Event Reports Research Articles

Analysis of Atypical Antipsychotics-Induced Adverse Events Related to Diabetes Mellitus in Patients With Dementia Using the Japanese Adverse Drug Event Report Database.

Patients with dementia are prescribed low-dose atypical antipsychotics (AAPs) to treat psycho-behavioral symptoms. Although AAPs are known to cause diabetes mellitus-related adverse events (DMAEs), information regarding AAPs-induced DMAEs experienced by patients with dementia is lacking. To use the Japan Adverse Drug Event Report (JADER) database to assess the onset tendencies and patterns of DMAEs attributable to AAPs prescribed to patients with dementia. We performed an analysis using dementia cases from the JADER database that were registered from April 2004 to December 2022. Data in the JADER database are completely anonymized; thus, we did not require institutional review board approval for using the JADER database in our study. The reporting odds ratio and proportional reporting ratio (PRR) were used to assess the onset tendencies of DMAEs with AAPs. In addition, Weibull shape parameters were used to assess the patterns of DMAEs that occur with the use of AAPs. We identified AAPs associated with DMAEs. In particular, low doses of quetiapine showed the potential to induce DMAEs. An analysis of the onset of DMAEs showed the early failure patterns for AAPs (median onset = 38 days). The AAPs may cause DMAEs in patients with dementia. Low doses of quetiapine may induce DMAEs. Health care workers should focus on the development of DMAEs during the early administration period of AAPs. These results may assist with the safe management of patients with dementia who use AAPs.

Model driven method for exploring individual and confounding effects in spontaneous adverse event reporting databases

ABSTRACT Background Spontaneous Adverse Event Reporting (SAER) databases play a crucial role in post-marketing drug surveillance. However, the traditional model-free disproportionality analysis has been challenged by the insufficiency in investigating subgroup and confounders. These issues result in significant low-precision and biases in data mining for SAER. Methods The Model-Driven Reporting Odds Ratio (MD-ROR) was proposed to bridge the gap between SAER database and explainable models for exploring individual and confounding effects. MD-ROR is grounded in a well-designed model, rather than a 2 × 2 cross table, for estimating AE-drug signals. Consequently, individual and confounding effects can be parameterized based on these models. We employed simulation data and the FDA Adverse Event Reporting System (FAERS) database. Result The simulated data indicated the subgroup effects estimated by MD-ROR were unbiased and efficient. Moreover, the adjusted-MD-ROR demonstrated greater robustness against confounding biases than the crude ROR. Applying our method to the FAERS database suggested higher occurrences of drug interactions and cardiac adverse events induced by Midazolam in females compared to males. Conclusion The study underscored that MD-ROR holds promise as a method for investigating individual and confounding effects in SAER databases.

Dental Disorders Reported to the FDA Adverse Event Reporting System in Association with Buprenorphine: An Analysis by Ingredient Composition and Route of Administration.

Prior research has suggested buprenorphine-containing medications may be associated with an increased risk of dental disorders. However, published data describing adverse dental reactions in buprenorphine users by active ingredient composition and route of administration are limited. The purpose of this study was to evaluate the influence of formulation on spontaneous reporting of dental disorders among patients treated with buprenorphine. Adverse event reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) between 2015 and 2022 were analyzed. Reporting odds ratios (ROR) and 95% confidence intervals (CI) were calculated to measure disproportionality of dental disorder reporting as classified by 39 Medical Dictionary for Regulatory Activities preferred terms. Compared to pooled reports for all other drugs across FAERS, both buprenorphine monotherapy (ROR 3.09; 95% CI 2.61-3.66) and combination buprenorphine/naloxone (ROR 14.61; 95% CI 13.34-16.01) were associated with positive disproportionality signals. Signals of disproportionate dental disorder reporting were also detected for buprenorphine medicines administered by sublingual (ROR 20.03; 95% CI 18.04-22.24), buccal (ROR 4.46; 95% CI 3.00-6.61) and oral (ROR 7.17; 95% CI 5.03-10.22) routes, but not for other modalities. In considering active ingredient and route together, sublingual buprenorphine monotherapies (ROR 23.55; 95% CI 17.84-31.11) and sublingual buprenorphine/naloxone (ROR 19.47; 95% CI 17.39-21.80) were each associated with disproportionate reporting of dental disorders. Subject to the limitations of spontaneous adverse event data, this study identified significantly disproportionate reporting of dental disorders to FAERS among patients treated with buprenorphine- containing medications, including formulations administered by sublingual, buccal and oral routes. These findings are consistent with prior data and suggest that regular oral care and proper dental hygiene be emphasized for patients undergoing therapy with orally dissolving buprenorphine.

