The role of alexithymia in suicide ideation among Taiwanese army military personnel: A serial mediation model investigating the effects of perceived stress and depression.

Maintaining the good mental health of Taiwanese military personnel is crucial, especially in light of incidents such as the Taiwan Strait crisis. Suicide is a leading cause of death among military personnel and alexithymia is a significant risk factor for suicidal ideation. However, the mechanisms linking alexithymia and suicidal ideation in this psychologically burdened population remain poorly understood. In total, 863 voluntary army military personnel from Taiwanese reserve brigades and combined-arms brigades were enroled between May 2020 and February 2021. Structured questionnaires about alexithymia, perceived stress, depression, suicidal ideation, and background characteristics were used. Mediation analyses were conducted to examine the serial mediation roles of perceived stress and depression in the relationship between alexithymia and suicidal ideation. Significant positive correlations were observed between alexithymia, perceived stress, depression, and suicidal ideation in bivariate analyses. Serial mediation analyses revealed that alexithymia significantly predicted higher levels of perceived stress, subsequently leading to depressive symptoms, which were associated with suicidal ideation. Depression served as a significant mediator between alexithymia and suicidal ideation. The strongest mediating effect (71.4%) was observed in the pathway from alexithymia through perceived stress and depression to suicidal ideation. Limitations included the utilization of cross-sectional data and a reliance on retrospective self-report measures. Perceived stress and depression were identified as serial mediators in the association between alexithymia and suicidal ideation. Clinically, it is crucial to prioritise interventions that target emotional regulation skills and assess the presence of alexithymia to effectively reduce suicidal ideation in military personnel.

An investigation of water status in gelatin methacrylate hydrogels by means of water relaxometry and differential scanning calorimetry.

The relationship between molecular structure and water dynamics is a fundamental yet often neglected subject in the field of hydrogels for drug delivery, bioprinting, as well as biomaterial science and tissue engineering & regenerative medicine (TE&RM). Water is a fundamental constituent of hydrogel systems and engages via hydrogen bonding with the macromolecular network. The methods and techniques to measure and reveal the phenomena and dynamics of water within hydrogels are still limited. In this work, differential scanning calorimetry (DSC) was used as a quantitative method to analyze freezable (including free and freezable bound) and non-freezable bound water within gelatin methacrylate (GelMA) hydrogels. Nuclear magnetic resonance (NMR) is a complementary method for the study of water behavior and can be used to measure the spin-relaxation of water hydrogen nuclei, which is related to water dynamics. In this research, nuclear magnetic resonance relaxometry was employed to investigate the molecular state of water in GelMA hydrogels using spin-lattice (T1) and spin-spin (T2) spin-relaxation time constants. The data displays a trend of increasing bound water content with increasing GelMA concentration. In addition, T2 values were further applied to calculate microviscosity and translational diffusion coefficients. Water relaxation under various chemical environments, including different media, temperatures, gelatin sources, as well as crosslinking effects, were also examined. These comprehensive physical data sets offer fundamental insight into biomolecule transport within the GelMA hydrogel system, which ultimately are important for drug delivery, bioprinting, as well as biomaterial science and TE&RM communities.

Margin to depth of invasion ratio as an indicator for stratifying close margins in early-stage oral squamous cell carcinoma.

