazolam and amplitude-integrated EEG in asphyxiated full-term neonates.

AIM: In the present, prospective study, the relation between the levels of midazolam, its two active metabolites--1-hydroxy-midazolam (OH-midazolam) and 1-hydroxy-midazolam-glucuronide (glu-midazolam)--and the aEEG were examined. PATIENTS AND METHODS: Fifteen full-term neonates with seizures due to hypoxic-ischaemic encephalopathy admitted to our NICU were included. Midazolam (loading dose 0.05 mg/kg in 10 min, maintenance dose 0.15 mg/kg/h) was used as an add-on anti-convulsant after phenobarbital and lidocaine because of continuing seizures. Amplitude-integrated EEG background pattern was scored at the start of midazolam and at the time of blood sampling as continuous normal voltage (CNV), discontinuous normal voltage (DNV), burst suppression (BS), continuous low voltage (CLV) or flat trace (FT). Serum levels of midazolam, OH-midazolam and glu-midazolam were measured at least 8 h after the start with HPLC. RESULTS: In 11/15 patients, seizures were abolished with the addition of midazolam. In the remaining patients, seizure frequency was reduced in one and unchanged in three. Amplitude-integrated EEG background pattern at the start of midazolam was CNV in two, DNV in six, BS in five and CLV in two. Moderate, temporary suppression of the aEEG background pattern lasting less than 2 h was seen in four neonates. Amplitude-integrated EEG at midazolam sampling was CNV in two, DNV in seven, CLV in two and FT in four. Serum levels of midazolam ranged from 0.10 to 1.76 mg/l, OH-midazolam from 0.05 to 0.28 mg/l and glu-midazolam from 0.85 to 4.36 mg/l. CONCLUSIONS: A brief and moderate suppression of the aEEG background pattern immediately after midazolam was seen in four neonates for less than 2 h. Suppression at a later time point, i.e. after more than 8 h of midazolam infusion, was demonstrated almost exclusively in neonates with a poor background pattern, and therefore these patterns appear to be determined mainly by the severity of hypoxic-ischaemic encephalopathy.