Evaluating cardiac disorders associated with triazole antifungal agents based on the US Food and Drug Administration Adverse Event reporting system database.

Triazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased. The aim of this study was to analyze the cardiac disorders associated with TAAs (fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole) based on data from the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System. Data were extracted from the FAERS database between the first quarter of 2004 and third quarter of 2022. The clinical characteristics in TAA-associated cardiac AE reports were analyzed. Disproportionality analysis was performed to evaluate the potential association between AEs and TAAs using the reporting odds ratio (ROR) and proportional reporting ratio (PRR). Among 10,178,522 AE reports, 1719 reports were TAA-associated cardiac AEs as primary suspect drug. Most reports were related to fluconazole (38.34%), voriconazole (28.56%) and itraconazole (26.76%). Itraconazole (N = 195, 42.39%) and isavuconazole (N = 2, 14.29%) had fewer serious outcome events than three other drugs including fluconazole, voriconazole, and posaconazole. 13, 11, 26, 5 and 1 signals were detected for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. The number of new signals unrecorded in the drug label was 9, 2, 13, 2 and 0 for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. Isavuconazole might be the safest of the five TAAs for cardiac AEs. TAA-associated cardiac disorders may result in serious adverse outcomes. Therefore, in addition to AEs on the drug label, we should pay attention to new AEs unrecorded on the drug label during the clinical use of TAAs.

Study Partner Type and Adverse Event Reporting in Mild-to-Moderate Alzheimer's Disease Clinical Trials.

In randomized clinical trials (RCTs), monitoring adverse events (AEs) and serious AEs (SAEs) is critical. All Alzheimer's disease (AD) RCTs require participants to enroll with a study partner. We examined AE reporting rates in mild-to-moderate AD trials and their associations with study partner type. We estimated AE reporting rates using placebo data from seven independent RCTs conducted by the Alzheimer's Disease Cooperative Study. We assessed the heterogeneity of reporting rates as a function of visits using generalized estimating equations. In the primary analysis, we tested the hypotheses that the rates of reporting differed by study partner type and time they spent with the participant weekly using Poisson regression with robust variance estimation. In all regression models, log-transformed total patient years was included. The estimated reporting rates were 2.83 (95% CI: 2.66, 3.02), 1.18 (95% CI: 1.09, 1.28), 0.23 (95% CI: 0.19, 0.27), and 0.28 (95% CI: 0.24, 0.33) events per participant year for grade 1-3 AEs and SAEs, respectively. We estimated that greater number of visits per year was associated with increased reporting for grade 1-2 AEs and SAEs. We did not find evidence to suggest that AE reporting differed by study partner type or by time the study partner spent with the participant. Study partner type and time the study partner spent with the participant did not appear to impact AE reporting. Estimated reporting rates may be useful to evaluate safety in future studies, particularly those with no control arm and similar visit frequencies.

Analysis of drug-induced posterior reversible encephalopathy syndrome using the food and drug administration adverse drug events reporting system database

ABSTRACT Objective In this retrospective pharmacovigilance study, we gathered data on drug-induced posterior reversible encephalopathy syndrome (PRES). Our goal was to identify the primary suspect drugs in PRES by analyzing the Food and Drug Administration Adverse Events Reporting System (FAERS) database. Methods We identified and analyzed reports of PRES listed in the FAERS database between 2004 and 2021. Using the reporting odds ratio and 95% confidence interval, we evaluated the safety signals for each of the drugs associated with PRES. Results We reviewed 11,077 reports of adverse events corresponding to PRES. The primary suspect drug categories were antineoplastics, immunosuppressants, and glucocorticoids. PRES was 24.77% more likely to occur in females than in males. Drug-induced PRES usually occurs in individuals with cancer, those who have undergone an organ/stem cell transplant, and those with autoimmune conditions. Conclusion Our results show that the drugs most commonly suspected to cause PRES were antineoplastics, immunosuppressants, and glucocorticoids. Future studies are needed to illuminate the pathophysiological alterations that underlie PRES. In the meantime, prescribers and patients should be made aware of the potential risks of PRES associated with pharmaceutical therapy, and the summaries of product characteristics for individual drugs should be updated to include this information.