OBJECTIVES: In early-stage oral squamous cell carcinoma (OSCC) patients, whether the margin-to-depth-of-invasion ratio (MDR) can assist in stratifying the prognosis remains unclear. METHODS: Patients diagnosed with early stage OSCC at National Taiwan University Hospital between January 2007 and December 2021 were reviewed. Patients with margin > 1 mm were classified into two groups: MDR < 0.5 and MDR ≥ 0.5. RESULTS: We analyzed 911 pT1-2N0M0 OSCC patients, 723 (79.36 %) with MDR ≥ 0.5 and 188 (20.64 %) with MDR < 0.5. Patients in the MDR < 0.5 group displayed a significantly higher local recurrence rate (odds ratio 2.81, p = 0.002) compared with MDR ≥ 0.5 group. The 5-year disease-free survival were 80.8 % for clear margin, 76.3 % for close margin (MDR ≥ 0.5), and 65.2 % for close margin (MDR < 0.5). The overall survival displayed a similar pattern, with 5-year rates of 88.3 % for clear margin, 86.8 % for close margin (MDR ≥ 0.5), and 75.0 % for close margin (MDR < 0.5). There were no significant overall survival differences between the two MDR ≥ 0.5 groups, but both were significantly superior to patients with MDR < 0.5 (p = 0.001; p = 0.01). After multivariant cox analysis, MDR < 0.5 was a significant risk factor for disease-free survival (p < 0.001). CONCLUSION: For early stage OSCC patients without positive margin (≦1mm), the survival outcome between MDR ≥ 0.5 group and MDR < 0.5 group was significantly different. The MDR < 0.5 group had significantly higher risk of local recurrence that may warrant adjuvant treatment.

Detecting shifts in nonlinear dynamics using Empirical Dynamic Modeling with Nested-Library Analysis.

Abrupt changes in system states and dynamical behaviors are often observed in natural systems; such phenomena, named regime shifts, are explained as transitions between alternative steady states (more generally, attractors). Various methods have been proposed to detect regime shifts from time series data, but a generic detection method with theoretical linkage to underlying dynamics is lacking. Here, we provide a novel method named Nested-Library Analysis (NLA) to retrospectively detect regime shifts using empirical dynamic modeling (EDM) rooted in theory of attractor reconstruction. Specifically, NLA determines the time of regime shift as the cutting point at which sequential reduction of the library set (i.e., the time series data used to reconstruct the attractor for forecasting) optimizes the forecast skill of EDM. We illustrate this method on a chaotic model of which changing parameters present a critical transition. Our analysis shows that NLA detects the change point in the model system and outperforms existing approaches based on statistical characteristics. In addition, NLA empirically detected a real-world regime shift event revealing an abrupt change of Pacific Decadal Oscillation index around the mid-1970s. Importantly, our method can be easily generalized to various systems because NLA is equation-free and requires only a single time series.

Therapeutic drug monitoring of perampanel: Clinical utility and impact of co-medication on pharmacokinetic variability.

Background: Perampanel (PER) is a newly developed antiseizure medication (ASM). This study aimed to determine the utilization of therapeutic drug monitoring (TDM) for PER in a real-world clinical setting and investigate the influence of concomitant use of ASMs on the plasma concentration profile of PER. Method: We analyzed data from the Chang Gung Research Database, which is the largest multi-institutional electronic medical records database in Taiwan. The main outcomes were the comparisons of PER plasma concentration and the ratio of concentration to the weight-adjusted dose (C/D; [ng/mL]/[mg/kg/d]) among patients received TDM of different clinical indication and among different ASM co-medication subgroups. Results: Overall, 88 plasma samples were collected from 66 epilepsy patients treated with PER. The majority of patients (77.3 %) underwent PER TDM owing to poorly controlled seizures. There was a trend toward a higher plasma concentration and C/D ratio in those suspected of having PER toxicity owing to adverse events than of other indications. The PER concentration exhibited dose linearity. The mean PER plasma concentrations in patients co-medicated with enzyme-inducing ASMs were significantly lower than those in the patients who were not prescribed enzyme-inducing or enzyme-inhibiting ASMs, and co-medication with carbamazepine (CBZ) resulted in a significant reduction in the PER concentration. Conclusion: PER concentration exhibited a linear regression relationship with PER dose, and the plasma concentration of the drug was highly susceptible to the drug's interactions with enzyme-inducing ASMs. TDM with clear indication could help determine the influence of ASMs used concomitantly on PER concentrations and guide clinical adjustments.

