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Epilepsy & Behavior Reports 2024Traumatic brain injury (TBI) patients are recommended to receive anti-seizure medication (ASM) as posttraumatic seizure (PTS) prophylaxis. However, the utilization of...
Traumatic brain injury (TBI) patients are recommended to receive anti-seizure medication (ASM) as posttraumatic seizure (PTS) prophylaxis. However, the utilization of ASM, including the prescription patterns and associated clinical characteristics, is limited in Taiwan. Thus, this study aimed to investigate the ASM trends and clinical characteristics. This retrospective cohort study enrolled TBI patients who received levetiracetam, phenytoin, and valproic acid during hospitalization using the National Health Insurance Research Database between 2012 and 2019. The primary outcome was the trend of the ASMs based on the index year. The duration of levetiracetam prescription was categorized as short-term (seven days or less) or long-term (more than seven days). Logistic regression identified the factors associated with long-term usage. A total of 64,461 TBI patients were included. Levetiracetam usage increased yearly, while phenytoin declined. Among the levetiracetam users, 5681 (30.38%) were short-term users, and 13,016 (69.62%) were long-term users. Diagnoses of contusions, intracranial hemorrhage, other intracranial injuries, receiving operations, and a history of cerebrovascular disease were significantly associated with longer duration. Conclusions This study revealed the rising trend of levetiracetam usage, indicating its potential as an alternative to phenytoin. TBI patients with more severe conditions were more likely to receive longer prescriptions.
PubMed: 38590545
DOI: 10.1016/j.ebr.2024.100662 -
International Journal of Biological... May 2024Frequent change of wound dressings introduces wound inflammation and infections. In this study, we electrospun phenytoin (PHT) loaded ethyl cellulose (EC) microfibers...
Frequent change of wound dressings introduces wound inflammation and infections. In this study, we electrospun phenytoin (PHT) loaded ethyl cellulose (EC) microfibers and solvent cast tetracycline hydrochloride (TCH) loaded carboxymethyl cellulose (CMC) films with the aim to demonstrate tailorable in vitro drug release behaviors suitable for long-term use of wound dressings. Results from tensile testing showed a significant decrease in average elastic moduli from 8.8 ± 0.6 to 3.3 ± 0.3 MPa after incorporating PHT into EC fibers. PHT-loaded EC fibers displayed a slow and zero-ordered release up to 80 % of the total drug at 48 h, while TCH-loaded CMC films demonstrated a rapid and complete release within 30 min. Furthermore, drug-loaded EC/CMC composites were fabricated into fiber-in-film and fiber-on-film composites. Fiber-in-film composites showed stage release of TCH and PHT at 8 h, while fiber-on-film composites demonstrated simultaneous release of PHT and TCH with a prolonged release of TCH from CMC films. In general, electrospun PHT-loaded EC microfibers, solvent cast TCH-loaded CMC films, and their composites were studied to provide a fundamental scientific understanding on the novelty of the ability to modulate drug release characteristics based on the composite designs.
Topics: Cellulose; Carboxymethylcellulose Sodium; Drug Liberation; Solvents; Phenytoin; Tetracycline; Tensile Strength
PubMed: 38582474
DOI: 10.1016/j.ijbiomac.2024.131374 -
Seminars in Neurology Jun 2024Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity. The treatment approach varies based on the... (Review)
Review
Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity. The treatment approach varies based on the time and the treatment stage of SE. Benzodiazepines are considered the first-line therapy during the emergent treatment phase of SE. Antiseizure medicines such as phenytoin, valproic acid, and levetiracetam are recommended during the urgent treatment phase. These drugs appear to have a similar safety and efficacy profile, and individualized therapy should be chosen based on patient characteristics. Midazolam, propofol, pentobarbital, and ketamine are continuous intravenous infusions of anesthetic medications utilized in the refractory SE (RSE) period. The most efficacious pharmacotherapeutic treatments for RSE and superrefractory status epilepticus are not clearly defined.
Topics: Status Epilepticus; Humans; Anticonvulsants
PubMed: 38580318
DOI: 10.1055/s-0044-1785503 -
Epilepsia Open Jun 2024Cenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the...
