Smoking may increase the usage of antidepressant: evidence from genomic perspective analysis.

This study uses the two-sample Mendelian randomization (TSMR) method to explore the causal relationships between smoking initiation (SMKI), never smoking (NSMK), past tobacco smoking (PTSMK), and the usage of antidepressants (ATD). Single-nucleotide polymorphisms (SNPs) with genome-wide significance (P < 5E-08) related to SMKI, NSMK, and PTSMK were selected from the genome-wide association study (GWAS) database as instrumental variables (IVs). The main method, inverse variance weighted (IVW), was utilized to investigate the causal relationship. The results demonstrated a positive causal relationship between SMKI and ATD use, where SMKI leads to an increase in ATD use. Conversely, NSMK and PTSMK showed a negative causal relationship with ATD use, meaning that NSMK and PTSMK lead to a reduction in ATD use. Additionally, sensitivity analysis showed that the results of this study were robust and reliable. Using the TSMR method and from a genetic perspective, this study found that SMKI leads to an increase in ATD use, while NSMK and PTSMK reduce ATD use.

Analysis of antimicrobial drug usage in psychiatric specialized hospitals during the pandemic in China.

BACKGROUND: This study aims to compare antimicrobial drug usage in our hospital to Jiangsu Province and China from 2020 to 2022. RESEARCH DESIGN AND METHODS: A detailed analysis was performed using data from the National Antimicrobial Drug Clinical Application Monitoring Network. Several parameters were studied: the rate of antimicrobial drug use, number and types of drugs used, the rate of combined use, rate of microbiological examinations, drug use intensity, and cumulative Defined Daily Doses (DDDs). RESULTS: From 2020 to 2022, our hospital's antimicrobial drug usage rate was consistently lower than Jiangsu Province and China. The average number of drug types and the combined drug use rate were higher in 2020 but fell below those in Jiangsu Province and China in 2021 and 2022. Our microbiological examination rate consistently surpassed that of Jiangsu Province and China. Furthermore, our Antimicrobial Usage Density and cumulative DDDs were notably lower. While AUD remained stable, DDDs showed a decreasing trend. The most dominant drug in DDDs was cefditoren, a third-generation cephalosporin. CONCLUSIONS: During the pandemic years, our hospital not only met the requirements for antimicrobial drug usage, microbiological examination, AUD, and cumulative DDDs but also demonstrated a consistent year-by-year decrease in drug usage and DDDs.

Exploring adverse events of Vilazodone: evidence from the FAERS database.

OBJECTIVE: This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. METHODS: This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. RESULTS: The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). CONCLUSION: Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

Analysis of post-market adverse events of istradefylline: a real-world study base on FAERS database.

Analyze the adverse event (AE) signals of istradefylline based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS to calculate and evaluate the ratio and association between istradefylline and specific AEs. In the FAERS database, this study extracted data from the third quarter of 2019 to the first quarter of 2023, totaling 6,749,750 AE reports. After data cleansing and drug screening, a total of 3633 AE reports related to istradefylline were included for analysis. Based on four calculation methods, this study unearthed 25 System Organ Class (SOC) AE signals and 82 potential preferred terms (PTs) related to istradefylline. The analysis revealed new AEs during istradefylline treatment, including reports of Parkinsonism hyperpyrexia syndrome (n = 3, ROR 178.70, PRR 178.63, IC 1.97, EBGM 165.63), Compulsions (n = 5, ROR 130.12, PRR 130.04, IC 2.53, EBGM 123.02), Deep brain stimulation (n = 10, ROR 114.42, PRR 114.27, IC 3.33, EBGM 108.83), and Freezing phenomenon (n = 60, ROR 97.52, PRR 96.76, IC 5.21, EBGM 92.83). This study provides new risk signals and important insights into the use of istradefylline, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instructions.

