Quantitation of levetiracetam concentrations in plasma and saliva samples by ultra-performance liquid chromatography-tandem mass spectrometry: Application to therapeutic drug monitoring for pregnant women with epilepsy.

Although levetiracetam (LEV) has favorable linear pharmacokinetic properties, therapeutic drug monitoring (TDM) is necessary for pregnant women with epilepsy. This study aims to build a simple, reliable, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining LEV concentrations in plasma and saliva samples, to support the routine TDM of LEV in Chinese pregnant women with epilepsy. The stable isotope-labeled LEV-d6 was used as the internal standard. The extracted samples were analyzed using a UPLC-MS/MS system with positive electrospray ionization. Mobile phase A was water containing 5 mM ammonium acetate and 0.1% formic acid, and phase B was 1:1 methanol-acetonitrile with 0.1% formic acid. The method was validated and utilized to determine LEV concentrations in non-pregnant and pregnant patients with epilepsy. The developed method was validated in both plasma and saliva samples over a concentration range of 0.1-50 µg/mL. The intra- and inter-batch accuracy for LEV ranged from -7.0% to 2.9%, with precisions between 2.7% and 9.3%. In pregnant patients, the mean dose-standardized LEV trough plasma concentrations were significantly lower than those in non-pregnant patients (4.73 ± 2.99 vs. 7.74 ± 3.59 ng/mL per mg/day; P < 0.0001). It is recommended that the TDM of LEV should be routinely performed during the different stages of pregnancy.

Whole-cycle management of women with epilepsy of child-bearing age: ontology construction and application.

BACKGROUND: The effective management of epilepsy in women of child-bearing age necessitates a concerted effort from multidisciplinary teams. Nevertheless, there exists an inadequacy in the seamless exchange of knowledge among healthcare providers within this context. Consequently, it is imperative to enhance the availability of informatics resources and the development of decision support tools to address this issue comprehensively. MATERIALS AND METHODS: The development of the Women with Epilepsy of Child-Bearing Age Ontology (WWECA) adhered to established ontology construction principles. The ontology's scope and universal terminology were initially established by the development team and subsequently subjected to external evaluation through a rapid Delphi consensus exercise involving domain experts. Additional entities and attribute annotation data were sourced from authoritative guideline documents and specialized terminology databases within the respective field. Furthermore, the ontology has played a pivotal role in steering the creation of an online question-and-answer system, which is actively employed and assessed by a diverse group of multidisciplinary healthcare providers. RESULTS: WWECA successfully integrated a total of 609 entities encompassing various facets related to the diagnosis and medication for women of child-bearing age afflicted with epilepsy. The ontology exhibited a maximum depth of 8 within its hierarchical structure. Each of these entities featured three fundamental attributes, namely Chinese labels, definitions, and synonyms. The evaluation of WWECA involved 35 experts from 10 different hospitals across China, resulting in a favorable consensus among the experts. Furthermore, the ontology-driven online question and answer system underwent evaluation by a panel of 10 experts, including neurologists, obstetricians, and gynecologists. This evaluation yielded an average rating of 4.2, signifying a positive reception and endorsement of the system's utility and effectiveness. CONCLUSIONS: Our ontology and the associated online question and answer system hold the potential to serve as a scalable assistant for healthcare providers engaged in the management of women with epilepsy (WWE). In the future, this developmental framework has the potential for broader application in the context of long-term management of more intricate chronic health conditions.

China's energy-water-land system co-evolution under carbon neutrality goal and climate impacts.

China's 2060 carbon neutrality goal has significant implications for energy, water, and land systems. However, the multi-sector dynamics among China's energy-water-land system have rarely been examined explicitly. This study adopts an integrated assessment framework to simulate China's energy-water-land system co-evolution under alternative carbon neutrality scenarios and climate impacts. Results show that although the net zero emission target provides the incentive for the energy system to move away from fossil fuels, total water withdrawal will increase due to the deployment of nuclear, bioenergy, and coal power plants with carbon capture and storage. Diversifying the negative emission technologies, by leveraging direct air capture technology, can alleviate the potential water stress and land use conflicts, which would otherwise be exacerbated by large-scale deployment of afforestation and bioenergy with carbon capture and storage. Northwest and northeast regions of China are the hotspots experiencing water withdrawal increases, while Bohai Rim and coastal regions are identified to experience fierce land competition. This study demonstrates the potential for general applicability to carry out resource planning and policy evaluation from the multi-sector coordination perspective.

