The Experience of Cervical Cancer Patients Undergoing Hysterectomy: A Qualitative Study.

INTRODUCTION: Due to different social and cultural backgrounds, cervical cancer patients' experience of the treatment process and quality of life after treatment will be different. This study sought to gain in-depth understanding of the experiences of Chinese cervical cancer patients as regards their quality of life and physical symptoms. METHODOLOGY: Semi-structured interviews were used to collect data. We recruited 15 women with cervical cancer in eastern China for in-depth interviews. All data were entered into the NVivo 12 software program for analysis. RESULTS: Four themes emerged from the data: (a) uncertainty; (b) physical suffering; (c) psychological pressure; and (d) challenges of marriage and family. DISCUSSION: Cervical cancer patients showed concerns about the disease itself and the physical discomfort it causes, as well as changes in social relations. Health professionals need to talk about these issues and develop strategies to address them accordingly.

Stable Mg Single-Atom Solid Base Catalysts Anchored on Metal-Organic Framework-Derived Nitrogen-Doped Carbon.

Solid base catalysts are widely used in the chemical industry owing to their advantages of environmental friendliness and easy separation. However, their application is limited by basic site aggregation and poor stability. In this study, we report the preparation of magnesium (Mg) single-atom catalysts with high activity and stability by a sublimation-trapping strategy. The Mg net was sublimated as Mg vapor at 620 °C, subsequently transported through argon, and finally trapped on the defects of nitrogen-doped carbon derived from metal-organic framework ZIF-8, producing Mg1/NC. Because of the atomically dispersed Mg sites, the obtained Mg1/NC exhibits high catalytic activity and stability for Knoevenagel condensation of benzaldehyde with malononitrile, which is a typical base-catalyzed reaction. The Mg1/NC catalyst achieves a high efficiency with a turnover frequency of 49.6 h-1, which is much better than that of the traditional counterpart MgO/NC (7.7 h-1). In particular, the activity of Mg1/NC shows no decrease after five catalytic cycles, while that of MgO/NC declines due to the instability of basic sites.

Insights into the population pharmacokinetics and pharmacodynamics of quetiapine: a systematic review.

INTRODUCTION: Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes published population PK/PD studies and identifies significant covariates accounting for this variability to inform precision dosing. METHODS: We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates. RESULTS: Six population PK and three population PK/PD studies were included. The median apparent clearance in adults was 87.7 L/h. Strong and moderate cytochrome P450 3A4 inducers increased the apparent clearance approximately fourfold, while strong cytochrome P450 3A4 inhibitors reduced it by 93%. The half-maximum effect concentrations were 82.8 ng/mL for the Brief Psychiatric Rating Scale and 583 ng/mL for dopamine D2 receptor occupancy. Both treatment duration and quetiapine exposure were associated with weight gain. CONCLUSIONS: Concurrent administration of potent or moderate CYP3A4 inducers and inhibitors need to be avoided in quetiapine-treated patients. When co-medication is required, it is recommended to adjust the dosage based on therapeutic drug monitoring. Additional research is warranted to delineate the dose-exposure-response relationships of quetiapine and active metabolite norquetiapine in pediatrics, geriatrics, hepatically-impaired patients, and women using contraceptives or are pregnant or menopausal. PROSPERO REGISTRATION: CRD42023446654.

Prevalence of psychological problems among caregivers of children and adolescents with neurodevelopmental disorders during the COVID-19 pandemic: A meta-analysis and systematic review.

BACKGROUND: The COVID-19 pandemic impacted children and adolescents with neurodevelopmental disorders, which caused difficulties and increased caregivers' burden. AIM: The objective of this study was to assess the prevalence of psychological problems among caregivers of children and adolescents with neurodevelopmental disorders. Methods and procedures We searched the PubMed, Embase and Web of Science databases for relevant studies published from December 2019 to March 2023. Random effects models were used to calculate the pooled prevalence of psychological problems among caregivers. Subgroup analyses were used to detect potential heterogeneity and sensitivity analyses were performed to evaluate the robustness of the included studies. Egger's and Begg's tests were used to examine publication bias. Outcomes and results Twenty studies involving 14,743 participants were included in this systematic review and meta-analysis. The main psychological problems among caregivers were anxiety (36.6%, 95% confidence interval [CI] 19.6-53.7%), depression (41.1%, 95%CI 35.4-46.8%), and stress (58.9%, 95%CI 45.1-72.7%). There were differences in prevalence by study year, national economic level, continent, and sample size. Conclusions and implications Our study showed that caregivers of children and adolescents with neurodevelopmental disorders had a high prevalence of anxiety, depression, and stress during the COVID-19 pandemic. Therefore, the psychological problems of these caregivers should not be overlooked. We recommend that the government should provide caregivers with more medical and financial assistance. What this paper adds? The current study is the first systematic review and meta-analysis focusing on parents whose children have neurodevelopmental disorders during the COVID-19 pandemic. The results show that the prevalence of psychological problems among caregivers of children with neurodevelopmental disorders is particularly prevalent, which suggests that we should attach importance to the parenting pressure and mental health of this special group.