OBJECTIVE
Cenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the optimal cenobamate dose for maximal potential effectiveness while avoiding or minimizing drug-related adverse events (AEs), the administration of cenobamate with other ASMs must be managed through concomitant ASM load reduction. A panel of Spanish epilepsy experts aimed to provide a Spanish consensus on how to adjust the dose of concomitant ASMs in patients with drug-resistant epilepsy (DRE) in order to improve the effectiveness and tolerability of adjunctive cenobamate.
METHODS
A three-stage modified Delphi consensus process was undertaken, including six Spanish epileptologists with extensive experience using cenobamate. Based on current literature and their own expert opinion, the expert panel reached a consensus on when and how to adjust the dosage of concomitant ASMs during cenobamate titration.
RESULTS
The expert panel agreed that tailored titration and close follow-up are required to achieve the best efficacy and tolerability when initiating cenobamate in patients receiving concomitant ASMs. When concomitant clobazam, phenytoin, phenobarbital, and sodium channel blockers are taken at high dosages, or when the patient is receiving two or more sodium channel blockers, dosages should be proactively lowered during the cenobamate titration period. Other concomitant ASMs should be reduced only if the patient reports a moderate/severe AE at any stage of the titration period.
SIGNIFICANCE
Cenobamate is an effective ASM with a dose-dependent effect. To maximize effectiveness while maintaining the best tolerability profile, co-medication management is needed. The recommendations included herein provide practical guidance for proactive and reactive management of co-medication in cenobamate-treated patients with DRE and a high drug load.
PLAIN LANGUAGE SUMMARY
Patients with epilepsy may continue to have seizures even after treatment with several different antiseizure medications (ASMs). Cenobamate is an ASM that can reduce seizures in these patients. In this study, six Spanish experts in epilepsy discussed the best way to use cenobamate in drug-resistant epilepsy. They provide practical guidance on when and how the dose of other ASMs might be adjusted to reduce side effects and optimize the use of cenobamate.
Topics: Humans; Anticonvulsants; Carbamates; Drug Resistant Epilepsy; Spain; Drug Therapy, Combination; Chlorophenols; Consensus; Adult; Epilepsies, Partial; Seizures; Delphi Technique; Tetrazoles
PubMed: 38573131
DOI: 10.1002/epi4.12936 -
European Journal of Human Genetics :... Apr 2024By developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy, the Dutch Pharmacogenetics Working Group (DPWG) aims to advance the implementation...
By developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy, the Dutch Pharmacogenetics Working Group (DPWG) aims to advance the implementation of pharmacogenetics (PGx). This guideline outlines the gene-drug interaction of CYP2C9 and HLA-B with phenytoin, HLA-A and HLA-B with carbamazepine and HLA-B with oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9 intermediate and poor metabolisers, the DPWG recommends lowering the daily dose of phenytoin and adjust based on effect and serum concentration after 7-10 days. For HLA-B*15:02 carriers, the risk of severe cutaneous adverse events associated with phenytoin, carbamazepine, oxcarbazepine, and lamotrigine is strongly increased. For carbamazepine, this risk is also increased in HLA-B*15:11 and HLA-A*31:01 carriers. For HLA-B*15:02, HLA-B*15:11 and HLA-A*31:01 positive patients, the DPWG recommends choosing an alternative anti-epileptic drug. If not possible, it is recommended to advise the patient to report any rash while using carbamazepine, lamotrigine, oxcarbazepine or phenytoin immediately. Carbamazepine should not be used in an HLA-B*15:02 positive patient. DPWG considers CYP2C9 genotyping before the start of phenytoin "essential" for toxicity prevention. For patients with an ancestry in which the abovementioned HLA-alleles are prevalent, the DPWG considers HLA-B*15:02 genotyping before the start of carbamazepine, phenytoin, oxcarbazepine, and lamotrigine "beneficial", as well as genotyping for HLA-B*15:11 and HLA-A*31:01 before initiating carbamazepine.
PubMed: 38570725
DOI: 10.1038/s41431-024-01572-4 -
American Journal of Veterinary Research Jun 2024To assess the efficacy of transmucosal euthanasia solution to induce euthanasia.
