Persistence of Antipsychotic Use After Clozapine Discontinuation:A Real-World Study Across Antipsychotics

Although clozapine treatment is often discontinued due to limited efficacy or low tolerability, there is a lack of guidelines and evidence on treatment options after discontinuation of clozapine in patients with schizophrenia. Persistence has proven to be an adequate indicator for treatment effectiveness in patients with schizophrenia. The aim of this study was, therefore, to compare persistence of antipsychotic use between antipsychotic treatment options in patients after stopping clozapine treatment. Registry data from a prescription database representative of the Dutch population (1996-2017) was collected to investigate persistence in patients with schizophrenia who had been using clozapine for >= 90 days. Persistence with antipsychotics after clozapine discontinuation was analyzed using Cox-proportional hazard regression models. Our study population consisted of 321 participants, of whom 138 re-initiated clozapine and 183 started some other antipsychotic in the year after clozapine discontinuation (N = 518 antipsychotic use periods, N = 9,178 months). Second-generation antipsychotics (SGAs) as a group were associated with better persistence compared to first-generation antipsychotics (adjusted hazard ratio (aHR), 0.73; 95% confidence interval (CI) 0.57-0.93; P = 0.011). Compared with other antipsychotics, the following oral monotherapy antipsychotics were associated with significantly better persistence: restarting clozapine (aHR 0.48; 95% CI 0.32-0.71; P <0.001) and switching to risperidone (aHR 0.52; 95% CI 0.32-0.84; P = 0.008) or olanzapine (aHR 0.55; 95% CI 0.35-0.87; P = 0.010). Sensitivity analyses confirmed the results. In conclusion, oral SGAs are associated with better persistence than alternative antipsychotic treatment options in patients discontinuing clozapine for undefined reasons. Especially clozapine (except in those with previous serious adverse reactions to clozapine), olanzapine and risperidone should be considered as oral monotherapy for these patients

Trends in psychostimulant drug use among adults in the Netherlands

Background Use of psychostimulants among children and adolescents receives a lot of attention. However, less is known about the use of these drugs among adults. The aim of our study was to describe trends in the use of psychostimulants among adults over time. Methods Data on adults (≥ 18 years), receiving two or more prescriptions for a psychostimulant drug (ATC-code N06BA; excluding modafanil) within 12 months, were selected from the IADB, a Dutch database of filled prescriptions (59 public pharmacies, about 600.000 patients). We calculated both the number of new users as well as the total number of users of psychostimulants in 2004-2014. Furthermore, we determined the most commonly prescribed psychostimulant drug and whether the psychostimulant was initiated by GP or medical specialist. Results The proportion of psychostimulants users (methylphenidate, dexamphetamine and amphetamine) increased from 1,5 per 1000 adults in 2004 to 7,8 per 1000 adults in 2014. Users were mainly male (63,0%) and methylphenidate predominated (85,7%). The proportion of new users of these drugs increased from 0,5 to 1,5 per 1000 adults. The largest increase was observed among young adults (< 30 year). Since 2012, the increase in new users seems to stabilize. Around 40% of new treatments were initiated by GPs. Conclusion The large increase in use of psychostimulants seems mainly due to an increase in the proportion of new users, especially among young adults. As psychostimulants are only approved for the treatment of ADHD among children (>6 years) and adolescents, short and long term effects and side effects of these drugs need to be assessed in the adult population

Knowledge and attitude regarding pharmacogenetics among formerly pregnant women in the Netherlands and their interest in pharmacogenetic research

BACKGROUND: Pharmacogenetics is an emerging field currently being implemented to improve safety when prescribing drugs. While many women who take drugs during pregnancy would likely benefit from such personalized drug therapy, data is lacking on the awareness towards pharmacogenetics among women. We aim to determine the level of knowledge and acceptance of formerly pregnant women in the Netherlands regarding pharmacogenetics and its implementation, and their interest in pharmacogenetic research. METHODS: A population-based survey using postal questionnaires was conducted among formerly pregnant women in the Northern parts of the Netherlands. A total of 986 women were invited to participate. RESULTS: Of the 219 women who returned completed questionnaires (22.2% response rate), only 22.8% had heard of pharmacogenetics, although the majority understood the concept (64.8%). Women who had experience with drug side-effects were more likely to know about pharmacogenetics [OR = 2.06, 95% CI 1.16, 3.65]. Of the respondents, 53.9% were positive towards implementing pharmacogenetics in their future drug therapy, while 46.6% would be willing to participate in pharmacogenetic research. Among those who were either not willing or undecided in this regard, their concerns were about the consequences of the pharmacogenetic test, including the privacy and anonymity of their genetic information. CONCLUSION: The knowledge and attitude regarding the concept of pharmacogenetics among our population of interest is good. Also, their interest in pharmacogenetic research provides opportunities for future research related to drug use during pregnancy and fetal outcome

Cross-border comparison of antibiotic prescriptions among children and adolescents between the north of the Netherlands and the north-west of Germany

Abstract Background Antibiotic resistance is a worldwide problem and inappropriate prescriptions are a cause. Especially among children, prescriptions tend to be high. It is unclear how they differ in bordering regions. This study therefore examined the antibiotic prescription prevalence among children in primary care between northern Netherlands and north-west of Germany. Methods Two datasets were used: The Dutch (IADB) comprises representative data of pharmacists in North Netherland and the German (BARMER GEK) includes nationwide health insurance data. Both were filtered using postal codes to define two comparable bordering regions with patients under 18 years for 2010. Results The proportion of primary care patients receiving at least one antibiotic was lower in northern Netherlands (29.8 %; 95 % confidence interval [95 % CI]: 29.3–30.3), compared to north-west Germany (38.9 %; 95 % CI: 38.2–39.6). Within the respective countries, there were variations ranging from 27.0 to 44.1 % between different areas. Most profound was the difference in second-generation cephalosporins: for German children 25 % of the total prescriptions, while for Dutch children it was less than 0.1 %. Conclusions This study is the first to compare outpatient antibiotic prescriptions among children in primary care practices in bordering regions of two countries. Large differences were seen within and between the countries, with overall higher prescription prevalence in Germany. Considering increasing cross-border healthcare, these comparisons are highly valuable and help act upon antibiotic resistance in the first line of care in an international approach

Laws on Robots, Laws by Robots, Laws in Robots:Regulating Robot Behaviour by Design

Speculation about robot morality is almost as old as the concept of a robot itself. Asimov’s three laws of robotics provide an early and well-discussed example of moral rules robots should observe. Despite the widespread influence of the three laws of robotics and their role in shaping visions of future robo-dense worlds, these laws have been neglected as futuristic by hands-on roboticists who have been busy with addressing less abstract questions about robots’ behaviour concerning space locomotion, obstacles avoidance, automatic learning, among others. Between morality and function lies a vast gap. When robots enter our everyday lives they will have to observe social and legal norms. For example, social robots in the hospitals are expected to observe social rules (they should not interrupt a mourning family) and robotic dust cleaners scouring the streets for waste as well as automated cars will have to observe traffic regulation. In this article we elaborate on the various ways in which robotic behaviour is regulated. We distinguish between imposing regulations on robots, imposing regulation by robots, and imposing regulation in robots. In doing this, we distinguish regulation that aims at influencing human behaviour and regulation whose scope is robots’ behaviour. We claim that the artificial agency of robots requires designers and regulators to look at the question of how to regulate robots’ behaviour in a way that renders it compliant with legal norms. Regulation by design offers a means for this. We further explore this idea through the example of automated cars