Photo-Responsive Carbon Capture over Metalloporphyrin-C60 Metal-Organic Frameworks via Charge-Transfer.

Great efforts have been devoted to the study of photo-responsive adsorption, but its current methodology largely depends on the well-defined photochromic units and their photo-driven molecular deformation. Here, a methodology to fabricate nondeforming photo-responsive sorbents is successfully exploited. With C60-fullerene doping in metalloporphyrin metal-organic frameworks (PCN-M, M = Fe, Co, or Ni) and intensively interacting with the metalloporphyrin sites, effective charge-transfer can be achieved over the metalloporphyrin-C60 architectures once excited by the light at 350 to 780 nm. The electron density distribution and the resultant adsorption activity are thus changed by excited states, which are also stable enough to meet the timescale of microscopic adsorption equilibrium. The charge-transfer over Co(II)-porphyrin-C60 is proved to be more efficient than the Fe(II)- and Ni(II)-porphyrin-C60 sites, as well as than all the metalloporphyrin sites, so the CO2 adsorption capacity (CAC; at 0 °C and 1 bar) over the C60-doped PCN-Co can be largely improved from 2.05 mmol g-1 in the darkness to 2.69 mmol g-1 with light, increased by 31%, in contrast to photo-irresponsive CAC over all C60-undoped PCN-M sorbents and only the photo-loss CAC over C60.

Transformation of Type III to Type II Porous Liquids by Tuning Surface Rigidity of Rhodium(II)-Based Metal-Organic Polyhedra for CO2 Cycloaddition.

Porous liquids (PLs), a summation of porous hosts and bulky solvents bestowing permanent cavities, are the prominent emerging materials. Despite great efforts, exploration of porous hosts and bulky solvents is still needed to develop new PL systems. Metal-organic polyhedra (MOPs) with discrete molecular architectures can be considered as porous hosts; however, many of them are insoluble entities. Here we report the transformation of type III PL to type II PLs by tuning the surface rigidity of insoluble MOP, Rh24 L24 , in a bulky ionic liquid (IL). Functionalization of N-donor molecules on Rh-Rh axial sites ensue their solubilization in bulky IL which confer type II PLs. Experimental and theoretical studies reveal the bulkiness of IL as per the cage apertures, and the cause of their dissolution as well. The obtained PLs, capturing more CO2 than neat solvent, have depicted higher catalytic activity for CO2 cycloaddition compared to individual MOPs and IL.

Coumarin-functionalized metal-organic frameworks: adsorbents with photo-responsive active sites for adsorptive desulfurization.

Photo-responsive metal-organic frameworks (PMOFs) have great potential in on-demand controllable adsorption processes under distinct light conditions, which is challenging to realize by conventional adsorbents with static frameworks and properties. Here, we report a new type of adsorbent with photo-responsive active sites for adsorptive desulfurization. Coumarin monomers were incorporated in MIL-101(Cr) to construct the photo-responsive adsorbents by coordinating with unsaturated chromium sites. Trigged by UV light (>310 nm), coumarin monomers undergo dimerization to a cyclobutane structure, which forms a conjugation effect with π electrons on the aromatic ring of the sulfur compound, leading to remarkably increased uptake of 4,6-dimethyldibenzothiophene (4,6-DMDBT). Coumarin dimers can transform back to monomers under irradiation of 254 nm UV light, corresponding to decreased adsorption of 4,6-DMDBT. The change in adsorption amount between PMOF and the coumarin monomers and dimers is up to 62.8%. The present study might open up an avenue for the fabrication of adsorbents with on-demand active sites for various applications.

Photo-Induced Construction and Recovery of Cu+ Sites in Metal-Organic Frameworks.