Mining and analysis of security alert signals of valbenazine based on the Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Valbenazine is used for tardive movement disorders in adults. Current studies on its safety are mostly from clinical trials and small case reports, limiting information on rare adverse reactions. This study investigated valbenazine-related adverse event (AE) risk signals using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Valbenazine AEs data were collected from the FAERS database from 2017 Q2 to 2023 Q1, employing methods like reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. RESULTS: After data cleaning and drug screening, there were 20,837 AEs primarily suspecting valbenazine, involving 26 system organ classes and 125 AEs related to valbenazine at the preferred terms level. AEs related to valbenazine were mainly concentrated in nervous system disorders, general disorders and administration site conditions, and psychiatric disorders. Eye disorders and gastrointestinal disorders are new AEs not labeled in the valbenazine instructions. In addition, some new potential AE signals were found, such as Tardive dyskinesia and eyelid function disorder. CONCLUSION: The common AEs of valbenazine in the real world are consistent with the instructions, but there are some newly discovered suspicious AEs.

Unveiling potential adverse events associated with escitalopram oxalate: A real-world analysis based FDA adverse event reporting system database.

OBJECTIVE: The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. METHODS: This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. RESULTS: There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose (n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt (n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin (n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive (n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug's label. CONCLUSION: While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.

Multidimensional assessment of adverse events of bupropion: A large-scale data analysis from the FAERS database.

OBJECTIVE: Bupropion, a monocyclic antidepressant, aids in smoking cessation, treats major depression, and prevents severe depression in seasonal affective disorder patients. Yet, its adverse reactions remain insufficiently studied. METHODS: All data from the raw data packages for 78 quarters from the 1st quarter of 2004 to the 2nd quarter of 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database and imported into the SAS9.4 software for data cleaning and analysis. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods were used to analyze drug adverse events and assess their compliance with various screening criteria. RESULTS: The results showed a total of 36,862 reports related to Bupropion use, identifying 364 positive reaction terms (PT) covering 23 System Organ Classes (SOCs). In addition to known side effects, some new potential adverse reactions were found, such as Stool analysis abnormal, Oculocephalogyric reflex absent, Suspected suicide, and so on. At the same time, reactions like Encephalopathy neonatal, Hyponatraemic coma, and Electrocardiogram QRS complex prolonged were prominently ranked. Notably, occurrences such as Urine amphetamine positive and Amphetamines positive were relatively high, suggesting extra caution for these potential adverse reactions during clinical use of Bupropion. CONCLUSION: These findings highlight the potential health risks of long-term Bupropion use, especially concerning efficacy, positive drug tests, and suicidal tendencies. Therefore, it is recommended to monitor and assess patients using Bupropion more stringently to use this therapeutically potential drug more safely and effectively.

Design and application of a novel "turn-on" fluorescent probe for imaging sulfite in living cells and inflammation models.

Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.

Signal mining and risk analysis of Alprazolam adverse events based on the FAERS database.

This study aims to evaluate the safety of Alprazolam by analyzing the FAERS database, provide data analysis for monitoring adverse drug reactions. This research encompasses adverse event (AE) reports related to Alprazolam from the first quarter of 2004 to the second quarter of 2023. Four signal mining and analysis methods were utilized, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). Further exploration was conducted regarding patient characteristics and types of AEs. A total of 23,575 AE reports in which Alprazolam was the primary suspect drug were collected, identifying 347 Preferred Term (PT) signals and 27 System Organ Classes (SOCs). The number of AE reports increased annually, especially in 2015, 2018, 2019, and 2020. The main affected groups were females and the age range of 18 to 45. Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders were the most common the organ system in which the AEs occurred. There is a certain risk of drug abuse and suicide with Alprazolam. Most notably, several AEs not recorded in the Alprazolam leaflet appeared among the top 30 PTs in signal strength, including but not limited to Benzodiazepine drug level abnormal, Acquired amegakaryocytic thrombocytopenia, Cutaneous T-cell dyscrasia, and Coronary No-reflow Phenomenon. For the first time, AEs related to the cardiovascular system and platelet function were unveiled. The severe AE reports that resulted in "hospitalization" and "death" accounted for 30.96% and 21.86%. This study highlights the risks of suicide and misuse of Alprazolam. Other potential severe or fatal AEs, such as those related to the cardiovascular system, platelet function, and others, require further research to determine their precise mechanisms and risk factors.