Characteristics of acute ischemic stroke in patients with Nephrotic syndrome.

The incidence of ischemic stroke (IS) is higher in nephrotic syndrome (NS) patients compared to general population. However, there is limited information on the specific characteristics to stroke patients with NS. In this study, we aimed to examine the clinical manifestations of acute IS in a large group of NS patients, comparing to those without NS. We conducted a retrospective cohort study to compare the clinical presentations of acute IS in patients with and without NS. This study was a multi-institutional study and used data from Chang Gung Research Database of Taiwan from 1 January 2001, to 31 December 2017. A total of 233 IS patients with NS and 1358 IS patients without NS were enrolled. The median age of participants was 68 (range: 59-79) years. The risk of dependent functional status (modified Rankin Scale score≧3) after IS was higher in NS patients compared to those without NS (Odd ratio (OR) 4.02, 95% confidence interval (CI) 2.39 to 6.76, p < 0.001), particularly in stroke subtypes as small-artery occlusion (OR 8.02, 95% CI 3.94 to 16.32, p < 0.001), and stroke of undetermined etiology (OR 2.47, CI 1.06 to 5.76, p = 037). The risks of mortality or stroke recurrence within 30 days were similar between the two groups for all stroke subtypes. In conclusion, NS was associated with a higher risk of functional dependence following IS. Intensive treatment and rehabilitation should be considered for IS patients with NS.

Clinical impact of therapeutic drug monitoring for newer anti-seizure medications in patients with epilepsy: A real-world observation study.

BACKGROUND: The clinical value of therapeutic drug monitoring (TDM) for newer anti-seizure medications (ASMs) remains uncertain. This study aimed to assess the impact of newer ASM TDM on clinical decision making in patients with epilepsy. METHODS: We retrospectively identified all plasma requests for newer ASM level measurement as part of routine clinical management in the outpatient departments of seven medical institutes across Taiwan between September 2016 and May 2019. Data collected from reviewed medical records included clinical and medication details, indications for TDM request, test results, interpretation, and impact on patient management. RESULTS: A total of 682 visits with 1051 plasma samples were included. The most frequently analyzed ASMs were levetiracetam (36.1%), oxcarbazepine (18.4%), and lamotrigine (12.0%). Reasons for TDM included poorly controlled seizures (55.3%), concerns about drug-drug interactions (12.3%), and suspicion of drug overdose (10.6%). 68.8% of samples were within the orienting therapeutic range, even for patients with poorly controlled seizures. TDM for non-adherence concerns showed 54.3% below the orienting therapeutic range, while ASM-related adverse events assessment only 8.9% showed levels exceeding the orienting therapeutic range. Following TDM results, 64.2% of cases had medication adjustments, mainly dosage increases. Overall, 55.9% of newer ASM TDM visit showed improved outcomes, including reduced seizures (47.5%) and fewer ASM-related side effects (8.4%). CONCLUSIONS: These findings suggest that appropriate utilization of TDM for newer ASMs provides clinical benefits in adjunct to complement clinical decision making in the management of epilepsy patients in a real-world clinical setting.

Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action.

