ABSTRACT
Introduction Epilepsy is a complex prevalent seizure disorder impacting a significant number of individuals worldwide. Those with epilepsy face the possibility of experiencing sudden unexpected death in epilepsy (SUDEP). When examining the relationship between epilepsy and SUDEP, cardiac-related deaths (CRD) may be considered a driving force. We hypothesize that patients with epilepsy are at higher risk of CRD than those without epilepsy. While utilizing the National Institutes of Health (NIH) All of Us Researcher Program (AoU) database, we also explored the relationship between epilepsy and cardiac-related deaths and propose potential connective mechanisms between the two conditions. Methods Baseline data from the National Institutes of Health All of Us Researcher Program was used to evaluate the relationship between cardiac-related deaths and epilepsy. A retrospective cohort study was conducted where individuals with epilepsy and without epilepsy were matched by inclusion and exclusion criteria including death, cardiac-related death, and epilepsy. Additionally, the prevalence of cardiac-related deaths was compared to neurological, respiratory, and hepatic-related deaths for patients with epilepsy to identify emerging causes of SUDEP. Results Among patients with a history of epilepsy, the prevalence of CRD was 45 (17.3%) compared to 305 (11%) in the control group. This difference was statistically significant by p<0.0042 with an odds ratio (OR)=1.698, 95%CI 1.214-2.379. Additionally, there was the highest number of significant cardiac-related deaths amongst patients with epilepsy compared to patients without epilepsy as opposed to different mechanisms of death such as acute respiratory failure, acute hepatic failure, and hypoxic brain injury. Conclusion This study indicates that epileptic patients have a statistically significant higher prevalence of cardiac-related deaths. Additionally, cardiac-related deaths constitute a significantly higher proportion of fatalities amongst patients with epilepsy compared to other causes of SUDEP. Potential mechanisms for these findings may include seizure-induced arrhythmias, hypoxia-induced cardiac arrest, autonomic dysregulation, and neurotransmitter disequilibrium. The results of our study suggest promising directions for future research in identifying predictors of cardiac-related deaths with proposed cardiac monitoring protocols as preventative strategies for epileptic patients in efforts to reduce the prevalence of SUDEP.
ABSTRACT
Background: Hemophilus influenzae (H. influenzae) is a common cause of widespread bacterial infections and has been associated with the stabilization of the microbiome. The microbiome, through modulating systemic inflammation with possible upregulation of the NLRP3 inflammasome, may potentiate the development of breast cancer (BC). The purpose of this study was to therefore evaluate the correlation between previous H. influenzae infection and the incidence of BC. Methods: A large national database was used to collect International Classification of Disease Ninth and Tenth Codes to evaluate the incidence of BC between January 2010 and December 2019 in patients with and without H. influenzae history. A retrospective cohort study was performed where these groups of individuals were matched by age range, Charlson Comorbidity Index (CCI), and antibiotic treatment exposure. Significance and relative risk were obtained using standard statistical procedures. Results: A total of 13,599 patients were matched by age range and CCI in both the experimental and control groups. BC incidence was 259 (1.905%) in the H. influenzae group compared to 686 (5.044%) in the control group (P < 2.2 × 10-16; odds ratio (OR) = 0.604, 95% confidence interval (CI): 0.553 - 0.660). Matching by antibiotic treatment exposure resulted in two groups of 3,189 patients, in which BC incidence was 98 (3.073 %) in the H. influenzae group compared to 171 (5.362%) in the control group (P < 2.2 × 10-16; OR = 0.584, 95% CI: 0.515 - 0.661). Conclusion: The study shows a statistically significant correlation between H. influenzae and a reduced incidence of BC. These results warrant further research regarding H. influenzae's role in upregulating the NLRP3 inflammasome and its potential role in BC prevention and treatment.