Cost-utility analysis of a structured medication review compared to usual care in Parkinson's disease.

PURPOSE: For controlling symptoms in Parkinson's disease (PD) together with treating additional comorbidities, patients often face complex medication regimens, with suboptimal adherence, drug-related problems, and diminished therapy efficacy as a common consequence. A medication review could potentially tackle these issues, among others by optimizing drug treatment. Even if no change in clinical outcomes is observed, this intervention might decrease health care costs by reducing drug-related problems and hospital admissions. This study aimed to gain more insight in the health benefits and costs of a structured medication review (SMR) in PD. METHODS: A cost-utility analysis was performed, based on a multicenter randomized controlled trial with 202 PD patients with polypharmacy. The intervention group received an SMR, whereas the control group received usual care. The intervention effect after 6 months of follow-up was presented as incremental quality-adjusted life years (QALY) using the EQ-5D-5L questionnaire. Costs were based on real-world data. Missing data was imputed using multiple imputation techniques. Bootstrapping was used to estimate the uncertainty in all health and economic outcomes. RESULTS: The QALY gain in the intervention group compared to the control group was - 0.011 (95% CI - 0.043; 0.020). Incremental costs were €433 (95% CI - 873; 1687). When adapting a willingness-to-pay threshold of €20,000/QALY and €80,000/QALY, the probability of SMRs being cost-effective was 18% and 30%, respectively. CONCLUSION: A community pharmacist-led SMR in PD patients in the current setting shows no apparent benefit and is not cost-effective after 6 months, compared to usual care. TRIAL REGISTRATION: Netherlands Trial Register, NL4360. Registered 17 March 2014.

The effect of incorrect prior information on trust behavior in adolescents.

During adolescence, social cognition and the brain undergo major developments. Social interactions become more important, and adolescents must learn that not everyone can be trusted equally. Prior knowledge about the trustworthiness of an interaction partner may affect adolescents' expectations about the partner. However, the expectations based on prior knowledge can turn out to be incorrect, causing the need to respond adaptively during the interaction. In the current fMRI study, we investigated the effect of incorrect prior knowledge on adolescent trust behavior and on the neural processes of trust. Thirty-three adolescents (Mage = 17.2 years, SDage = 0.5 years) played two trust games with partners whose behavior was preprogrammed using an algorithm that modeled trustworthy behavior. Prior to the start of both games, participants received information suggesting that the partner in one game was untrustworthy (raising incorrect expectations) and the partner in the other game trustworthy (raising correct expectations). Results indicated that participants adapted their trust behavior following incorrect prior expectations. No evidence for a change in trust behavior was shown when prior expectations were correct. fMRI analyses revealed that when receiving the partner's response, activity in the dorsolateral prefrontal cortex and in the superior parietal gyrus were increased when participants had incorrect expectations about the partner compared to when participants had correct expectations. When making trust decisions, no significant differences in neural activity were found when comparing the two games. This study provides insight into how adolescent trust behavior and neural mechanisms are affected by expectations and provides an increased understanding of the factors that influence adolescent social interactions.

Catalytic sites for 3' and 5' incision of Escherichia coli nucleotide excision repair are both located in UvrC.

Nucleotide excision repair in Escherichia coli is a multistep process in which DNA damage is removed by incision of the DNA on both sides of the damage, followed by removal of the oligonucleotide containing the lesion. The two incision reactions take place in a complex of damaged DNA with UvrB and UvrC. It has been shown (Lin, J. -J., and Sancar, A. (1992) J. Biol. Chem. 267, 17688-17692) that the catalytic site for incision on the 5' side of the damage is located in the UvrC protein. Here we show that the catalytic site for incision on the 3' side is in this protein as well, because substitution R42A abolishes 3' incision, whereas formation of the UvrBC-DNA complex and the 5' incision reaction are unaffected. Arg(42) is part of a region that is homologous to the catalytic domain of the homing endonuclease I-TevI. We propose that the UvrC protein consists of two functional parts, with the N-terminal half for the 3' incision reaction and the C-terminal half containing all the determinants for the 5' incision reaction.