OBJECTIVE
To assess the efficacy of transmucosal euthanasia solution to induce euthanasia.
ANIMALS
6 bearded dragons (Pogona vitticeps).
METHODS
An initial dose of euthanasia solution containing pentobarbital and phenytoin sodium was administered transmucosally in conscious lizards (100 mg/kg pentobarbital dose), followed by a second dose 20 minutes later (400 mg/kg pentobarbital dose). The presence of movement, leakage of euthanasia solution, behaviors consistent with oral irritation, respiratory rate, heart rate, palpebral and corneal reflex, and response to noxious stimuli were recorded until death, confirmed by the absence of Doppler cardiac flow and cardiac electrical activity. The time to loss of all parameters was calculated. Postmortem evaluation allowed for histopathologic evaluation of the oral cavity and gastrointestinal tract to detect potential mucosal damage from the alkaline euthanasia solution.
RESULTS
The median time to death was 300 minutes (range, 300 to 360 minutes), median time to respiratory arrest was 30 minutes (range, 30 to 50 minutes), and median time to loss of deep pain response was 30 minutes (range, 20 to 50 minutes). Signs consistent with oral irritation occurred in 4 of 6 (66.7%) lizards, including 2 lizards that exhibited whole-body spasms after euthanasia solution administration. Histopathologic changes indicating peracute mucosal ulceration, suspected to be from caustic causes, were identified in 1 (1/6 [16.7%]) lizard.
CLINICAL RELEVANCE
Transmucosal euthanasia solution administration resulted in clinical euthanasia within 6 hours. This method should be utilized only after premedication with analgesic and/or anesthetic medications due to the potential for acute mucosal ulceration and behaviors that may be distressing in client-owned animals.
Topics: Animals; Phenytoin; Lizards; Pentobarbital; Euthanasia, Animal; Male; Female; Administration, Mucosal; Hypnotics and Sedatives
PubMed: 38569538
DOI: 10.2460/ajvr.24.02.0026 -
Clinical Neurology and Neurosurgery May 2024Traumatic brain injury (TBI) and the subsequent Post-traumatic seizure (PTS) is a growing public health concern. Generally, anti-seizure drugs (ASDs) are recommended for... (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVE
Traumatic brain injury (TBI) and the subsequent Post-traumatic seizure (PTS) is a growing public health concern. Generally, anti-seizure drugs (ASDs) are recommended for PTS prophylaxis and treatment. This meta-analysis aimed to review the current state of knowledge and the evidence for the efficacy and safety of Levetiracetam (LEV) on the incidence of seizure in TBI patients compared to Phenytoin (PHT).
METHODS
A search was carried out based on PubMed, MEDLINE, Europe PMC database, and Cochrane Library up to November 2023. A total of 16 studies (3 randomized clinical trials, 10 retrospective cohort studies, and 3 prospective cohort studies) including 5821 TBI patients included in our meta-analysis. We included studies comparing LEV and PHT after brain injury in both adults and children. Risk of bias assessment was done for randomized controlled trials (RCTs) with a risk-of-bias tool (RoB-2) and the Newcastle-Ottawa Scale (NOS) was used to assess the quality of cohort studies. Two RCTs in our meta-analysis had a high risk of bias, therefore we applied sensitivity analysis to evaluate the robustness of our results.
RESULTS
The most commonly reported dosage for LEV was 500 mg twice daily and for PHT it was 5 mg/kg. There was no significant difference between LEV and PHT groups in reducing the early seizure incidence (OR = 0.85; 95% CI = [0.60, 1.21]; p = 0.375, fixed-effect, I = 21.75%). The result of sensitivity analysis for late seizure showed no significant difference between LEV and PHT in reducing the late seizure occurrence after TBI (OR = 0.87; 95% CI = [0.21, 3.67]; p = 0.853, fixed-effect, I = 0%). The mortality in TBI patients treated with LEV was not statistically significant compared to the PHT group (OR = 1.11; 95% CI = [0.92, 1.34], p = 0.266). The length of stay in the hospital was not significantly different between the LEV and PHT groups (MD = -1.33; 95% CI = [-4.55, 1.90]; p = 0.421). However, in comparison to PHT, LEV shortened the length of ICU stay (MD = -2.25; 95% CI = [-3.58, -0.91]; p =0.001). In terms of adverse effects, more patients in the PHT group have experienced adverse events compared to LEV but the difference was not significant (OR = 0.69; 95% CI = [0.44, 1.08]; p = 0. 11).
