Introduction: Pharmacotherapy with antiseizure medications (ASMs) has been a cornerstone for achieving long-term remissions in persons with epilepsy (PWEs). This study aims to determine the prescription patterns and treatment gaps (TGs) among PWEs. Methods: Accordingly, a descriptive cross-sectional study was conducted with 940 PWEs aged ≥18 years having clinically confirmed diagnosis of epilepsy based on the International League Against Epilepsy (ILAE) criteria. At a scheduled interview with each participant, a previously established questionnaire was used to obtain clinical information relating to epilepsy in terms of the age of onset, etiology, duration of epilepsy, frequency, types, and number of ASMs used. Results: There were fewer male participants [445 (47.4%) vs. 495 (53.6%)] than females, with a higher mean age of onset [(35.19 ± 21.10 vs. 31.58 ± 20.82 years; p = 0.009]. The medication characteristics showed that 336 (35.7%) of the 940 PWEs recruited were not on any ASMs, whereas the remaining 604 (64.3%) patients were on ASMs, with 504 (83.4%) on monotherapy vs. 100 (16.6%) on polytherapy. The PWEs on ASM monotherapy had a higher mean age [40.92 ± 19.40 vs. 33.61 ± 16.51 years; p < 0.001] and higher mean age of onset [34.47 ± 21.80 vs. 25.39 ± 19.78 years; p < 0.001] than those on polytherapy. Furthermore, there were more persons on ASM monotherapy among the participants with seizure duration < 2 years [251 (87.5%) vs. 36 (12.5%)] and seizure duration > 2 years [253 (79.8%) vs 64 (20.2%)]. Conclusion: The majority of the participants receiving ASMs were on monotherapy, with carbamazepine being the most frequently prescribed medication. Furthermore, about a third of the participants had TGs; therefore, healthcare providers should focus on alleviating the TGs among PWEs.

Chemotherapy is among the main classical approaches to the treatment of oncologic diseases. Its efficiency has been comprehensively proven by clinical examinations; however, the low selectivity of chemotherapeutic agents limits the possibilities of this method, making it necessary to search for new approaches to the therapy of oncologic diseases. Photodynamic therapy is the least invasive method and a very efficient alternative for the treatment of malignant tumors; however, its efficiency depends on the depth of light penetration into the tissue and on the degree of oxygenation of the treatment zone. In this work, a hitherto unknown conjugate of a natural bacteriochlorin derivative and doxorubicin was obtained. In vitro and in vivo studies showed a more pronounced activity of the conjugate against MCF-7 and 4T1 cells and its higher tumorotropicity in animal tumor-bearing animals compared to free anthracycline antibiotic. The suggested conjugate implements the advantages of photodynamic therapy and chemotherapy and has great potential in cancer treatment.

Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma-1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients ≥2 years old and as add-on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early-line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4-29 years old in whom up to 14 ASMs had previously failed, to illustrate real-world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug-drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well-tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS. PLAIN LANGUAGE SUMMARY: Fenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox-Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors\' everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine.

Extracellular vesicles (EVs) have great potential in oncology drug delivery because of their unique biological origin. Apoptotic bodies (ABs), as a member of the EV family, offer distinct advantages in terms of size, availability and membrane properties, but have been neglected for a long time. Here, using ABs and Ti2N nanosheets, we propose a novel drug delivery system (Ti2N-DOX@ABs), which exhibit a homologous targeting ability for dual-strategy tumor therapy with intrinsic biological property. The experimental results demonstrate that such a drug delivery system possesses a drug loading capacity of 496.5% and a near-infrared photothermal conversion efficiency of 38.4%. In addition, the investigation of drug internalization process proved that Ti2N-DOX@ABs featured a supreme biocompatibility. Finally, the dual-strategy response based on photothermal and chemotherapeutic effects was studied under near-infrared laser radiation. This work explores the opportunity of apoptosome membranes in nanomedicine systems, which provides a technical reference for cancer-oriented precision medicine research.