BRD4 is involved in viral exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Our previous studies have suggested that bromodomain protein 4 (BRD4) is increased in the lung of stable chronic obstructive pulmonary disease (COPD) patients, which has been shown to be involved in inflammatory responses. We investigated its role in the viral exacerbation of COPD. METHODS: BRD4, interleukin (IL)-6 and IL-8 were measured in the blood and sputum of stable COPD patients and patients with viral exacerbation. Mice were exposed to cigarette smoke (CS) and/or infected with influenza virus as an in vivo model. BRD4, IL-6 and keratinocyte-derived chemokine (KC) were measured in the lung. BEAS-2B cells were treated with CS extract and/or influenza virus as an in vitro model. BRD4, IL-6 and IL-8 were measured in the cells and/or culture supernatant. RESULTS: BRD4 was increased in COPD patients with viral exacerbation compared with those in stable condition and its expression was correlated with IL-6 and IL-8 expression. Inflammatory cells, IL-6, KC and BRD4 were synergistically induced in the lung of mice by viral infection and CS exposure, and the former three were decreased by JQ1 (BRD4 inhibitor) treatment. IL-6, IL-8 and BRD4 were significantly induced by CS extract and influenza virus in bronchial epithelial cells, and this upregulation was suppressed by knockdown of BRD4 expression. CONCLUSIONS: Our findings indicate that CS and viruses may synergistically induce IL-6 and IL-8 expression through their synergistic induction of BRD4 expression, which might contribute to the enhanced inflammatory response in the viral exacerbation of COPD.

Antinuclear Antibodies in Erythema Multiforme: Transient Occurrence During Acute Illness.

BACKGROUND: Children with target lesions are frequently diagnosed with erythema multiforme (EM). EM was not previously thought to be associated with any specific autoimmune serological abnormality. METHODS: We report the case of a 7-year-old girl who developed rashes all over her body with target shaped lesions. Based on clinical appearance and medical history, she was diagnosed with severe erythema multiforme and treated with methylprednisolone. Relevant laboratory tests were performed at admission. RESULTS: At the height of her infection, the antinuclear antibody (ANA) test showed a positive ANA with a titer of 1:100 (speckled pattern) and positive anti-SSA and anti-Ro-52 antibodies. Then she was adjusted for medication. After a week, the infection was relieved, and the re-examination was negative for ANA, anti-SSA, and anti-Ro-52 antibodies. CONCLUSIONS: In previously reported EM cases, ANA is generally not considered to be present. The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of EM infection. Its correlation with infection severity warrants further research on the mechanism of autoantibody formation in EM.

A pilot study on identifying gene signatures as markers for predicting patient response to antiseizure medications.

The majority of the biomarkers were associated with the diagnosis of epilepsy and few of them can be applied to predict the response to antiseizure medications (ASMs). In this study, we identified 26 significantly up-regulated genes and 32 down-regulated genes by comparing the gene expression profiles of patients with epilepsy that responded to valproate with those without applying any ASM. The results of gene set enrichment analysis indicated that the ferroptosis pathway was significantly impacted (p = 0.0087) in patients who responded to valproate. Interestingly, the gene NCOA4 in this pathway exhibited significantly different expression levels between the two groups, indicating that NCOA4 could serve as a potential biomarker to better understand the mechanism of valproate resistance. In addition, six up-regulated genes SF3A2, HMGN2, PABPN1, SSBP3, EFTUD2, and CREB3L2 as well as six down-regulated genes ZFP36L1, ACRC, SUB1, CALM2, TLK1, and STX2 also showed significantly different expression patterns between the two groups. Moreover, based on the gene expression profiles of the patients with the treatment of valproate, carbamazepine, and phenytoin, we proposed a strategy for predicting the response to the ASMs by using the Connectivity Map scoring method. Our findings could be helpful for better understanding the mechanisms of drug resistance of ASMs and improving the clinical treatment of epilepsy.