Background: Combination therapy with antiseizure medications (ASMs) is a rational strategy if monotherapy cannot effectively control seizures, thereby aiming to improve tolerance and treatment persistence. Objectives: To compare the efficacy of different ASM combinations among patients. Design: Patients with epilepsy on monotherapy who had a second ASM added as concomitant two-drug therapy from January 2009 to May 2019 in the Chang Gung Research Database, Taiwan, were included in the analysis. Methods: ASM combinations were compared based on their primary mechanism of action (MoA) which are as follows: gamma-aminobutyric acid receptor (G), sodium channel blocker (SC), synaptic vesicle protein 2A (SV2), calcium channel blocker (C), and multiple mechanisms (M). Treatment persistence was compared, and the predictors of persistence were analyzed. Results: In total, 3033 patients were enrolled in this study. Combined ASMs with different MoAs had significantly longer treatment persistence than ASMs with similar MoAs, specifically SC and M combinations. Patients receiving combined ASMs with different MoAs were less likely to discontinue treatment [adjusted hazards ratio: 0.83 (95% CI: 0.75-0.93), p < 0.001]. Among all combinations, the SC + SV2 combination had the longest treatment persistence (mean ± SD: 912.7 ± 841.6 days). Meanwhile, patients receiving the G combination had a higher risk of treatment discontinuation than those receiving the SC + SV2 combination. Underlying malignancies were associated with an increased risk of treatment discontinuation across all MoA categories. Male patients receiving the SC, SV2, and M combinations were more likely to discontinue treatment than female patients. Moreover, patients with renal disease were more likely to discontinue treatment with the SV2 combinations. Conclusion: ASM combinations with different MoAs had superior efficacy and tolerability to ASM combinations with similar MoAs, particularly SC and M combinations. In our cohort, factors associated with treatment discontinuation included underlying malignancy, male sex, and renal disease. These findings may provide valuable insights into the use of ASM combinations if monotherapy cannot adequately control seizures.

Unraveling the promoter effect and the roles of counterion exchange in glycosylation reaction.

The stereoselectivity of glycosidic bond formation continues to pose a noteworthy hurdle in synthesizing carbohydrates, primarily due to the simultaneous occurrence of SN1 and SN2 processes during the glycosylation reaction. Here, we applied an in-depth analysis of the glycosylation mechanism by using low-temperature nuclear magnetic resonance and statistical approaches. A pathway driven by counterion exchanges and reaction byproducts was first discovered to outline the stereocontributions of intermediates. Moreover, the relative reactivity values, acceptor nucleophilic constants, and Hammett substituent constants (σ values) provided a general index to indicate the mechanistic pathways. These results could allow building block tailoring and reaction condition optimization in carbohydrate synthesis to be greatly facilitated and simplified.

Brain computed tomography reading of stroke patients by resident doctors from different medical specialities: An eye-tracking study.

BACKGROUND: Using the eye-tracking technique, our work aimed to examine whether difference in clinical background may affect the training outcome of resident doctors' interpretation skills and reading behaviour related to brain computed tomography (CT). METHODS: Twelve resident doctors in the neurology, radiology, and emergency departments were recruited. Each participant had to read CT images of the brain for two cases. We evaluated each participant's accuracy of lesion identification. We also used the eye-tracking technique to assess reading behaviour. We recorded dwell times, fixation counts, run counts, and first-run dwell times of target lesions to evaluate visual attention. Transition entropy was applied to assess the temporal relations and spatial dynamics of systematic image reading. RESULTS: The eye-tracking results showed that the image reading sequence examined by transition entropy was comparable among resident doctors from different medical specialties (p = 0.82). However, the dwell time of the target lesions was shorter for the resident doctors from the neurology department (4828.63 ms, p = 0.01) than for those from the resident doctors from the radiology (6275.88 ms) and emergency (5305.00 ms) departments. The eye-tracking results in individual areas of interest only showed differences in the eye-tracking performance of the first-run dwell time (p = 0.05) in the anterior cerebral falx. DISCUSSION: Our findings demonstrate that resident doctors from different medical specialties may achieve similar imaging reading patterns for brain CT. This may mitigate queries regarding the influence of different backgrounds on training outcomes.

Comparison of clinical outcomes of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction.