BACKGROUND: Treating tibial non-unions efficiently presents a challenge for orthopaedic trauma surgeons. The established gold standard involves implanting autologous bone graft with adequate fixation, but the addition of biologicals according to the so-called diamond concept has become increasingly popular in the treatment of non-unions. Previous studies have indicated that polytherapy, which involves implanting mesenchymal stem cells, bioactive factors and osteoconductive scaffolds, can improve bone healing. This study aims to evaluate the efficacy of polytherapy compared with monotherapy in treating tibial non-unions of varying severity.
METHODS: Data from consecutive tibial non-unions treated between November 2014 and July 2023 were retrospectively analysed. The Non Union Scoring System (NUSS) score before non-union surgery, and the Radiographic Union Score for Tibial fractures (RUST), scored at 1, 3, 6, 9, 12 and 18 months post-surgery, were recorded. Initially, a comparison was made between the polytherapy and monotherapy groups. Subsequently, patients receiving additional surgical non-union treatment were documented, and the frequency of these treatments was tallied for a subsequent per-treatment analysis.
RESULTS: A total of 34 patients were included and divided into a polytherapy group (n = 15) and a monotherapy group (n = 19). The polytherapy group demonstrated a higher NUSS score (44 (39, 52) versus 32 (29, 43), P = 0.019, z = -2.347) and a tendency towards a higher success rate (93% versus 68%, P = 0.104) compared with the monotherapy group. For the per-treatment analysis, 44 treatments were divided into the polytherapy per-treatment group (n = 20) and the monotherapy per-treatment group (n = 24). The polytherapy per-treatment group exhibited a higher NUSS score (48 (43, 60) versus 38 (30, 50), P = 0.030, z = -2.173) and a higher success rate (95% versus 58%, P = 0.006) than the monotherapy per-treatment group. Within the monotherapy per-treatment group, the NUSS score displayed excellent predictive performance (AUC = 0.9143). Setting the threshold value at 48, the sensitivity and specificity were 100.0% and 70.0%, respectively.
CONCLUSIONS: Polytherapy is more effective than monotherapy for severe tibial non-unions, offering a higher success ratio. The NUSS score supports decision-making in treating tibial non-unions.
METHODS: Level III.

In the landscape of paediatric epilepsy treatment, over 20 anti-seizure medications (ASMs) have gained approval from Drug Regulatory Agencies, each delineating clear indications. However, the complexity of managing drug-resistant epilepsy often necessitates the concurrent use of multiple medications. This therapeutic challenge highlights a notable gap: the absence of standardized guidelines, compelling clinicians to rely on empirical clinical experience when selecting combination therapies. This comprehensive review aims to explore current evidence elucidating the preferential utilization of specific ASMs or their combinations, with a primary emphasis on pharmacodynamic considerations. The fundamental objective underlying rational polytherapy is the strategic combination of medications, harnessing diverse mechanisms of action to optimize efficacy while mitigating shared side effects. Moreover, the intricate interplay between epilepsy and comorbidities partly may influence the treatment selection process. Despite advancements, unresolved queries persist, notably concerning the mechanisms underpinning drug resistance and the paradoxical exacerbation of seizures. By synthesizing existing evidence and addressing pertinent unresolved issues, this review aims to contribute to the evolving landscape of paediatric epilepsy treatment strategies, paving the way for more informed and efficacious therapeutic interventions.

Antihypertensive drug therapies have demonstrated their capacity to modulate the inflammatory processes associated with hypertension, leading to improvements in disease progression. Given the prevalent use of polytherapy in treating most hypertensive patients, comprehending the time-dependent effects of combination treatments on inflammation becomes imperative. In this study, spontaneously hypertensive rats (SHR) were divided into seven groups (n = 6): (i) SHR + vehicle, (ii) SHR + nebivolol, (iii) SHR + valsartan, (iv) SHR + lisinopril, (v) SHR + nebivolol-valsartan, (vi) SHR + nebivolol-lisinopril, and (vii) WKY + vehicle. Blood pressure was measured using the tail-cuff method. Temporal alterations in inflammatory cytokines TNF-α, IL-6, and IL-10 were assessed in serum through ELISA and mRNA expression in aortic tissue via qPCR after 1, 2, and 4 weeks of treatment with nebivolol, lisinopril, valsartan, and their respective combinations. Histological alterations in the aorta were assessed. The findings indicated that combined treatments reduced systolic and diastolic blood pressure in SHR. The nebivolol and lisinopril combination demonstrated a significant decrease in IL-6 serum and mRNA expression at both 1 week and 4 weeks into the treatment. Additionally, TNF-α mRNA expression also showed a reduction with this combination at the same time points. Particularly, nebivolol-valsartan significantly decreased TNF-α serum and mRNA expression after one and four weeks of treatment. Furthermore, an elevation in serum IL-10 levels was observed with both combination treatments starting from the second week onwards. This study provides compelling evidence that concurrent administration of nebivolol with lisinopril or valsartan exerts time-dependent effects, reducing proinflammatory cytokines TNF-α and IL-6 while modifying IL-10 levels in an experimental hypertensive model.