The adjustment of the valence state of metal ions is crucial for various applications because peculiar activity originates from metal ions with specific valence. Cu+ can interact with molecules possessing unsaturated bonds like CO via π-complexation, while Cu2+ doesn't have such ability. Meanwhile, Cu+ sites are easily oxidized to Cu2+ , leading to the loss of activity. Despite great efforts, the development of a facile method to construct and recover Cu+ sites remains a pronounced challenge. Here, for the first time a facile photo-induced strategy is reported to fabricate Cu+ sites in metal-organic frameworks (MOFs) and recover Cu+ after oxidation. The Cu2+ precursor was loaded on NH2 -MIL-125, a typical visible-light responsive Ti-based MOF. Visible light irradiation triggers the formation of Ti3+ from Ti4+ in framework, which reduces the supported Cu2+ in the absence of any additional reducing agent, thus simplifying the process for Cu+ generation significantly. Due to π-complexation interaction, the presence of Cu+ results in remarkably enhanced CO capture capacity (1.16 mmol g-1 ) compared to NH2 -MIL-125 (0.49 mmol g-1 ). More importantly, Cu+ can be recovered conveniently via re-irradiation when it is oxidized to Cu2+ , and the oxidation-recovery process is reversible.

Enhanced CO Adsorption by Modulating the Electron Density Distribution of Graphite-Copper Porphyrin Sorbents with Light.

The photo-responsive adsorption has emerged as a vibrant area, but its current methodology is limited by the well-defined photochromic units and their molecular deformation driven by photo-stimuli. Herein, a methodology of nondeforming photo-responsiveness is successfully exploited. With the exploiting agent of Cu-TCPP framework assembled on the graphite and strongly interacted with it, the sorbent generates two kinds of adsorption sites, over which the electron density distribution of the graphite layer can be modulated at the c-axis direction, which can further evolve due to photo-stimulated excited states. The excited states are stable enough to meet the timescale of microscopic adsorption equilibrium. Independent of the ultra-low specific surface area of the sorbent (20 m2 g-1 ), the CO adsorption capability can be improved from 0.50 mmol g-1 at the ground state to 1.24 mmol g-1 (0 °C, 1 bar) with the visible light radiation, rather than the photothermal desorption.

Significant predictors for olanzapine pharmacokinetics: a systematic review of population pharmacokinetic studies.

INTRODUCTION: Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have been performed to identify factors contributing to the variability and thus facilitate individualized dosing. This review aims to provide a comprehensive overview of published population pharmacokinetic studies and explore potential covariates. METHODS: We systematically searched PubMed, Web of Science, and EMBASE databases from their inception to 31 December 2022. Information on the study design, characteristics, and final parameter estimates was summarized and compared. Monte Carlo simulations provided visual predictive distributions to compare eligible studies. Forest plots were constructed to explore the effects of covariates on olanzapine pharmacokinetics. RESULTS: A total of 10 population pharmacokinetic and three population pharmacokinetic/pharmacodynamic studies involving infants, children, adolescents, and adults were finally included. The median apparent clearance was 0.253 L/h/kg in adults, 27-43% lower than that of infants and children. Men and smokers increased the apparent clearance of olanzapine by 32% and 34%, respectively. The concentration required to achieve half of the maximum effect for the Positive and Negative Syndrome Scale total score was 24.80 ng/mL, comparable with 22.32 ng/mL for dopamine D2 receptor occupancy. CONCLUSIONS: A higher dosage may be required for men or heavy smokers than for women or nonsmokers to reach the same exposure. Moreover, further population studies are essential to be conducted to clarify the dose-exposure-response relationship of olanzapine. PROSPERO REGISTRATION: CRD42022368637.

SM22α Deletion Contributes to Neurocognitive Impairment in Mice through Modulating Vascular Smooth Muscle Cell Phenotypes.

Considerable evidence now indicates that cognitive impairment is primarily a vascular disorder. The depletion of smooth muscle 22 alpha (SM22α) contributes to vascular smooth muscle cells (VSMCs) switching from contractile to synthetic and proinflammatory phenotypes in the context of inflammation. However, the role of VSMCs in the pathogenesis of cognitive impairment remains undetermined. Herein, we showed a possible link between VSMC phenotypic switching and neurodegenerative diseases via the integration of multi-omics data. SM22α knockout (Sm22α-/-) mice exhibited obvious cognitive impairment and cerebral pathological changes, which were visibly ameliorated by the administration of AAV-SM22α. Finally, we confirmed that SM22α disruption promotes the expression of SRY-related HMG-box gene 10 (Sox10) in VSMCs, thereby aggravating the systemic vascular inflammatory response and ultimately leading to cognitive impairment in the brain. Therefore, this study supports the idea of VSMCs and SM22α as promising therapeutic targets in cognitive impairment to improve memory and cognitive decline.

[Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin].