Investigating the Mechanism of Chufan Yishen Formula in Treating Depression through Network Pharmacology and Experimental Verification.

Objective: To investigate the antidepressant effect and potential mechanism of the Chufan Yishen Formula (CFYS) through network pharmacology, molecular docking, and experimental verification. Methods: The active ingredients and their target genes of CFYS were identified through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and TCM-ID. We obtained the differentially expressed genes in patients with depression from the GEO database and screened out the genes intersecting with the target genes of CFYS to construct the PPI network. The key pathways were selected through STRING and KEGG. Then, molecular docking and experimental verification were performed. Results: A total of 113 effective components and 195 target genes were obtained. After intersecting the target genes with the differentially expressed genes in patients with depression, we obtained 37 differential target genes, among which HMOX1, VEGFA, etc., were the key genes. After enriching the differential target genes by KEGG, we found that the "chemical carcinogenesis-reactive oxygen species" pathway was the key pathway for the CFYS antidepressant effect. Besides, VEGFA might be a key marker for depression. Experimental verification found that CFYS could significantly improve the behavioral indicators of rats with depression models, including improving the antioxidant enzyme activity and increasing VEGFA levels. The results are consistent with the network pharmacology analysis. Conclusions: CFYS treatment for depression is a multicomponent, multitarget, and multipathway complex process, which may mainly exert an antidepressant effect by improving the neuron antioxidant stress response and regulating VEGFA levels.

Bacteria-Targeting Nanoparticles with ROS-Responsive Antibiotic Release to Eradicate Biofilms and Drug-Resistant Bacteria in Endophthalmitis.

Background: Bacterial endophthalmitis is an acute progressive visual threatening disease and one of the most important causes of blindness worldwide. Current treatments are unsatisfactory due to the emergence of drug-resistant bacteria and the formation of biofilm. Purpose: The aim of our research was to construct a novel nano-delivery system with better antimicrobial and antibiofilm effects. Methods: This study developed a novel antibiotic nanoparticle delivery system (MXF@UiO-UBI-PEGTK), which is composed of (i) moxifloxacin (MXF)-loaded UiO-66 nanoparticle as the core, (ii) bacteria-targeting peptide ubiquicidin (UBI29-41) immobilized on UiO-66, and (iii) ROS-responsive poly (ethylene glycol)-thioketal (PEG-TK) as the surface shell. Then the important properties of the newly developed delivery system, including biocompatibility, toxicity, release percentage, thermal stability, ability of targeting bacteria, and synergistic antibacterial effects on bacterial biofilms and endophthalmitis, were evaluated. Results: In vitro, MXF@UiO-UBI-PEGTK exhibited significant antibiotic effects including the excellent antibiofilm property against Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus at high levels of ROS. Moreover, MXF@UiO-UBI-PEGTK demonstrated outstanding efficacy in treating bacterial endophthalmitis in vivo. Conclusion: This novel nanoparticle delivery system with ROS-responsive and bacteria-targeted properties promotes the precise and effective release of drugs and has significant potential for clinical application of treating bacterial endophthalmitis.

BRG1 mediates epigenetic regulation of TNFα-induced CCL2 expression in oral tongue squamous cell carcinoma cells.

Strong evidence has indicated that upregulation of chemokine (CC motif) ligand-2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF-α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF-α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF-α-induced CCL2 transcription. Furthermore, we have observed that recruitment of NF-κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re-ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF-κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF-α stimulation. This process involves the cooperative action of acetylated histone and NF-κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF-α-induced CCL2 transcription in OTSCC cells.