BACKGROUND: Angiotensin receptor blockers (ARBs) are considered an alternative to angiotensin-converting enzyme inhibitors (ACEIs) in patients with acute myocardial infarction (AMI), but in the era of extensive use of preventive therapies and percutaneous coronary intervention, this has not been adequately evaluated in Asians. METHODS: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database. In total, 52,620 patients initially hospitalized due to AMI between 2002 and 2015 were assessed. RESULTS: After propensity score matching, 14,993 patients each were assigned to ACEI and ARB groups. Patients who received ARBs had significantly lower all-cause mortality (adjusted hazard ratio [aHR]: 0.82; 95% confidence interval [CI]: 0.75-0.90) and hospitalization for heart failure (aHR: 0.92; 95% CI: 0.85-0.99) compared with those who received ACEIs at 18 month follow-up. No significant difference was observed between the two groups in terms of major adverse cardiovascular events (aHR: 098; 95% CI: 0.90-1.07), cardiovascular death (aHR: 0.82; 95% CI: 0.68-1.00), ischemia stroke (aHR: 0.93; 95% CI: 0.77-1.11), and nonfatal myocardial infarction (aHR: 1.04; 95% CI: 0.93-1.17). ARBs showed benefits in many subgroups in terms of all-cause mortality and cardiovascular death. CONCLUSIONS: Real-world data demonstrate that ARBs might be associated with lower all-cause mortality and hospitalization for heart failure compared with ACEIs among patients with AMI.

Myasthenia gravis and independent risk factors for recurrent infection: a retrospective cohort study.

BACKGROUND: Approximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients. METHODS: This retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded. RESULTS: The recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent. CONCLUSIONS: The independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.

Toward controllable and predictable synthesis of high-entropy alloy nanocrystals.

High-entropy alloy (HEA) nanocrystals have attracted extensive attention in catalysis. However, there are no effective strategies for synthesizing them in a controllable and predictable manner. With quinary HEA nanocrystals made of platinum-group metals as an example, we demonstrate that their structures with spatial compositions can be predicted by quantitatively knowing the reduction kinetics of metal precursors and entropy of mixing in the nanocrystals under dropwise addition of the mixing five-metal precursor solution. The time to reach a steady state for each precursor plays a pivotal role in determining the structures of HEA nanocrystals with homogeneous alloy and core-shell features. Compared to the commercial platinum/carbon and phase-separated counterparts, the dendritic HEA nanocrystals with a defect-rich surface show substantial enhancement in catalytic activity and durability toward both hydrogen evolution and oxidation. This quantitative study will lead to a paradigm shift in the design of HEA nanocrystals, pushing away from the trial-and-error approach.

Evidence-based trends and association between symptom disturbance and physical activity among pregnant women: A longitudinal study.

BACKGROUND: Women usually decrease their physical activity (PA) after becoming pregnant. The change in PA may influence their symptom distress (SD). The changes and correlations between SD and PA throughout pregnancy remain unclear. AIMS: The aims of this study were to describe PA and SD trajectories across all three trimesters and examine their correlations during pregnancy. METHODS: A repeated-measure longitudinal study with convenience sampling at a hospital in Northern Taiwan was performed. Participants were recruited at 8-16 weeks of gestation, and two follow-up visits were performed at 24-28 weeks of gestation (second trimester) and after 36 weeks of gestation (third trimester). A total of 225 participants completed the study. The participants completed the Pregnancy Physical Activity Questionnaire (PPAQ) and Pregnancy-related Symptom Disturbance Scale (PSD), and sociodemographic and prenatal variables were recorded. RESULTS: Throughout pregnancy, SD decreased then increased, showing an overall upward trend, whereas PA showed the opposite pattern, increasing then decreasing, with an overall downward trend. Sedentary activity was positively correlated with both physical and psychological SD during the second and third trimesters. Exceeding the Institute of Medicine's recommendations for gestational weight gain, having childcare support, sport/exercise-type, and light-intensity PA were negatively associated with the physical and psychological SD, while a history of miscarriage and sedentary-intensity PA were positively associated with the physical and psychological SD. LINKING EVIDENCE TO ACTION: While several factors, including light-intensity PA, were found negatively associated with the physical and psychological SD, sedentary-intensity PA were positively associated with the physical and psychological SD, our findings shed light on future intervention strategies to relieve SD and decrease sedentary behavior among pregnant women.