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Detachable Porous Organic Polymers Responsive to Light and Heat.

Stimuli-responsive porous materials have captured much attention due to the on-demand tunable properties. Most reported stimuli-responsive porous materials are based on molecule isomerism or host-guest interaction, and it is highly desired to develop new types based on different responsive mechanism. Herein, inspired by natural cells which have the ability to fuse and divide induced by external stimulation, we report a new type of stimuli-responsive porous material based on detachment mechanism. A detachable porous organic polymer, namely DT-POP-1, is fabricated from the polymerization of anthracene-containing monomer (AnMon) when irradiated by 365 nm UV light. DT-POP-1 can detach into the monomer AnMon when irradiated with 275 nm UV light or heat. Such polymerization/detachment is reversible. The detachment results in a big difference in porosity and adsorption capacity, making the present detachable porous polymer highly promising in adsorptive separation and drug delivery.

Photomodulation on Active Sites of Adsorbents: Controllable Adsorption Processes with Improved Efficiency.

Adsorption is a widely applied technique in producing high-purity chemicals with advantages of low energy consumption, high selectivity, and mild operating conditions. However, traditional adsorbents have inflexible properties and suffer from the trade-off between selective adsorption and efficient desorption. Recently, the emerging photoresponsive adsorbents have provided new avenues for adsorption techniques. Active sites of photoresponsive adsorbents can be regulated through steric hindrance or tunable adsorbent-adsorbate interactions. Therefore, variation in adsorptive capacity is able to readily achieve through photomodulation, and the corresponding adsorption/desorption cycles are energy-saving. This concept mainly summarizes recent efforts on the fabrication and application of photoresponsive adsorbents with tunable active sites. Also, the future opportunities and critical challenges of photoregulation on adsorptive sites are presented.

Is a Lower Dose of Rivaroxaban Required for Asians? A Systematic Review of a Population Pharmacokinetics and Pharmacodynamics Analysis of Rivaroxaban.

Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required for Asians is still debatable. This review aimed to explore the potential ethnic difference in pharmacokinetic/pharmacodynamic (PK/PD) characteristics between Asians and Caucasians. A systematic search was conducted and twenty-four studies were identified, of which 10 were conducted on Asian adults, 11 on predominantly Caucasian adults, and 3 on Caucasian pediatrics. The apparent clearance (CL/F) of rivaroxaban in Caucasian adults with non-valvular atrial fibrillation (6.45-7.64 L/h) was about 31-43% higher than that in Asians (4.46-5.98 L/h) taking 10~20 mg rivaroxaban every 24 h. Moreover, there was no obvious difference in CL/F among Japanese, Chinese, Thai, and Irani people. Regarding PK/PD relationship, prothrombin time was linked to rivaroxaban concentration in a linear or near-linear manner, and Factor Xa activity was linked with the Emax model. The exposure-response relationship was comparable between Asians and Caucasians. Renal function has a significant influence on CL/F, and no covariate was recognized for exposure-response relationship. In conclusion, a lower dose of rivaroxaban might be required for Asians, and further studies are warranted to verify this ethnic difference to facilitate optimal dosing regimens.

Transition Metal Single Atoms Constructed by Using Inherent Confined Space.

Single-atom catalysts (SACs) show expressively enhanced activity toward diverse reactions due to maximized atomic utilization of metal sites, while their facile, universal, and massive preparation remains a pronounced challenge. Here we report a facile strategy for the preparation of SACs by use of the inherent confined space between the template and silica walls in template-occupied mesoporous silica SBA-15 (TOS). Different transition metal precursors can be introduced into the confined space readily by grinding, and during succeeding calcination single atoms are constructed in the form of M-O-Si (M = Cu, Co, Ni, and Zn). In addition to the generality, the present strategy is easy to scale up and can allow the synthesis of 10 g of SACs in one pot through ball milling. The Cu SAC has been applied for CO2 cycloaddition of epichlorohydrin, and the activity is obviously higher than the counterpart prepared without confined space and various reported Cu-containing catalysts.

Endowing Covalent Organic Frameworks with Photoresponsive Active Sites for Controllable Propylene Adsorption.