CONCLUSION
The results of our meta-analysis showed LEV and PHT have similar effects on the occurrence of early and late seizures in TBI patients. Therefore, none of the drugs is superior to the other in reducing PTS. However, treating TBI patients with LEV did not shorten the length of hospital stay in comparison to PHT but reduced the length of ICU stay significantly. The analysis showed that patients in the LEV experienced fewer side effects than in the PHT group, while it was not sufficiently clear whether all reported side effects were related to the drug alone or other factors. The mortality was similar between the LEV and PHT groups. Finally, we recommend more high-quality randomized controlled trials to confirm the current findings before making any recommendations in practice.
Topics: Humans; Anticonvulsants; Brain Injuries, Traumatic; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome
PubMed: 38569246
DOI: 10.1016/j.clineuro.2024.108251 -
Journal of Nanobiotechnology Apr 2024Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and...
Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation - hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.
Topics: Mice; Animals; Phenytoin; Administration, Intranasal; Tissue Distribution; Seizures; Epilepsy; Nanoparticles; Hydroxides
PubMed: 38566094
DOI: 10.1186/s12951-024-02405-8 -
Clinical Case Reports Apr 2024A high risk diabetic foot ulcer is treated by ozone therapy and collagen powder. The goal of this study was to report a high risk case, treated by ozone therapy, and...
KEY CLINICAL MESSAGE
A high risk diabetic foot ulcer is treated by ozone therapy and collagen powder. The goal of this study was to report a high risk case, treated by ozone therapy, and collagen powder. Ozone therapy and collagen powder can improve healing process of diabetic foot ulcers.
ABSTRACT
This case report presents a successful nonsurgical outpatient approach for managing a high-risk diabetic foot ulcer with tendon exposure in an older adult with uncontrolled diabetes mellitus and severe heart failure. Due to the patient's comorbidities, surgical intervention was not an option, leading to the utilization of ozone therapy, collagen powder, and Phenytoin ointment. The significance of this case lies in the treatment of a high-risk foot ulcer through a nonsurgical approach, considering the patient's uncontrolled diabetes and severe heart failure. Diabetic foot ulcers (DFUs) are debilitating and life-threatening complications, often resulting in amputations, socio-psychological burdens, and lifestyle changes. Conventional treatment methods have shown limited success, necessitating the exploration of new and innovative approaches. The use of ozone therapy has emerged as a potential treatment, but its safety and efficacy in DFUs require further investigation. The positive outcomes observed in this case report suggest that ozone therapy may be a viable option for treating DFUs, and further studies are recommended to evaluate its effectiveness.
PubMed: 38562577
DOI: 10.1002/ccr3.8728 -
Case Reports in Neurological Medicine 2024Adverse drug reactions to commonly prescribed medications such as phenytoin, used for seizures, often go undetected due to various factors. This case report highlights a...
Adverse drug reactions to commonly prescribed medications such as phenytoin, used for seizures, often go undetected due to various factors. This case report highlights a 52-year-old male diagnosed with late-onset epilepsy who was prescribed phenytoin. Despite the standard dosage, the patient experienced toxicity symptoms and a seizure, prompting admission for assessment. Laboratory tests and imaging were inconclusive, leading to a therapeutic drug monitoring (TDM) consultation, which revealed elevated phenytoin levels. Genetic testing for CYP2C9 polymorphisms was not feasible but noted as significant, especially in populations with higher prevalence. Phenytoin was tapered, leading to the patient's gradual recovery upon discontinuation and transition to valproate. The Naranjo scale predicted potential adverse drug responses (ADRs). This case underscores the significance of TDM, genetic considerations in drug metabolism, and the need to be vigilant in treating epilepsy to prevent such adverse events.
PubMed: 38560631
DOI: 10.1155/2024/2888895