Is the N2A Category Still Necessary for Oral Cancer Patients After Extranodal Extension Upgrade?

BACKGROUND: The presence of single-node metastasis (Ns) sometimes could be encountered in patients with oral squamous cell carcinoma (OSCC). The survival outcome for different Ns should be worthy of discussion. METHODS: Patients diagnosed with OSCC at the National Taiwan University Hospital between January 2007 and December 2018 were reviewed. All patients with Ns were classified into two groups: with and without extranodal extension (ENE). RESULTS: We analyzed 311 OSCC patients with Ns: 77 (24.76%) with and 234 (75.24%) without ENE. Lymph node (LN) >3 cm was the only significant factor associated with ENE (odds ratio 17.21, p < 0.001). The 5-year, disease-free survival of N1/N2A and N3B patients was 60.5% and 49.4%, respectively (p = 0.04), and the 5-year overall survival was 63.1% and 33.6%, respectively (p = 0.0001). Four fifths of Ns patients with LN >3 cm were upgraded to N3B category as ENE+. Postoperative radiotherapy (PORT) could provide significant benefit in regional control for Ns patients with (p = 0.03) and without (p = 0.0004) other adverse features. After multivariant Cox analysis, ENE+ was a modest and significant risk factor for disease-free (p = 0.08) and overall survival (p = 0.001). By contrast, the LN>3cm and N2A category were not significant risk factors for disease-free and overall survival. CONCLUSIONS: For OSCC patients with Ns, the survival outcome between N3B category and N1/N2A category was significantly different. After ENE+ upgrades (>80%), there were fewer N2A patients, and these patients became more comparable to N1 patients. PORT could significantly improve regional control for Ns patients.

Upregulation of APAF1 and CSF1R in Peripheral Blood Mononuclear Cells of Parkinson's Disease.

Increased oxidative stress and neuroinflammation play a crucial role in the pathogenesis of Parkinson's disease (PD). In this study, the expression levels of 52 genes related to oxidative stress and inflammation were measured in peripheral blood mononuclear cells of the discovery cohort including 48 PD patients and 25 healthy controls. Four genes, including ALDH1A, APAF1, CR1, and CSF1R, were found to be upregulated in PD patients. The expression patterns of these genes were validated in a second cohort of 101 PD patients and 61 healthy controls. The results confirmed the upregulation of APAF1 (PD: 0.34 ± 0.18, control: 0.26 ± 0.11, p < 0.001) and CSF1R (PD: 0.38 ± 0.12, control: 0.33 ± 0.10, p = 0.005) in PD patients. The expression level of APAF1 was correlated with the scores of the Unified Parkinson's Disease Rating Scale (UPDRS, r = 0.235, p = 0.018) and 39-item PD questionnaire (PDQ-39, r = 0.250, p = 0.012). The expression level of CSF1R was negatively correlated with the scores of the mini-mental status examination (MMSE, r = -0.200, p = 0.047) and Montréal Cognitive Assessment (MoCA, r = -0.226, p = 0.023). These results highly suggest that oxidative stress biomarkers in peripheral blood may be useful in monitoring the progression of motor disabilities and cognitive decline in PD patients.

Juvenile Myoclonic Epilepsy: Seizure and Social Outcomes in Taiwan.