A Two-Stage Voting-Boosting Technique for Ensemble Learning in Social Network Sentiment Classification.

In recent years, social network sentiment classification has been extensively researched and applied in various fields, such as opinion monitoring, market analysis, and commodity feedback. The ensemble approach has achieved remarkable results in sentiment classification tasks due to its superior performance. The primary reason behind the success of ensemble methods is the enhanced diversity of the base classifiers. The boosting method employs a sequential ensemble structure to construct diverse data while also utilizing erroneous data by assigning higher weights to misclassified samples in the next training round. However, this method tends to use a sequential ensemble structure, resulting in a long computation time. Conversely, the voting method employs a concurrent ensemble structure to reduce computation time but neglects the utilization of erroneous data. To address this issue, this study combines the advantages of voting and boosting methods and proposes a new two-stage voting boosting (2SVB) concurrent ensemble learning method for social network sentiment classification. This novel method not only establishes a concurrent ensemble framework to decrease computation time but also optimizes the utilization of erroneous data and enhances ensemble performance. To optimize the utilization of erroneous data, a two-stage training approach is implemented. Stage-1 training is performed on the datasets by employing a 3-fold cross-segmentation approach. Stage-2 training is carried out on datasets that have been augmented with the erroneous data predicted by stage 1. To augment the diversity of base classifiers, the training stage employs five pre-trained deep learning (PDL) models with heterogeneous pre-training frameworks as base classifiers. To reduce the computation time, a two-stage concurrent ensemble framework was established. The experimental results demonstrate that the proposed method achieves an F1 score of 0.8942 on the coronavirus tweet sentiment dataset, surpassing other comparable ensemble methods.

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Signal transducer and activator of transcription 5 (STAT5) can be involved in the processes such as cell proliferation, differentiation, apoptosis, and hematopoiesis, and its dysregulation is closely associated with the development and progression of malignant tumors including leukemia and may affect the treatment outcome and prognosis of pediatric patients. Identification of STAT5 can facilitate targeted therapy to improve the response rate of children with acute lymphoblastic leukemia. This article reviews the impact of STAT5 on the development/progression, targeted therapy strategies and the prognosis of childhood acute lymphoblastic leukemia.

A Rare Antinuclear Antibody Fluorescence Pattern Induced by Rodenticides: a Case Report.

BACKGROUND: Warfarin and superwarfarins, which belong to anticoagulants, are also widely used as rodenticides worldwide. Cases of accidental ingestion of these kinds of rodenticides often occur, and the patients usually have clinical symptoms of various systemic bleeding which are, in serious cases, life threatening. METHODS: We reported a 12-year-old boy poisoned by superwarfarins. He was initially diagnosed with coagulation disorder induced by rodenticides and was treated with vitamin K. A month after the onset of the disease, the patient was further treated in our hospital. We improved his relevant laboratory tests and found that his antinuclear antibody (ANA) and anti-SSA antibodies were positive. After the patient was cured and discharged, the result of ANA turned negative four months later. RESULTS: The ANA fluorescence pattern of the patient presented a rare cytoplasmic granular type with low titer, which appeared when the patient was poisoned and disappeared after cured. In the previously reported cases of rodenticides poisoning, ANA-positive individuals are rare, and this kind of fluorescence pattern has not been reported before. CONCLUSIONS: During the diagnosis and treatment of anticoagulant rodenticides poisoning patients, the monitoring of coagulation function is important, but other laboratory tests should also be considered to avoid missing some suggestive positive results.

Evaluation of Blood Markers at Admission for Predicting Community Acquired Pneumonia in Chronic Obstructive Pulmonary Disease.

Acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) and community acquired pneumonia (CAP) are two common acute attacks in COPD patients and it is not always easy to determine whether a COPD patient at admission has parenchymal infection or bronchial infection. Comprehensive comparison between AECOPD patients and CAP patients with COPD (COPD + CAP) can help us understand them better. We retrospectively collected the medical records of AECOPD and COPD + CAP patients. Systemic inflammation, eosinophilic inflammation, damage to other organs, common chronic comorbidities, structural changes, phenotype and endotype distributions and coagulation functions between two groups were compared and correlations of these characteristics in total subjects, AECOPD patients and COPD + CAP patients were analyzed. Logistic regression analysis was performed to select helpful biomarkers for distinguishing between them. Receiver operator characteristic (ROC) curve was plotted to assess the diagnostic value of selected biomarkers and their combination. A nomogram was established for the differential diagnosis of AECOPD and COPD + CAP. A total of 206 patients were included into our analysis. In these subjects, 104 patients were classified as AECOPD group and 102 patients were considered to have COPD + CAP mainly based on their chest CT scan results. The counts of eosinophils (EOS), basophils (BAS) and lymphocytes (LYM) and percentage of total white blood cell count, hemoglobin and hematocrit were increased in AECOPD patients compared with COPD + CAP patients. The counts of neutrophils (NEU) and percentage of total white blood cell count, C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR), fibrinogen, D-dimer and N-Terminal pro-brain natriuretic peptide (NT-proBNP) levels were increased in COPD + CAP patients. After logistic regression analysis, EOS < 0.5 × 109/L, ESR ≥ 8 mm/H and NT-proBNP ≥ 100 pg/mL were selected as helpful biomarkers for diagnosis of COPD + CAP instead of AECOPD. Area under the ROC curve (AUC) of the combination of selected biomarkers was 0.764(0.698-0.829). A nomogram was established and the calibration curve suggested that fitting efficiency of the nomogram was good. AECOPD and COPD + CAP are markedly different, mainly reflected in eosinophilic inflammation, systemic inflammation and coagulation function. Correlations between some common inflammatory biomarkers are also different in the two groups. A nomogram was established to offer help to clinicians for differential diagnosis of these two diseases.

Photodetection system immune to amplitude-to-phase conversion noise for ultralow noise photonic microwave generation.

Microwave signals generated by photodetection of the pulse train of an optical frequency comb locked to an ultrastable laser have ultrahigh spectral purity and frequency stability. The amplitude-to-phase noise conversion (APC) that occurs in the photodetection, however, degrades the phase noise of the generated microwave signal over the range from tens of hertz to several kilohertz. Here we demonstrate active APC compensation by precisely tuning the bias voltage applied to a photodetector using the APC coefficient measured by comparing with a reference photodetector. In this scheme, the APC was dramatically reduced and a long-term steady rejection of the laser relative intensity noise of more than 60 dB was achieved.

Three-year customer satisfaction survey in laboratory medicine in a Chinese university hospital.

BACKGROUND: Customer satisfaction is a key quality indicator of laboratory service. Patients and physicians are the ultimate customers in medical laboratory, and their opinions are essential components in developing a customer-oriented laboratory. METHODS: A longitudinal investigation of customer satisfaction was conducted through questionnaires. We designed two different questionnaires and selected 1200 customers (600 outpatients and 600 physicians) to assess customer satisfaction every other year from 2012 to 2016. Items with scores <4 were considered unsatisfactory, and corrective actions should be taken. RESULTS: The completion rates of physicians were 96.8% in 2012, 97% in 2014 and 96.5% in 2016, whereas the rates of patients were 95.3%, 96.2% and 95.2%, respectively. In 2012, the most dissatisfaction items were test turnaround time (3.77 points) and service attitude (3.87 points) from physicians, whereas waiting time (3.58 points) and examination environment (3.64 points) were the most dissatisfaction items from patients. After corrective actions were taken, the result of satisfaction in 2014 was better, which illustrated our strategy was effective. However, some items remained to be less than 4, so we repeated the survey after modifying questionnaires in 2016. However, the general satisfaction points of the physicians and patients reduced in 2016, which reminded us of some influential factors we had neglected. CONCLUSIONS: By using dynamic survey of satisfaction, we can continuously find deficiencies in our laboratory services and take suitable corrective actions, thereby improving our service quality.

The effects of lead on GABAergic interneurons in rodents.

