Retrospective Multicenter Cohort Study on Safety and Electroencephalographic Response to Lacosamide for Neonatal Seizures.

BACKGROUND: There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates. METHODS: A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days. RESULTS: Among 47 neonates, 98% received the first lacosamide dose in the intensive care units. During the median follow-up of 12 days, 19% of neonates died, and the crude incidence rate per 1000 patient-days (95% confidence interval) of the adverse events by diagnostic categories ranged from 2.8 (0.3, 10.2) for blood or lymphatic system disorders and nervous system disorders to 10.5 (4.2, 21.6) for cardiac disorders. Electroencephalographic seizures were observed in 31 of 34 patients with available electroencephalographic data on the index date. There was seizure improvement in 29% of neonates on day 1 and also in 29% of neonates on day 2. On day 3, there was no change in 50% of neonates and unknown change in 50% of neonates. CONCLUSIONS: The results are reassuring regarding the safety of lacosamide in neonates. Although some neonates had fewer seizures after lacosamide administration, the lack of a comparator arm and reliance on qualitative statements in electroencephalographic reports limit the preliminary efficacy results.

Epidemiology of focal onset seizures in children aged >1 month to 4 years in Europe, United States, and Canada: A literature review.

The present study aims to report the currently available epidemiology of focal onset seizures in children aged >1 month to 4 years with the help of a literature review. The terms 'seizure*' OR 'epilepsy' combined with pediatric and epidemiology terms were used to search Embase, PubMed, and Web of Science up to November 16, 2021. Due to the scarcity of epidemiology data on focal onset seizures, the incidence and prevalence were estimated using the proportion of focal onset seizures in epilepsy patients from the most recently published articles. The estimated annual incidence per 100,000 children of focal onset seizures in children of 0-4 years of age ranged from 25.1 (95 % confidence interval [CI] 18.9-32.7) in the United Kingdom to 111.8 in the United States. The estimated period prevalence of focal onset seizures in children 0-4 years of age ranged from 0.15 % (99 % CI 0.13-0.18) in Canada to 0.61 % in the United States. Neurodevelopmental outcomes and psychiatric disorders were the most commonly reported comorbidities in children with epilepsy of age 0-4 years. Presence of focal onset seizures in children with different epilepsy syndromes needs to be thoroughly considered in the treatment planning of this population of interest.

Safety of intravenous lacosamide in hospitalized children and neonates.

OBJECTIVE: Seizures are common in critically ill children and neonates, and these patients would benefit from intravenous (IV) antiseizure medications with few adverse effects. We aimed to assess the safety profile of IV lacosamide (LCM) among children and neonates. METHODS: This retrospective multicenter cohort study examined the safety of IV LCM use in 686 children and 28 neonates who received care between January 2009 and February 2020. RESULTS: Adverse events (AEs) were attributed to LCM in only 1.5% (10 of 686) of children, including rash (n = 3, .4%), somnolence (n = 2, .3%), and bradycardia, prolonged QT interval, pancreatitis, vomiting, and nystagmus (n = 1, .1% each). There were no AEs attributed to LCM in the neonates. Across all 714 pediatric patients, treatment-emergent AEs occurring in >1% of patients included rash, bradycardia, somnolence, tachycardia, vomiting, feeling agitated, cardiac arrest, tachyarrhythmia, low blood pressure, hypertension, decreased appetite, diarrhea, delirium, and gait disturbance. There were no reports of PR interval prolongation or severe cutaneous adverse reactions. When comparing children who received a recommended versus a higher than recommended initial dose of IV LCM, there was a twofold increase in the risk of rash in the higher dose cohort (adjusted incidence rate ratio = 2.11, 95% confidence interval = 1.02-4.38). SIGNIFICANCE: This large observational study provides novel evidence demonstrating the tolerability of IV LCM in children and neonates.

A systematic review and meta-analyses on the prevalence of pregnancy outcomes in migraine treated patients: a contribution from the IMI2 ConcePTION project.

The present study aims to summarize the safety profile of the medications used to treat migraine during pregnancy by performing a systematic review and meta-analyses. The term "migrain*" combined with pregnancy terms were used to search Embase, PubMed, PsychInfo, Scopus, and Web of Science through 31 December 2020. Pooled prevalences of untreated and treated migraine patients were estimated using MetaXL software. Pooled odds ratios (OR) using random effects models were estimated in RevMan 5. All the identified studies assessed medications used to treat acute migraine. The pooled prevalence of adverse pregnancy outcomes in patients prescribed any migraine medication ranged from 0.4% (95% CI 0.2-0.7%) for stillbirth to 12.0% (95%CI 7.8-16.9%) for spontaneous abortions. Among untreated patients with migraine, the pooled prevalence of the assessed pregnancy outcomes ranged from 0.6% (95% CI: 0-1.7%) for stillbirth to 10.4% (95% CI: 8.9-12%) for gestational age < 37 weeks. Given the limited data, it was only possible to perform OR meta-analyses for triptans. The adjusted ORs for triptan users compared the general population were: for major malformations 1.07 (95%CI: 0.83-1.39, p = 0.60); birth weight < 2500g 1.18 (95%CI: 0.94-1.48, p = 0.16); gestational age < 37 weeks 1.49 (95% CI: 0.37-6.08, p = 0.58). In conclusion, triptans do not appear to increase the risk of pregnancy outcomes when compared to the general population. It was not possible to assess other migraine medications. Further studies are needed to investigate the safety of individual medications of acute and prophylactic migraine treatment among pregnant women.

