Objective To study the dispensing of potentially teratogenic drugs in the 12-month period before as well as during pregnancy in the Netherlands.Design Population-based study.Setting A cohort was constructed using a linkage between the PHARMO Database Network and the Netherlands Perinatal Registry (PRN). Mean outcome measures Proportion of pregnancies that received potentially teratogenic drugs in the 12-month period before and during pregnancy and specific for the risk category X drugs and newly initiated drugs.Results Sixteen percent of the pregnancies received a potentially teratogenic drug in the 12-month period before and 5.07% during pregnancy. Doxycycline and paroxetine were most frequently received during pregnancy by 1.01% and 0.85% of women, respectively; 0.66% of the women received a risk category X drug during pregnancy which most frequently consisted of triptorelin (0.25%), norethisterone (0.22%) and simvastatin (0.03%). Fifty-three percent of the women who received a potentially teratogenic drug during pregnancy received this for the first time during the study period. These percentages were heterogeneous between therapeutic drug classes.Conclusions Five percent of the pregnancies received a potentially teratogenic drug during pregnancy and 0.66% received a drug from the risk category X. It may be possible to reduce these proportions when reasons for prescription have been explored.

ObjectiveTo estimate isotretinoin exposure in Dutch pregnant women despite the implemented pregnancy prevention programme (PPP) and second, to analyse the occurrence of adverse fetal or neonatal outcomes in these isotretinoin exposed pregnancies.DesignPopulation-based study.SettingThe Netherlands.ParticipantsA cohort of 203 962 pregnancies with onset between 1 January 1999 and 1 September 2007 consisting of 208 161 fetuses or neonates.Main outcome measuresIsotretinoin exposure in the 30 days before or during pregnancy. Proportions of adverse fetal or neonatal outcomes, defined as intrauterine deaths ≥16 week of gestation and neonates with major congenital anomalies. ORs with 95% CIs adjusted for maternal age were calculated to estimate the risk of adverse fetal or neonatal outcome after maternal isotretinoin exposure.Results51 pregnancies, 2.5 (95% CI 1.9 to 3.3) per 10 000 pregnancies, were exposed to isotretinoin despite the pregnancy prevention programme. Forty-five of these pregnancies, 2.2 (95% CI 1.6 to 2.9) per 10 000 pregnancies, were exposed to isotretinoin during pregnancy and six additional women became pregnant within 30 days after isotretinoin discontinuation. In 60% of isotretinoin exposed pregnancies, women started isotretinoin while already pregnant. In five out of the 51 isotretinoin exposed pregnancies (53 fetuses), 9.4% (95% CI 1.3% to 17.6%), had an adverse fetal or neonatal outcome. The OR for adverse fetal or neonatal outcomes after isotretinoin exposure in 30 days before or during pregnancy was 2.3 (95% CI 0.9 to 5.7) after adjustment for maternal age.ConclusionsAlthough a PPP was already implemented in 1988, we showed that isotretinoin exposed pregnancies and adverse fetal and neonatal events potentially related to the exposure still occur. These findings from the Netherlands add to the evidence that there is no full compliance to the isotretinoin PPP in many Western countries. Given the limited success of iPLEDGE, the question is which further measures are able to improve compliance.

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Few data have been published on healthcare resource utilisation associated with chemotherapy-induced febrile neutropenia (FN) in Europe. Using the PHARMO record linkage system, we identified incident adult patients with a primary hospital discharge diagnosis of breast cancer (BC) or non-Hodgkin lymphoma (NHL) from 1998 to 2008. Patients who experienced FN were matched 1:2 non-FN reference patients. Of 1033 BC patients, 80 (8%) had FN and were matched with 160 reference patients; and of 486 NHL patients, 95 (20%) had FN and 89 were matched with 178 reference patients. Significantly more FN patients were hospitalised for any cause than reference patients: BC, 81% vs. 24% (OR 12.6; 95% CI 5.7-27.8); NHL, 82% vs. 44% (OR 6.7; 95% CI 3.3-13.9). Median length of all-cause hospitalisation stay was higher for FN patients: BC, 4.0 vs. 1.0 days; NHL, 8.5 vs. 1.8 days. The median (interquartile range) number of medication treatments was higher for FN patients: BC, 5.5 (4.0-7.5) vs. 2.0 (2.0-4.0); NHL, 8.0 (5.0-11.0) vs. 3.0 (2.0-4.0). In conclusion, FN in patients with BC or NHL had increased healthcare utilisation compared with non-FN patients; thus, efforts to reduce FN are warranted to reduce cost and improve outcomes.

Background: In randomized controlled trials, patients with type 2 diabetes mellitus required higher doses of insulin detemir than insulin glargine to obtain the same glycemic control. However, this may differ in daily clinical practice. Methods: We conducted a cohort study to compare glycemic control, daily basal insulin dose and persistence in The Netherlands. Data were obtained from the PHARMO record linkage system. Patients starting glargine or detemir in 2004 through 2007 were included if they had a follow-up and history of at least 1 year, including glycated hemoglobin (HbA 1c) measurements. Glycemic control and insulin dose were compared within 1 year after start of treatment. Average insulin dose was calculated based on the amount of insulin dispensed over time. Results: A total of 708 patients on glargine and 298 on detemir were included. Patients starting glargine had less often used insulin in the previous year (19 versus 31%, P<0.001) and less often used oral antihyperglycemic drugs concomitantly (61 versus 67%, P<0.05) than those starting detemir. Despite a higher mean HbA 1c at baseline in patients who started glargine (8.6% versus 8.4%), the change from baseline in HbA 1c at follow-up was greater with glargine (-0.9%) than with detemir (-0.4%, P<0.001). The proportion of patients with HbA 1c < 7% was similar between the two cohorts. Mean insulin dose at follow-up was significantly lower with glargine than with detemir (31.3 IU versus 36.6 IU, P<0.01). Conclusions: Patients with type 2 diabetes mellitus who were treated with insulin glargine achieved better glycemic control with lower insulin doses than did patients who were treated with insulin detemir. J ou rna l o f D ia be tes & M e ta bolism