Lead is a heavy metal that affects various systems and organs in the body, especially the nervous system. In this study, the in vivo and in vitro effects of lead on neurons were analyzed. We divided mouse pups into three groups based on the concentration of lead exposure: the control group, the low-dose group, and the high-dose group. Changes in behavior (measured by an open-field test and a tail suspension test), blood lead levels (measured by atomic absorption spectrophotometry), the number of GABAergic interneurons (measured by immunohistochemistry), gene expression (measured by qRT-PCR), and DNA methylation (measured by pyrosequencing) were determined in the three groups. The lead-exposed pups showed significantly higher blood lead levels ( p < 0.001). Lead exposure caused hyperactivity and reduced the body weight of the exposed mice compared with that of the controls. The lead-exposed groups showed significantly lower numbers of parvalbumin and neuropeptide Y interneurons and lower expression levels of distal-less homeobox ( Dlx) 1, 2, 5, and 6 genes in the cerebral cortex. To further clarify the mechanism of Dlx gene downregulation, we selected the GE6 cell line, which can differentiate into various subtypes of GABAergic interneurons, for in vitro experiments. We found that high levels of lead also inhibited the expression of Dlx 1/ 2/ 5/ 6 in vitro, but DNA methylation levels were not changed in the GE6 cell line. Furthermore, lead exposure significantly decreased the expression of Olig1 and Ki67 and increased that of Tubb3 in vitro. The present study revealed that lead exposure can alter behaviors, reduce the number of GABAergic interneurons, and change the expression of some important genes in neuronal cells.

Reference Intervals for Thyroid Function and the Negative Correlation between FT4 and HbA1c in Pregnant Women of West China.

BACKGROUND: It is necessary to establish the reference intervals of thyroid hormones in the three trimesters and postpartum period of healthy pregnant women in western China. Thyroid hormones play important roles in metabolic processes. METHODS: The concentrations of TPOAbs, TSH, and FT4 were measured by an ADVIA Centaur 2000 and HbA1c in the second trimester was measured by BIO-RAD D-10. RESULTS: 3435 pregnant women and 834 non-pregnant women were selected to establish the reference intervals. The level of TSH was the lowest (from 0.051 to 4.489 mIU/L) in the first trimester (p < 0.001) and FT4 was lower in the second (from 10.97 to 15.49 pmol/L) or third trimester (from 9.49 to 16.25 pmol/L) compared with the other periods (p < 0.001). 20% of participants had TSH levels below the lower limit of the manufacturer's reference interval (0.55 mIU/L) in the first trimester. 6.9% in the second and 16.1% of participants in the third trimester had FT4 levels below the lower limit of the manufacturer's reference interval. In multiple regression analyses, FT4 was independently associated with HbA1c (OR = 0.191; 95% CI 0.052, 0.698; p = 0.012), BMI (OR = 0.697; 95% CI 0.525, 0.927; p = 0.013), and TSH (OR = 0.647; 95% CI 0.428, 0.978; p = 0.039). Nonpredictive variable was age. CONCLUSIONS: The established reference intervals of TSH and FT4 reflected the changes of thyroid hormones veritably during gestation, and concentrations of FT4 in the first trimester were negatively correlated with HbA1c in the second trimester.

Monitoring levetiracetam concentration in saliva during pregnancy is stable and feasible.

AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.

Causal link between oxidative stress and epilepsy: A two-sample Mendelian randomization study.

BACKGROUND: Although a growing body of research has indicated a strong link between oxidative stress and epilepsy, the exact nature of their interaction remains elusive. To elucidate this intricate relationship, we conducted a bidirectional Mendelian randomization (MR) analysis employing two independent datasets. METHODS: A two-sample MR analysis was performed using instrumental variables derived from genome-wide association study summary statistics of oxidative stress injury biomarkers (OSIB) and epilepsy. The OSIBs were selected from eight primary metabolic pathways associated with oxidative stress. Additionally, seven distinct epilepsy phenotypes were considered, which encompassed all epilepsy, generalized epilepsy, generalized tonic-clonic seizures, focal epilepsy, focal epilepsy with hippocampal sclerosis (focal HS), focal epilepsy with lesions other than HS (focal NHS), and lesion-negative focal epilepsy. Causal estimates were computed using the inverse-variance weighted method or the Wald ratio method, and the robustness of causality was assessed through sensitivity analyses. RESULTS: For OSIB and epilepsy, 520 and 23 genetic variants, respectively, were selectively extracted as instrumental variants. Genetically predicted higher kynurenine level was associated with a decreased risk of focal epilepsy (odds ratio [OR] 1.950, 95% CI 1.373-2.528, p = .023) and focal NHS (OR 1.276, 95% CI 1.100-1.453, p = .006). For reverse analysis, there was a suggestive effect of focal NHS on urate (OR 1.19 × 1015, 95% CI 11.19 × 1015 to 1.19 × 1015, p = .0000746) and total bilirubin (Tb) (OR 4.98, 95% CI 3.423-6.543, p = .044). In addition, genetic predisposition to focal HS was associated with higher Tb levels (OR 9.83, 95% CI 7.77-11.888, p = .034). CONCLUSION: This MR study provides compelling evidence of a robust association between oxidative stress and epilepsy, with a notable emphasis on a causal relationship between oxidative stress and focal epilepsy. Additional research is warranted to confirm the connection between oxidative stress and the risk of epilepsy and to unravel the underlying mechanisms.