Photoresponsive covalent organic frameworks (PCOFs) have emerged as attractive candidates for adsorption, but it is challenging to construct PCOF adsorbents due to structural order loss of covalent organic frameworks (COFs) after introducing photoresponsive motifs and/or tedious steps of postmodification. Here, a facile strategy is developed, by dispersing photoresponsive metal-organic polyhedra (PMOP) into COFs, to endow COFs with photoresponsive adsorption sites. As a proof-of-concept study, a COF with pore size of 4.5 nm and PMOP with suitable molecular size (4.0 and 3.1 nm for trans and cis configuration, respectively) are selected to meet the requirements of proper accommodation space, good guest dispersion, and free isomerization. The structure of COF is well preserved after introducing PMOPs. Interestingly, the obtained photoresponsive host-guest composite (PHGC) adsorbents exhibit photomodulated adsorption capacity on propylene (C3 H6 ) and the change in adsorption capacity can reach up to 43.3% and is stable during multiple cycles. Density functional theory calculations reveal that visible-light irradiation drives the azobenzene motifs in PHGCs to the trans configuration and the adsorption sites are fully open and interact with C3 H6 . UV-light irradiation makes the azobenzene motifs transform to the cis configuration, leading to the shield of the adsorption sites and the consequent release of C3 H6 .

Bioactive Dimeric Diterpenoids from Taiwania cryptomerioides (Hayata) and Their Biological Activities.

Taiwania cryptomerioides Hayata is an endangered relict plant belonging to Taxodiaceae, and it is also an endemic plant to China. The decay-resistant of Taiwania timber can provide highly quality wood for building and furniture. Plenty of regenerative of leaves of T. cryptomerioides also has been used as a resource for the discovery of new dimeric diterpenoids. In a search for structurally diverse dimeric diterpenoids and potent bioactive isolates, ten new heterodimeric diterpenoids, taiwaniadducts K-T (1-4, 6, 8-11, and 14), along with five known ones (5, 7, 12, 13, and 15), were isolated from the leaves of T. cryptomerioides. These new compounds were defined by comprehensive spectroscopic analyses, putative biosynthetic pathways, and the values of optical. Biologically, anti-multidrug resistance (MDR) activities of compounds were evaluated. Compounds 4 and 10 exerted a 9.18-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration (20 µM) better than the positive control verapamil. The research of the leaves of T. cryptomerioides not only added the new data to the structural diversity and activities of dimeric diterpenoids but also could provide support for the medical and industrial application of the leaves of this endangered relict plant.

How to handle a delayed or missed dose of edoxaban in patients with non-valvular atrial fibrillation? A model-informed remedial strategy.

AIMS: Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for the long-term prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOAC therapy has been unsatisfactory and decreases over time. Remedial strategies are currently used to address the non-adherence events. Current recommendations, however, are generic and not well supported by evidence. The aim of this study was to explore appropriate remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through Monte Carlo simulation. METHODS: Six regimens were compared with the current recommendations of the European Heart Rhythm Association (EHRA) guide based on total deviation time. Both edoxaban plasma concentration and intrinsic Factor Xa activity were considered. Monte Carlo simulations were performed using RxODE based on a published population pharmacokinetic/pharmacodynamic (PK/PD) model. RESULTS: The proposed remedial strategies were different than the EHRA recommendations and were related to the delay time. However, it was found that the missed dose can be administered immediately if the delay time is within 11 h. When the delay is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred. CONCLUSION: PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which can help maximise its therapeutic effect.

Handling Delayed or Missed Dose of Antiseizure Medications: A Model-Informed Individual Remedial Dosing.

BACKGROUND AND OBJECTIVES: Delayed or missed antiseizure medications (ASMs) doses are common during long-term or lifelong antiepilepsy treatment. This study aims to explore optimal individualized remedial dosing regimens for delayed or missed doses of 11 commonly used ASMs. METHODS: To explore remedial dosing regimens, Monte Carlo simulation was used based on previously identified and published population pharmacokinetic models. Six remedial strategies for delayed or missed doses were investigated. The deviation time outside the individual therapeutic range was used to evaluate each remedial regimen. The influences of patients' demographics, concomitant medication, and scheduled dosing intervals on remedial regimens were assessed. RxODE and Shiny in R were used to perform Monte Carlo simulation and recommend individual remedial regimens. RESULTS: The recommended remedial regimens were highly correlated with delayed time, scheduled dosing interval, and half-life of the ASM. Moreover, the optimal remedial regimens for pediatric and adult patients were different. The renal function, along with concomitant medication that affects the clearance of the ASM, may also influence the remedial regimens. A web-based dashboard was developed to provide individualized remedial regimens for the delayed or missed dose, and a user-defined module with all parameters that could be defined flexibly by the user was also built. DISCUSSION: Monte Carlo simulation based on population pharmacokinetic models may provide a rational approach to propose remedial regimens for delayed or missed doses of ASMs in pediatric and adult patients with epilepsy.