Modeled Hepatic/Plasma Exposures of Fluvastatin Prescribed Alone in Subjects with Impaired Cytochrome P450 2C9*3 as One of Possible Determinant Factors Likely Associated with Hepatic Toxicity Reported in a Japanese Adverse Event Database.

Fluvastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor that competitively inhibits human cytochrome P450 (P450) 2C9 in vitro. Drug interactions between a variety of P450 2C9 substrates/inhibitors and fluvastatin can increase the incidence of fluvastatin-related hepatic or skeletal muscle toxicity in vivo. In this survey, the prescribed dosage of fluvastatin was reduced or discontinued in 133 of 164 patients receiving fluvastatin alone, as recorded in the Japanese Adverse Drug Event Report database of spontaneously reported events. The median days to onset of fluvastatin-related disorders were in the range 30-35 d in the 87 patients. Therefore, we aimed to focus on fluvastatin and, using the pharmacokinetic modeling technique, estimated the virtual plasma and hepatic exposures in subjects harboring the impaired CYP2C9*3 allele. The plasma concentrations of fluvastatin modeled after a virtual oral 20-mg dose increased in homozygotes with CYP2C9*3; the area under the plasma concentration curve was 4.9-fold higher than that in Japanese homozygotes for wild-type CYP2C9*1. The modeled hepatic concentrations of fluvastatin in patients with CYP2C9*3/*3 after virtual daily 20-mg doses for 7 d were 31-fold higher than those in subjects with CYP2C9*1/*1. However, heterozygous Chinese patients with CYP2C9*1/*3 reportedly have a limited elevation (1.2-fold) in plasma maximum concentrations. Virtual hepatic/plasma exposures in subjects harboring the impaired CYP2C9*3 allele estimated using pharmacokinetic modeling indicate that such exposure could be a causal factor for hepatic disorders induced by fluvastatin prescribed alone in a manner similar to that for interactions with a variety of co-administered drugs.

A real-world pharmacovigilance study investigating the toxicities of histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors are emerging as promising treatments for hematological malignancies, with potential applications extending to solid tumors in the future. Given their wide-ranging biological effects, there is a pressing need for a thorough understanding of the toxicities linked to HDAC inhibition. In this study, a pharmacovigilance analysis was conducted using the FDA Adverse Event Reporting System database. Suspected adverse events linked to HDAC inhibitors were detected through various statistical methodologies, including reporting odds ratio, proportional reporting ratio, information component, and Empirical Bayes Geometric Mean. Our study findings have illuminated that, among the total reported cases examined, gastrointestinal disorders accounted for 13% patients of the cohort, while lymphatic system disorders comprised 8% cases of the cohort, all of which manifested as adverse events induced by HDAC inhibitors. Importantly, the usage of HDAC inhibitors was found to be associated with incidents of atrial fibrillation, heart failure, respiratory failure, hepatic dysfunction, and acute kidney injury. Romidepsin and belinostat demonstrated more pronounced signals of adverse events compared to panobinostat and vorinostat, emphasizing the need for vigilant monitoring of adverse events in this particular population. Furthermore, atrial fibrillation (clinical priority score of 7 points) emerged as the paramount medical event warranting utmost clinical attention. Eventually, multiple adverse events were observe to emerge within the initial and second months following the initiation of treatment. Vigilant monitoring and supportive care strategies are critical in addressing the toxicities associated with HDAC inhibitors, particularly those concerning cardiotoxicity, respiratory toxicity, renal toxicity, and hepatotoxicity.

The effect of parental bias on the reliability of children’s event reports and children’s memory for suggestive parental questioning.

The effect of parental bias on the reliability of children’s event reports and children’s memory for suggestive parental questioning.