A disulfiram derivative against lung cancer via the Notch signaling pathway without neurotoxicity and hepatotoxicity.

The exploration of novel anti-lung cancer small-molecule drugs is important for drug resistance and adverse effects of chemotherapeutic drugs in current clinics. Disulfiram (DSF), as an antidote, has been proven to have excellent antitumor effects in combination with copper (Cu). However, the risk for potential neurotoxicity and hepatotoxicity in clinical use, as well as its poor water solubility, limits its use. In this study, we identified a DSF derivative, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine, which could greatly increase the water solubility by converting it to a calcium salt (DS-NAC). The anti-lung cancer pharmacodynamic studies in vitro of DS-NAC were evaluated and a mouse model of lung cancer in situ was established to explore the therapeutic effects of DS-NAC compared with DSF and oxaliplatin (OXA). The results demonstrated that DS-NAC combined with Cu had superior cytotoxicity to DSF and OXA in the CCK8 assay against lung cancer cells, and exhibited potent anti-metastatic, epithelial-mesenchymal transition inhibition. In addition, DS-NAC showed better antitumor effects than DSF and comparable effects to OXA in lung cancer in situ model. In terms of the antitumor mechanism, we discovered that DS-NAC in combination with Cu exerted a greater inhibitory effect on the Notch pathway than DSF, which may account for its excellent antitumor effects. Finally, we verified the safety of DS-NAC in vivo, showing lower hepatotoxicity and neurotoxicity compared with DSF and OXA. DS-NAC is a promising anti-lung cancer drug with a favorable safety profile.

Adaptive Dosage Strategy of Levetiracetam in Chinese Epileptic Patients: Focus on Pregnant Women.

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30-3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4-47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy.

Neurosyphilis Presenting as Psychiatric Symptoms at Younger Age: A Case Report.

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

Global burden and management of women with epilepsy in pregnancy: A modeling study.

BACKGROUND: Most pregnant women with epilepsy do not receive proper medical care, which creates a special burden worldwide. We aimed to qualify this special global burden and assess the impact of different clinical management strategies to reduce it. METHODS: The data used in this study were extracted from articles published between 2005 and 2022. We calculated the economic costs associated with major burdens experienced by pregnant women with epilepsy. We developed a microsimulation model to estimate the different effects of various interventions and their combinations as integrated strategies for pregnant women with epilepsy and related burden reduction. We also compared the regional differences in disease burden and interventions. FINDINGS: The total economic burden for pregnant women with epilepsy is estimated to reach $1.8 billion globally annually, which is more than three times the burden for epilepsy alone. Folic acid supplementation is projected to be the most effective intervention, with a 9.1% reduction in major congenital malformations, a 14.9% reduction in autism spectrum disorder, and a 10.8% reduction in offspring-related economic burden globally annually. Integrated strategies are associated with a reduced economic burden of up to $37.7 million annually globally. Folic acid supplementation is the most effective intervention in high- and upper-middle-income countries, whereas changes in antiseizure medication prescriptions are more effective in lower-middle- and low-income countries. CONCLUSION: This study highlights the huge burden for pregnant women with epilepsy and actions that must be taken to improve their quality of life. FUNDING: This work was supported by the Sichuan Science and Technology Program (2023YFS0047).