Association between hypothyroidism subtypes and major depression: A two-sample Mendelian randomization study.

BACKGROUND: The causal relationship between different hypothyroidism subtypes and the risk of major depression (MD) is yet to be fully elucidated. This study aimed to determine if there's a causal relationship between various hypothyroidism subtypes (and related factors) and the risk of MD. METHODS: This genetic association study utilized a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between various hypothyroidism subtypes and MD risk. Genome-Wide Association Study (GWAS) summary statistics were obtained from the FinnGen and the UK Biobank. Instrumental variables (IVs) were chosen based on single nucleotide polymorphisms (SNPs). RESULTS: Among the analyzed hypothyroidism subtypes and related factors, "Hypothyroidism, strict autoimmune" (HTCBSA) and "Hypothyroidism, levothyroxin purchases" (HT/LP) demonstrated a statistically significant positive causal relationship with MD, with odds ratios of 1.020 (95 % CI: 1.004-1.037) and 1.022 (95 % CI: 1.005-1.040), respectively. The sensitivity analysis supported the robustness of these findings, showing no significant horizontal pleiotropy and confirming the stability of results when individual SNPs were removed. "Congenital iodine-deficiency syndrome/hypothyroidism" (CIDS/HT), "Postinfectious hypothyroidism" (PHT), "Hypothyroidism due to medicaments and other exogenous substances" (HDTDM and OES), "Thyroid Stimulating Hormone" (TSH), "Thyrotropin-releasing hormone" (THRH), and "Hypothyroidism, strict autoimmune, 3 medication purchases required" (HTCBSA/3MPR) showed no significant causal relationship with MD. LIMITATIONS: The study population was limited to individuals of European ancestry, and there may be certain genetic differences between different ethnic groups. CONCLUSIONS: This MR study suggests a potential causal relationship between certain hypothyroidism subtypes (specifically HTCBSA and HT/LP) and an increased risk of MD.

Causal relationship between diabetes and depression: A bidirectional Mendelian randomization study.

OBJECTIVE: This study explores the causal relationship between diabetes and depression using a two-sample Mendelian Randomization (TSMR) method. METHODS: The study selected single nucleotide polymorphisms (SNPs) closely associated with diabetes and depression in European populations from the Genome-Wide Association Study (GWAS) database, to serve as instrumental variables (IVs). The main evaluation method was inverse variance weighted analysis (IVW), supplemented by verification using Weighted median, Weighted mode, and MR Egger methods. The Odds Ratio (OR) and 95 % Confidence Interval (CI) were used as the main evaluation indicators, along with sensitivity analysis. RESULTS: This study found a negative correlation between diabetes and depression, suggesting that diabetes may reduce the risk of depression [IVW(FE): OR: 0.901, 95 % CI: 0.823 to 0.987; P = 0.025 < 0.05]. This finding was further confirmed by the Weighted median [OR: 0.844, 95 % CI: 0.730 to 0.974; P = 0.021 < 0.05] and Weighted mode method [OR: 0.766, 95 % CI: 0.637 to 0.921; P = 0.006 < 0.05]. However, the reverse showed no causal relationship between depression and diabetes (P > 0.05). Sensitivity analysis found no pleiotropy, and there were no large influences from individual SNPs on the result's robustness; the results are stable and reliable. CONCLUSION: For the first time, this study using TSMR analysis found a negative correlation between diabetes and the risk of depression onset in European populations, suggesting that diabetes might reduce the risk of depression. But as the mechanisms are still unclear, these findings warrant further study.

Mining and analysis of adverse event signals of Cariprazine based on the real-world data of FAERS database.