Evaluation of Histologically and Histochemically Proven Cases of Vitiligo and its Correlation with CD4+ and CD8+ Lymphocyte Counts using Flow Cytometry.

INTRODUCTION: Vitiligo is an acquired cutaneous disorder characterized by progressive and selective destruction of melanocytes from the epidermis. Autoimmunity is strongly implicated in its pathogenesis. The destruction of melanocytes has a correlation with the peripheral blood lymphocyte imbalance mainly including Cytotoxic T cells (CD8+cells) and Helper T cells (CD4+cells). The progression of vitiligo is associated with higher CD8+ counts and lower CD4+ counts thus, altering CD4+: CD8+ ratio. AIM: To evaluate the clinically suspected cases of vitiligo histopathologically and histochemically and to establish the co-relation of autoimmunity with the flow cytometric analysis of CD8+ and CD4+ lymphocyte counts. MATERIALS AND METHODS: In this study, 40 patients with proven vitiligo were taken. The destruction of melanocytes was confirmed by Haematoxylin & Eosin (H & E) and by histochemical stains using Dihydroxyphenylacetic Acid (DOPA) reaction. Blood sample from these vitiligo patients and 10 control subjects was taken. Flow Cytometry was used for the determination of CD8+ and CD4+ counts in the vitiligo patients and control subjects. Then CD4+: CD8+ ratio was calculated and comparison between vitiligo patients and control subjects was done. T-test was used for the statistical analysis. RESULTS: There was statistically significant decrease in CD4+: CD8+ ratio. CD4+: CD8+ ratio was decreased in 57.5% cases of vitiligo with increase in CD8+ counts and decreased CD4+ counts. CONCLUSION: It was concluded from this study that cellular immunity might have a role to play in the pathogenesis of vitiligo causing the destruction of melanocytes.

Stage-specific survival and recurrence in patients with cutaneous malignant melanoma in Europe - a systematic review of the literature.

BACKGROUND: Given the increasing incidence in cutaneous malignant melanoma (CMM) and the recent changes in the treatment landscape, it is important to understand stage-specific overall and recurrence-free survival patterns in Europe. Despite publications such as EUROCARE-5, there is limited information on stage-specific survival for CMM in Europe. METHOD: We carried out a systematic literature review to provide an up-to-date summary of stage-specific survival and recurrence-free survival patterns in patients with CMM in Europe. Studies were included if they were published in Medline during the past 12 years and included information on stage-specific survival and/or recurrence in CMM. RESULTS: Of the 8,749 studies identified, 26 studies were included, representing nine countries. Collectively, the studies covered a population of 152,422 patients and included data from 1978 to 2011. Randomized clinical trials and single-center observational studies comprised the most common study designs, including five large registry-based studies. Stage-specific information for survival and recurrence varied: 5-year overall survival: 95%-100% (stage I), 65%-92.8% (stage II), 41%-71% (stage III), and 9%-28% (stage IV); 5-year relapse-free survival was reported less frequently: 56% (stage II), and 28%-44% (stage III). Studies reporting survival by sentinel node (SN) status reported 5-year overall survival as 80%-95% for negative SN (stage I/II) and 35%-75% for positive SN (stage III) status; recurrence-free survival at 5 years: 76%-90% for negative and 35%-58% for positive SN status. Some studies included comparisons of survival by key patient sociodemographic characteristics, suggesting that these have a substantial influence on survival and recurrence estimates. CONCLUSION: The studies identified in this review show large variations in stage-specific overall and recurrence-free survival by study type and by country. Owing to differing study designs and populations, it is difficult to make detailed comparisons. Large population-based studies that include stage-specific survival and recurrence in Europe are therefore important.

Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France.

PURPOSE: The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs), and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB-IV) or recurrent epithelial ovarian cancer (EOC). METHODS: A cross-sectional study was carried out in France with patients over 18 years, diagnosed with advanced (stage IIIB-IV) or recurrent EOC between 2009 and 2012. A total of 23 physicians (oncologists and gynecologists) participated, contributing 127 patients. Data were abstracted by participating physicians into a case report form. RESULTS: Of the 127 patients included, 92 (72.4%) had advanced EOC and 35 (27.6%) had recurrent EOC. A total of 73 comorbidities were reported in 44 patients (34.6%). Vascular (10.2%), metabolic (7.1%), respiratory (5.5%), and psychiatric disorders (5.5%) were the most common types of comorbidities reported. Prevalence of AEs was 74.8%, of which 12.6% were classified as serious. The most common AEs were anemia (16.5%), hematologic events (12.6%), taste change (11.8%), and headache (7.1%). Throughout the follow-up period, twelve patient deaths were reported (six due to disease progression). Of 35 patients with recurrent disease, 16 were highly platinum sensitive (recurrence >12 months after stopping platinum-based therapy), eleven were partially platinum sensitive (recurrence 6-12 months after stopping platinum-based therapy), seven were platinum resistant (recurrence within 6 months of stopping platinum-based therapy or progression while receiving second- or later-line platinum-based therapy), and one was platinum refractory (recurrence within 6 months from the start of first-line platinum-based therapy). CONCLUSION: In this cross-sectional study of advanced and metastatic ovarian cancer patients, approximately one-third of patients were diagnosed with comorbidities, and approximately three-quarters were diagnosed with AEs (12.6% with severe AEs).