Physiologically-based pharmacokinetic model to investigate the effect of pregnancy on risperidone and paliperidone pharmacokinetics: Application to a pregnant woman and her neonate.

This study aimed to determine the effects of pregnancy and ontogeny on risperidone and paliperidone pharmacokinetics by assessing their serum concentrations in two subjects and constructing a customized physiologically-based pharmacokinetic (PBPK) model. Risperidone and paliperidone serum concentrations were determined in a pregnant woman and her newborn. PBPK models for risperidone and paliperidone in adults, pediatric, and pregnant populations were developed and verified using the Simcyp simulator. These models were then applied to our two subjects, generating their "virtual twins." Effects of pregnancy on both drugs were examined using models with fixed pharmacokinetic parameters. In the neonatal PBPK simulation, 10 different models for estimating the renal function of neonates were evaluated. Risperidone was not detected in the serum of both pregnant woman and her newborn. Maternal and neonatal serum paliperidone concentrations were between 2.05-3.80 and 0.82-1.03 ng/ml, respectively. Developed PBPK models accurately predicted paliperidone's pharmacokinetics, as shown by minimal bias and acceptable precision across populations. The individualized maternal model predicted all observed paliperidone concentrations within the 90% prediction interval. Fixed-parameter simulations showed that CYP2D6 activity largely affects risperidone and paliperidone pharmacokinetics during pregnancy. The Flanders metadata equation showed the lowest absolute bias (mean error: 22.3% ± 6.0%) and the greatest precision (root mean square error: 23.8%) in predicting paliperidone plasma concentration in the neonatal population. Our constructed PBPK model can predict risperidone and paliperidone pharmacokinetics in pregnant and neonatal populations, which could help with precision dosing using the PBPK model-informed approach in special populations.

Correction to: Review of the efforts of the Japanese Society of Echocardiography for coronavirus disease 2019 (COVID-19) during the initial outbreak in Japan.

In the original publication of the article, the text citations of the Figs. 4-1, 4-2 and 5 should be Figs. 4, 5 and 6.

Review of the efforts of the Japanese Society of Echocardiography for coronavirus disease 2019 (COVID-19) during the initial outbreak in Japan.

Under the coronavirus disease 2019 (COVID-19) pandemic, the Japanese Society of Echocardiography (JSE) has been working to protect medical staff involved in echocardiographic examinations and to prevent secondary infections caused by the examinations since mid-March 2020. This review aims to describe the footprint of the JSE's responses, focusing on the 3 months in which the initial outbreak of COVID-19 pandemic occurred in Japan. We summarized the six parts as follows: (1) the initial actions for COVID-19 of JSE, (2) JSE's actions for infection control-associated echocardiographic examinations, (3) statements from the American Society of Echocardiography during the COVID-19 pandemic and their Japanese translation by JSE, (4) making videos for explaining the practice of echocardiography during the COVID-19 pandemic, (5) attempts with the JSE members' opinions by the communication platform and surveys, and (6) efforts of final statement during the initial spread of COVID-19. We look forward that this review will help daily practices associated with echocardiography under the COVID-19 pandemic and in the future event of an unknown infectious disease pandemic.

Effect of the COVID-19 Pandemic on Acute Respiratory Care of Hypoxemic Patients With Acute Heart Failure in Japan　- A Cross-Sectional Study.

Background: The effect of the COVID-19 pandemic on the respiratory management strategy with regard to the use of non-invasive positive pressure ventilation (NPPV) and high-flow nasal cannula (HFNC) in patients with acute heart failure (AHF) in Japan is unclear. Methods and Results: This cross-sectional study used a self-reported online questionnaire, with responses from 174 institutions across Japan. More than 60% of institutions responded that the treatment of AHF patients requiring respiratory management became fairly or very difficult during the COVID-19 pandemic than earlier, with institutions in alert areas considering such treatment significantly more difficult than those in non-alert areas (P=0.004). Overall, 61.7% and 58.8% of institutions changed their indications for NPPV and HFNC, respectively. Significantly more institutions in the alert area changed their practices for the use of NPPV and HFNC during the COVID-19 pandemic (P=0.004 and P=0.002, respectively). When there was insufficient time or information to determine whether AHF patients may have concomitant COVID-19, institutions in alert areas were significantly more likely to refrain from using NPPV and HFNC than institutions in non-alert areas. Conclusions: The COVID-19 pandemic has compelled healthcare providers to change the respiratory management of AHF, especially in alert areas.