OBJECTIVE: This study aims to analyze the adverse events (AEs) of Cariprazine based on the FAERS database, providing evidence for its safety surveillance. METHODS: For signal quantification of Cariprazine-related AEs, we used disproportionality analysis including the Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) algorithms. RESULTS: We selected Cariprazine-related AE reports from the FAERS database from the fourth quarter of 2015 to the first quarter of 2023, and performed a detailed data analysis. Out of a total of 12,278,580 case reports, 3659 were found to be directly related to Cariprazine. We identified 140 Preferred Terms (PT) to describe these AEs, finding that they involved 27 organ systems. Specifically, AEs related to eye disorders such as Cataract cortical, Cataract nuclear, Accommodation disorder, Lenticular opacities, Oculogyric crisis, Dyschromatopsia were not explicitly mentioned in the drug's leaflet, indicating the presence of new ADR signals. CONCLUSION: Analysis of the FAERS database identified AEs associated with Cariprazine, notably in eye disorders not previously documented in the drug's official leaflet. These findings emphasize the need for continuous post-market surveillance and awareness among healthcare professionals regarding potential new ADR signals.

Incidence and influencing factors of post-stroke cognitive impairment in convalescent young patients with first-ever stroke.

OBJECTIVE: To investigate the occurrence of post-stroke cognitive impairment (PSCI) and its influencing factors in convalescent young patients with first-ever stroke. METHODS: A total of 300 first-ever young stroke patients (age ≤45 years) were collected. The Mini-Mental State Examination (MMSE) was used to assess the cognitive status. The sociodemographic data, clinical symptoms, social environment, and behavior-related information were collected and analyzed. RESULTS: The incidence of PSCI in young stroke patients was 62.33 %. Through univariate analysis, there were statistical differences in different levels of education, smoking status and hypertension (P < 0.05). With subsequently multivariate logistic regression analysis, it was found that junior high school (OR=8.58,95 %CI:2.25∼32.70) and high school (OR=10.50,95 %CI:2.69∼41.00) education levels, lesion volume >3.00 cm3 (OR=8.03,95 %CI:2.28∼28.36), stroke in the frontal-parietal-temporal region (OR=7.26,95 %CI:1.58∼33.40) and the basal ganglia area (OR=6.13,95 %CI:1.24∼30.43), high NIHSS score (OR=1.17,95 %CI: 1.06∼1.29), and high diastolic blood pressure variability coefficient (OR=1.43,95 %CI: 1.02∼2.01) were risk factors for PSCI. Meanwhile, 24≤BMI<28 (OR=0.06,95 %CI:0.02∼0.23) and BMI<24 (OR=0.18,95 %CI:0.06∼0.53), hospitalization cost >20,000/month (OR=0.22,95 %CI:0.09∼0.56), and stroke onset in spring and summer (OR=0.37,95 %CI:0.14∼0.96) were protective factors. CONCLUSION: The incidence of PSCI is relatively high in young stroke patients. Junior high and high school education, stroke lesions >3.00cm3, strokes in the frontal-parietal-temporal and basal ganglia regions, high NIHSS scores, and high DBPV are risk factors for PSCI in young stroke patients. Meanwhile, BMI<28, treatment cost >20,000/month, and stroke onset in spring and summer are protective factors for PSCI in young stroke patients.

Safety assessment of Brexpiprazole: Real-world adverse event analysis from the FAERS database.