OBJECTIVE: The aim of this study was to investigate cranial magnetic resonance imaging (MRI) findings in different age groups and genders in pediatric epilepsy, to determine the percentages of etiologic factors, and to evaluate the association between MRI positivity and treatment resistance.
METHODS: Cranial MRIs of 359 patients with epilepsy aged 1 month to 18 years were retrospectively evaluated. Etiologic factors as an underlying cause of epilepsy were classified as previous parenchymal damage, hippocampal sclerosis, malformations of cortical development, tumor, neurocutaneous syndrome, myelination disorder, vascular anomaly, metabolic/genetic/neurodegenerative diseases, encephalitis, and an uncategorized \"other\" group. Data were transferred to IBM SPSS Statistics 25.0 (SPSS Inc., Chicago, IL, USA), and descriptive statistics, correlation analyses, chi-square, and t-tests were performed.
RESULTS: Among the patients included in the study, 141 (39.3%) had pathological findings on MRI related to the etiology. Previous parenchymal damage (39.7%) was the most common etiologic cause in all age groups. Regarding the relationship between drug resistance and MRI positivity, MRI positivity was observed in 72% of drug-resistant cases, while a complete response to therapy was found in 67.6% of MRI-negative cases.
CONCLUSIONS: MRI guides clinicians to determine the presence of an etiologic factor as the underlying cause of childhood epilepsy before treatment planning. MRI positivity is a remarkable indicator of response to antiseizure drug treatment and drug resistance.

OBJECTIVE: Many patients with epilepsy require polytherapy, which increases their antiseizure medication (ASM) drug load, a measure that considers the doses of all ASMs a patient is taking. Changes in concomitant ASM drug load after adding cenobamate were evaluated post-hoc in a subset of the open-label, phase 3 study.
METHODS: Patients 18-70 years old with uncontrolled focal seizures taking 1-3 ASMs were enrolled. Total concomitant ASM drug load (not including cenobamate) was calculated by dividing the patient\'s prescribed dose for each ASM by its defined daily dose, per the World Health Organization, then summing the ratios. Changes in concomitant ASM drug load were measured from baseline in 3-month intervals up to 24 months by both total and class-specific ASM drug load. Subgroups of interest included: older adults (65-70 years), prior epilepsy-related surgery vs none, and baseline seizure frequency < 3 vs ≥ 3 seizures/28 days.
RESULTS: Data from 240 patients were available (mean age 41.8 years, mean baseline drug load 3.57). Following cenobamate initiation, the mean concomitant ASM drug load was reduced by 29.4 % at Month 12 % and 31.8 % at Month 24. Reductions occurred in all assessed ASM drug classes, with the largest reduction in benzodiazepines (55.2 % at Month 24). Each assessed subgroup exceeded a 30 % reduction in concomitant ASM drug load at Month 24. Over 24 months, maintenance of ≥ 50 % response occurred in 89.3 %, 86.4 %, and 90.6 % of patients with low (-0.25 to <0), moderate (-0.59 to -0.25), or high (-3.3 to -0.59) numerical reductions in concomitant ASM drug load from baseline, respectively, compared with 86.0 % in patients with no change in drug load; maintenance of 100 % response occurred in 80.7 %, 84.3 %, and 70.0 % of patients with low, moderate, or high numerical reductions in concomitant ASM drug load, compared with 82.0 % in patients with no change.
CONCLUSIONS: Adding cenobamate led to reduced mean concomitant ASM drug loads during 1 and 2 years of treatment. Reductions occurred regardless of ASM drug class, patient age, or epilepsy disease characteristics and did not impact maintenance of response rates.

BACKGROUND: Drug-drug interactions (DDIs) represent an important clinical problem, particularly in older patients, due to polytherapy, comorbidity, and physiological changes in pharmacodynamic and pharmacokinetic pathways. In this study, we investigated the association between drugs prescribed after discharge from the hospital or clinic and the risk of DDIs with drugs used daily by each patient.
METHODS: We performed an observational, retrospective, multicenter study on the medical records of outpatients referred to general practitioners. DDIs were measured using the drug interaction probability scale. Potential drug interactions were evaluated by clinical pharmacologists (physicians) and neurologists. Collected data were analyzed using the Statistical Package for the Social Sciences.
RESULTS: During the study, we evaluated 1772 medical records. We recorded the development of DDIs in 10.3% of patients; 11.6% of these patients required hospitalization. Logistic regression showed an association among DDIs, sex, and the number of drugs used (p = 0.023).
CONCLUSIONS: This observational real-life study shows that the risk of DDIs is common in older patients. Physicians must pay more attention after hospital discharge, evaluating the treatment to reduce the risk of DDIs.