Patients with juvenile myoclonic epilepsy (JME) may not achieve seizure freedom despite optimal treatment with antiseizure medications (ASMs). The aim of this study was to investigate the clinical and social features of patients with JME, and to determine the factors associated with outcomes. We retrospectively identified 49 patients with JME (25 females, mean age 27.6 ± 8.9 years) who were assessed at the Epilepsy Centre of Linkou Chang Gung Memorial Hospital in Taiwan. The patients were divided into two groups, those who were seizure-free and those with ongoing seizures according to their seizure outcome at the last follow-up for one year. Clinical features and social status were compared between these two groups. Twenty-four (49%) of the JME patients were seizure-free for at least one year, while 51% continued to experience seizures despite being treated with multiple ASMs. The presence of epileptiform discharges in the last electroencephalogram and seizures during sleep were significantly associated with worse seizure outcomes (p < 0.05). The patients who were seizure-free had a higher employment rate compared to those who continued to experience seizures (75% vs. 32%, p = 0.004). Despite receiving ASM treatment, a considerable proportion of the patients with JME continued to have seizures. Moreover, poor seizure control was associated with a lower employment rate, which may lead to negative socioeconomic consequences related to JME.

Association of Long-term Antiseizure Medication Use and Incident Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: Diabetes mellitus (DM) contributes significantly to metabolic syndrome and cardiovascular events, and it may be a comorbidity of epilepsy. The objective of this study was to investigate whether long-term antiseizure medication (ASM) use is associated with the risk of developing type 2 diabetes. METHODS: We analyzed data from the Chang Gung Research Database. Patients aged ≥45 years who received ASM treatment from January 2001 to May 2019 were identified. Patients with DM-associated diseases and short-term ASM use were excluded. The patients were classified into nonenzyme interaction, enzyme-inducing, enzyme-inhibiting, and mixed ASM groups. The rate of incident diabetes associated with individual ASM was further analyzed. Propensity score weighting was performed to balance between-group differences. Analyses were conducted with Cox proportional regression models and stabilized inverse probability of treatment weighting (IPTW). Hazard ratios (HRs) were calculated at 3, 4, 6, and 9 years after the index date and the end of follow-up. RESULTS: A total of 5,103 patients were analyzed, of whom 474 took nonenzyme interaction ASMs, 1,156 took enzyme-inducing ASMs, 336 took enzyme-inhibiting ASMs, and 3,137 took mixed ASMs. During follow-up (39,248 person-years), 663 patients developed new-onset DM, and the prevalence was 13.0%. The incidence of DM plateaued at 6-9 years after ASM initiation. Enzyme-inhibiting ASMs were significantly associated with a higher HR starting at the third year and then throughout the study period. The HRs were 1.93 (95% CI 1.33-2.80), 1.85 (95% CI 1.24-2.75), and 2.08 (95% CI 1.43-3.03) in unadjusted, adjusted, and stabilized IPTW models, respectively, at the end of follow-up. The dosing of ASM did not increase the risk of DM, and none of the individual ASM analyses reached statistical significance. DISCUSSION: The long-term use of enzyme-inhibiting ASMs was associated with an increased risk of incident DM, and the risk increased with the duration of treatment. These findings may guide the choice of drugs in those requiring long-term ASM therapy, particularly in high-risk individuals. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that enzyme-inhibiting ASMs were associated with an increased risk of developing DM compared with nonenzyme interaction ASMs.

Chemoprevention of oral cancer: A review and future perspectives.

BACKGROUND: Oral cancer causes significant morbidity and mortality. Chemoprevention utilizes medication or natural compounds to reverse oral premalignant lesions and to prevent second primary tumors. METHODS: A comprehensive PubMed database and Cochrane Library search from 1980 to 2021 was performed using the keywords "leukoplakia," "oral premalignant lesion," and "chemoprevention." RESULTS: Chemopreventive agents included retinoids, carotenoids, cyclooxygenase inhibitor, herbal extracts, bleomycin, tyrosine kinase inhibitors, metformin, and immune checkpoint inhibitors. Although some agents demonstrated effect in reducing premalignant lesions and preventing second primary tumors, the results among different studies were highly variable. CONCLUSIONS: The results of different trials, albeit inconsistent, provided substantial information for future studies. In the era of personalized medicine, future studies will focus on identifying specific biomarkers and molecular profile to monitor and to prevent malignant transformation. Larger trials are warranted to validate the effect of chemopreventive agents.