Status of reports of adverse events related to botanical herbal medicines with toxic precautions officially managed by Korean government: A descriptive analysis from WHO VigiAccess

Objectives: This study was aimed to review the global status of adverse event (AE) reports and the characteristics of the reported AEs of plants managed as herbal medicines (HMs) with toxic precautions in Korea.Methods: This is a cross-sectional quantitative study that analyzed information available through VigiAccess, a website that provides summarized statistical information from the WHO's global AE database to the public. VigiAccess was searched in 8 Jan, 2024. Information on the total number of reports, number of reports by year and continent, and the age and gender of patients were obtained, and the types of frequently reported AEs were also reviewed.Results: Data on the status of report submissions were obtained for a total of 9 HMs including Aconitum ciliare, Aconitum carmichaeli, Arisaema japonicum, Pinellia ternata, Euphorbiae Lathyridis, Croton tiglium, Strychni Ignatii, Strychnons nux-vomica, and Linum usitatissimum. The number of reports per HM was from 1 to 137. The most commonly reported type of AEs were gastrointestinal disorders in most of the HMs, followed by neurological disorders. Serious adverse events were reported only in Strychni Ignatii, Strychnons nux-vomica, and Linum usitatissimum, including one case of death.Conclusions: This study shows the status of reported AEs of botanicals considered as HMs with toxic precautions in Korea based on real world data. However, when interpreting the findings of this study, readers should consider the significant limitations of this study mainly because of the characteristics of the data source.

Safety Profile of Paxlovid in the Treatment of COVID-19.

With the urgent and widespread application of Paxlovid, a novel antiviral drug for Coronavirus Disease 2019 (COVID-19) in clinical practice, concerns regarding its actual efficacy and safety have emerged. In order to provide more evidence to support its clinical application, we sought to perform a descriptive analysis of cases who experienced at least one Paxlovid-related adverse event (AEs) and reported to the FDA Adverse Event Reporting System (FAERS) in the post-marketing period. Individual adverse event reports between January 1, 2022 and September 30, 2022, were downloaded from the FAERS website. We completed a descriptive study about the safety of Paxlovid in the treatment of COVID-19. Further, we also analyzed the onset time of Paxlovid-related AEs. As of 30 September 2022, 16,529 de-duplicated cases were submitted to the FDA, and 5,860 (35.45%) were female. The average age was 58.38 years (S.D. 15.50). Most reports (12,390, 74.96%) were submitted by consumers and 1,436 (8.68%) concerned serious outcomes. The most frequently reported AEs were disease recurrence (7,724, 16.23%), dysgeusia (2,877, 6.05%), and diarrhoea (1,448, 3.04%). The median onset time of Paxlovid-related AEs was 8 days (interquartile range,1-10 days), and most of the cases (2,629, 19.12%) occurred on the day after Paxlovid initiation. This study indicates that the most common AEs reported with Paxlovid in post-marketing experience are consistent with the safety assessment of antiviral drugs. Even without emerging apparent safety concerns, the incidence of serious outcomes was unexpectedly high, and a few cases of potential new AEs occurred.

The Impact of the COVID-19 Pandemic on the Incidence of Herpes Zoster: A Narrative Literature Review.

Coronavirus disease 2019 (COVID-19) has had a broad impact on health services and health outcomes. During the pandemic, there were numerous reports of herpes zoster (HZ) in people with COVID-19 and in COVID-19 vaccine recipients. The aim of this review is to elucidate the global effects of the COVID-19 pandemic on HZ. It is postulated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces an immunosuppressive state that favours varicella zoster virus (VZV) reactivation. Three large cohort studies (a multinational study and studies from the USA and Spain) that excluded individuals vaccinated against HZ reported significantly increased risk of HZ following COVID-19 infection, especially in people aged ≥ 50years. In contrast, a large study from Israel that did not consider HZ vaccination status reported no such increase. Cases of HZ following COVID-19 vaccination have been reported and may be the result of attenuated cell-mediated immunity. This phenomenon appears to vary by vaccine type. Some (but not all) large analyses have reported a significant positive relationship between receipt of mRNA vaccines for COVID-19 and development of HZ. These include analyses of health records databases in Israel and Hong Kong and of spontaneous case reports in the US Vaccine Adverse Event Reporting System (VAERS) database. Routine vaccinations, including shingles vaccine programmes, were disrupted by the COVID-19 pandemic. It is estimated that missed shingles vaccinations may have resulted in 63,117 avoidable HZ cases in the USA. Now that the World Health Organization has declared an end to the COVID-19 pandemic as a health emergency and routine vaccination services have resumed, there is a need to increase awareness of HZ and HZ vaccination.Graphical abstract available for this article.

A real-world analysis of FDA Adverse Event Reporting System (FAERS) events for liposomal and conventional doxorubicins

The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.

