Cardiovascular disease morbidity has increased worldwide. Organs‐on‐chips and human pluripotent stem cell (hPSC) technologies aid to overcome some of the limitations in cardiac in vitro models. Here, a bi‐compartmental, monolithic heart‐on‐chip device that facilitates porous membrane integration in a single fabrication step is presented. Moreover, the device includes open‐top compartments that allow facile co‐culture of hPSC‐derived cardiomyocytes and human adult cardiac fibroblast into geometrically defined cardiac microtissues. The device can be reversibly closed with a glass seal or a lid with fully customized 3D‐printed pyrolytic carbon electrodes allowing electrical stimulation of cardiac microtissues. A subjacent microfluidic channel allowed localized and dynamic drug administration to the cardiac microtissues, as demonstrated by a chronotropic response to isoprenaline. Moreover, the microfluidic channel can also be populated with human induced pluripotent stem‐derived endothelial cells allowing co‐culture of heterotypic cardiac cells in one device. Overall, this study demonstrates a novel heart‐on‐chip model that systematically integrates an open‐top device with a 3D printed carbon electrode for electrical pacing and culture of cardiac tissues while enabling active perfusion and dynamic drug dosing. Advances in the engineering of human heart‐on‐chip models represent an important step towards making organ‐on‐a‐chip technology a routine aspect of preclinical cardiac drug development.
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. ResultsThe 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.
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