OBJECTIVE: This study aims to analysis adverse drug events (ADE) related to Brexpiprazole from the third quarter of 2015 to the first quarter of 2023 from FAERS database. METHODS: The ADE data related to Brexpiprazole from 2015 Q3 to 2023 Q1 were collected. After standardizing the data, a variety of signal quantification techniques, including ROR, PRR, BCPNN, and MGPS were used for analysis. RESULTS: Among the 8559 ADE reports with Brexpiprazole as the primary suspected drug, 178 preferred terms (PT) of adverse reactions spanning 27 different system organ classes (SOC) were identified. Specifically, Metabolism and nutrition disorders and Reproductive system and breast disorders were unique adverse reactions to Brexpiprazole, with the latter not mentioned in the official drug label. Moreover, uncommon but significantly strong ADE signals, such as Egocentrism, Pharmacophobia, and Compulsions were observed. Notably, Tardive dyskinesia (n = 317, ROR 103.87, PRR 102.21, IC 6.21, EBGM 96.17) and Extrapyramidal disorder (n = 104, ROR 31.17, PRR 31.00, IC 4.57, EBGM 30.44) exhibited relatively high occurrence rates and signal strengths. Additionally, Lactation disorder (n = 6, ROR 48.09, PRR 48.07, IC 2.63, EBGM 46.71) and Breast discharge (n = 10, ROR 23.18, PRR 23.17, IC 2.94, EBGM 22.86) were observed, both presenting strong ADE signals. CONCLUSION: Brexpiprazole poses risks of various adverse reactions while providing therapeutic effects. In clinical applications, practitioners should closely monitor occurrences of Psychiatric disorders, Metabolism and nutrition disorders, Reproductive system and breast disorders, and other events.

The correlation of Esketamine with specific adverse events: a deep dive into the FAERS database.

Analyzing the vast data from FAERS database to evaluate the association between Esketamine and specific adverse events to guide clinical practice and regulatory decisions. Data related to Esketamine adverse events from 2019 Q1 to 2023 Q1 were collected from FAERS database. After data standardization, various signal quantification technologies, such as ROR, PRR, BCPNN, and MGPS, were employed to identify and evaluate adverse reaction signals closely related to the use of Esketamine comprehensively. A total of 5061 reports with Esketamine as the primary suspected drug were obtained, identifying 117 adverse reaction terms (PT) involving 27 system organ class (SOC) categories. Apart from the adverse events already mentioned in the drug's instructions, this study identified some new, clinically valuable potential AE signals, such as Flashback, Tachyphylaxis, and Autoscopy. In addition, high-ranking results included euphoric mood, feeling of relaxation, and feeling drunk. Notably, the occurrence frequencies of suicidal ideation and suicide attempt were relatively high, so clinicians should be particularly vigilant about these potential adverse reactions when using Esketamine. Moreover, since this drug is administered as a nasal spray, issues such as drug monitoring procedure incorrectly performed and nasal discomfort may arise. This study underscores the potential adverse reactions and risks of Esketamine in clinical applications, especially regarding long-term efficacy, addiction risks, and suicidal risks.

Relationship Between Sphingomyelin and Risk of Alzheimer's Disease: A Bidirectional Mendelian Randomization Study.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder whose etiology involves multiple genetic and environmental factors. Sphingomyelin (SM) is a type of sphingolipid found in cell membranes, and recent evidence suggests a potential link between SM and AD. However, the nature of this relationship remains unclear. Objective: To elucidate the potential causal relationship between SM levels and the risk of developing AD using a two-sample Mendelian randomization approach. Methods: The study utilized data extracted from the genome wide association study database. The primary analysis method was the inverse variance weighted (IVW) method, which was supplemented by weighted median, weighted mode, and MR Egger methods. The study specifically investigated the bidirectional causal relationship between SM and AD, evaluating odds ratios (OR) with a 95% confidence interval (95% CI). Results: Elevated levels of SM were found to be a risk factor for AD, as shown by IVW(MRE) [OR: 1.001, 95% CI: 1.000 to 1.002; p = 0.020 < 0.05], IVW(FE) [OR: 1.001, 95% CI: 1.001 to 1.002; p = 3.36e-07 < 0.05], and MR Egger. Conversely, AD was demonstrated to lead to an increase in SM levels [IVW(MRE): OR: 5.64e+08, 95% CI: 1.69e+05 to 1.89e+12; p = 1.14e-06 < 0.05], with consistent findings across the IVW(FE), MR Egger, weighted median, and weighted mode methods. Conclusions: The study establishes a bidirectional positive correlation between SM and AD. Increased SM levels are associated with a higher risk of developing AD, and the presence of AD can further elevate SM levels, potentially exacerbating the disease's progression.