Safety of Simultaneous Administration of Bivalent mRNA COVID-19 and Influenza Vaccines in the Vaccine Adverse Event Reporting System (VAERS).

Bivalent mRNA coronavirus disease 2019 (COVID-19) vaccines may be simultaneously administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. The aim was to describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. We searched the VAERS database for reports of adverse events (AEs) following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines during the period ofSeptember 1, 2022-March 31, 2023. We assessed the characteristics of these reports and described the most frequently reported AEs. Clinicians reviewed available medical records for reports of serious AEs and adverse events of special interest (AESI). During the period of1 September 2022 through 31 March 2023, VAERS received 3689 reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. The median age of vaccinees was 59 years (interquartile range 39, 70 years); 342 reports (9.3%) were classified as serious. The most common AEs among non-serious reports were severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2) infection (785, 23.5%), cough (592, 17.7%), and fatigue (568, 17.0%). The most common AEs among serious reports were Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (88, 25.7%), dyspnea (81, 23.7%), and condition aggravated (55, 16.1%). Reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusualorunexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19) was expected due to Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) reporting requirements. CDC and FDA will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines.

NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard): Concept and Launch event report

Background Vaccination is an important public health intervention, but not everyone benefits equally. Biological, social and structural factors render some communities vulnerable and unable to secure optimal health benefits from vaccination programmes. This drives health inequity and undermines wider vaccine impact by allowing the persistence of non-immune communities as foci for recurrent disease outbreaks. The NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard) aims to understand how biological, social, and structural factors interact to impair vaccine impact in vulnerable African communities. Methods The VAnguard project will be implemented through three thematic work packages (1-3) and four cross-cutting work packages (4-7). Work package 1 will investigate the biological drivers and mechanisms of population differences in vaccine responses. Work package 2 will support the understanding of how structural, social and biological determinants of vaccine response interrelate to determine vaccine impact. Work package 3 will synthesise data and lead analyses to develop, model and test community-based integrated strategies to optimise vaccine access, uptake and effectiveness. Work package 4 will plan and implement field investigations (community survey and qualitative studies (with support of work package 2) to explore structural, social & biological determinants impairing vaccine impact. Work package 5 will collaborate with work packages 1-4, to engage communities in designing interventions that aim to directly optimise vaccine impact through a process of co-learning and co-creation between them and the researchers. Work package 6 will build capacity for, and a culture of, consultative, collaborative multidisciplinary vaccine research in East Africa. Work package 7 will support the overall project management and governance. Following the project inception on the 1st of September 2022, project launch was held in November 2022. Conclusion Results from this project will contribute to the development of integrated strategies that will optimise vaccine benefits and drive health equity.

Safety Profile of Selective Serotonin Reuptake Inhibitors in Real-World Settings: A Pharmacovigilance Study Based on FDA Adverse Event Reporting System.

Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed agents to treat depression. Considering the growth in antidepressant prescription rates, SSRI-induced adverse events (AEs) need to be comprehensively clarified. This study was to investigate safety profiles and potential AEs associated with SSRIs using the Food and Drug Administration Adverse Event Reporting System (FAERS). A retrospective pharmacovigilance analysis was conducted using the FAERS database, with Open Vigil 2.1 used for data extraction. The study included cases from the marketing date of each SSRI (ie, citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) to April 30, 2023. We employed the reporting odds ratio and Bayesian confidence propagation neural network as analytical tools to assess the association between SSRIs and AEs. The Medical Dictionary for Regulatory Activities was used to standardize the definition of AEs. AE classification was achieved using system organ classes (SOCs). Overall, 427 655 AE reports were identified for the 6 SSRIs, primarily associated with 25 SOCs, including psychiatric, nervous system, congenital, familial, genetic, cardiac, and reproductive disorders. Notably, sertraline (n = 967) and fluvoxamine (n = 169) exhibited the highest and lowest signal frequencies, respectively. All SSRIs had relatively strong signals related to congenital, psychiatric, and nervous disorders. Most of our findings are consistent with those reported previously, but some AEs were not previously identified. However, AEs attributed to SSRIs remain ambiguous, warranting further validation. Applying data-mining methods to the FAERS database can provide additional insights that can assist in appropriately utilizing SSRIs.

Misinformation and the Vaccine Adverse Event Reporting System

This Viewpoint posits that to improve public understanding of the system, the Vaccine Adverse Event Reporting System (VAERS) could use a more accurate name, well-defined guidance about the reporting system’s nature and use, and comprehensible information about an event’s verification status.

Soft tissue injury events associated with neural integrity monitoring endotracheal tubes: A MAUDE database analysis

ObjectiveNeural integrity monitoring (NIM) endotracheal tubes are widely used to provide intraoperative monitoring of the recurrent laryngeal nerve during certain neck surgeries, especially thyroidectomy, in order to reduce the risk of nerve injury and subsequent vocal fold paralysis. The unique design of NIM tubes and the increased technical skill required for correct placement compared to standard endotracheal tubes may increase the risk of upper aerodigestive tract soft tissue injury. This study aims to describe adverse events related to NIM endotracheal tubes. Study designRetrospective cross-sectional study. SettingThe US Food and Drug Administration's MAUDE database (2010−2022); (Manufacturer and User Facility Device Experience). MethodsThe MAUDE database was queried for reports of adverse events that resulted in patient soft tissue injury involving the use of endotracheal tubes approved by the Food and Drug Administration. ResultsThere were 28 reported soft tissue injuries, with all events being related to the NIM EMG family of endotracheal tubes manufactured by Medtronic Xomed, Inc. Overall, 24 were categorized as device-related adverse events, and 4 were unspecified in the event description. The most common soft tissue injuries were edema (n = 7) and perforation (n = 7), each accounting for 25 % of adverse events. The second most common injury type was laceration (n = 4), representing 14 % of all adverse events. Overall, 9 patients (32 %) in our cohort required a surgical intervention to treat their injuries, which consisted of 6 tracheotomies and 3 instances of suture repair. ConclusionsThe most commonly reported types of soft tissue injury included edema and perforation, followed by laceration. Increased awareness of device-related patient injuries associated with NIM endotracheal tubes can be used to better inform surgeons and anesthesiologists during the process of intubation and surgical decision-making.

Adverse events associated with brolucizumab: a disproportionality analysis of the FDA adverse event reporting system (FAERS)

ABSTRACT Background The safety information of brolucizumab primarily comes from clinical trials experience. This study aimed to explore the ocular and systemic adverse events (AEs) associated with brolucizumab among real-world patients through data mining the FDA Adverse Event Reporting System (FAERS) database. Methods AE reports submitted to the FAERS database between October 2019 and March 2023 were extracted. The reporting odd ratio was used to evaluate AE signals associated with brolucizumab. Results There were 4,380,839 AE reports extracted from the FAERS database, 3,313 of which were with brolucizumab as primary suspected. A total of 150 ocular AE signals were identified. Ninety-nine were known ocular AEs listed in brolucizumab’ label, primarily including vision-related AEs, intraocular infections and retinal disorders. Fifty-one were unexpected ocular AE signals, including keratic precipitates, retinal perivascular sheathing, dry eye, glaucoma, etc. Meanwhile, several serious systemic AE signals, including arterial thromboembolic events and rhinorrhea, were also identified. Conclusions Several unexpected ocular and systemic AE signals associated with brolucizumab were identified through data mining of the FAERS database.

Adverse Drug Reactions prediction by combining wide & deep learning and POLY2

Accurate prediction of Adverse Drug Reactions (ADRs) holds immense importance in the field of clinical medicine and drug development. The requirement of accurate prediction spans various stages, ranging from drug design and clinical trials to marketing monitoring. The traditional ADR forecasting method has the disadvantage that it requires a lot of computing resources and is not suitable for large-scale forecasting. To address this issue, this study introduces the Wide & Deep model. This model combines the abilities of memorization and generalization to enhance the accuracy of ADR predictions. Additionally, we identify a shortcoming in the wide component of the traditional Wide & Deep model the lack of nonlinear transformation. Therefore, we propose the inclusion of POLY2 in the Wide & Deep model to rectify this shortcoming. By incorporating POLY2, our aim is to retain the models memorization and generalization abilities, leverage the nonlinear relationship between features, and capture the interaction effect between drug chemical substructures for better model performance. To validate our proposed method, we conduct experiments on two datasets: the FDA Adverse Event Reporting System (FAERS) and PubChem. The evaluation metric utilized is the Area Under the Curve (AUC) score, which demonstrates that our method outperforms the original model. The results indicate that by combining POLY2 feature crosses with the Wide & Deep model, we have achieved significant improvements in the prediction of ADRs.