Device-related outcomes following hypoglossal nerve stimulator implantation.

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HGNS) has been widely used to treat obstructive sleep apnea in selected patients. Here we evaluate rates of revision and explant related to HGNS implantation and assess types of adverse events contributing to revision and explant. METHODS: Post-market surveillance data for HGNS implanted between January 1, 2018 and March 31, 2022, were collected. Event rates and risk were calculated using the post-market surveillance event counts and sales volume over the same period. Indications were categorized for analysis. Descriptive statistics were reported and freedom from explant or revision curves were grouped by year of implantation. RESULTS: Of the 20,881 HGNS implants assessed, rates of explant and revision within the first year were 0.723% and 1.542%, respectively. The most common indication for explant was infection (0.378%) and for revision was surgical correction (0.680%). Of the 5,820 devices with three-year post-implantation data, the rate of explant was 2.680% and of revision was 3.557%. During this same interval, elective removal (1.478%) was the most common indication, and for revisions, surgical correction (1.134%). CONCLUSIONS: The efficacy of HGNS is comparable in the real world setting to published clinical trial data. Rates of explant and revision are low, supporting a satisfactory safety profile for this technology.

Current practice and safety measures in epilepsy monitoring units in the Gulf Cooperation Council Countries: A cross-sectional study.

BACKGROUND: An increasing number of Epilepsy Monitoring Units (EMU) display various practices and safety protocols. EMU settings should meet clear, standardized safety protocols to avoid seizure adverse events (SAE). We aim to provide the foundational framework facilitating the establishment of unified evidence-based safety regulations to address the practices and safety measures implemented within the Gulf Cooperation Council (GCC). METHODS: In this cross-sectional study, EMU directors in the GCC were contacted directly by phone to personally complete an electronic 37-item questionnaire sent via text messages and email. From January 2021-December 2021. RESULTS: Seventeen EMUs from six GCC countries participated in the study. All EMU directors responded to the study. Twelve (70.6%) EMUs monitored adults and children, five (29.4%) monitored adults, and none monitored children only. The number of certified epileptologists in the EMUs ranged from one to eight per unit. Fifteen (88.2%) EMUs applied a continuous observation pattern, whereas two (11.8%) performed daytime only. The precautions most commonly used in the video Electroencephalogram (EEG) were seizure pads and bedside oxygen in 15 EMUs (88.2%). For invasive EEG, seizure pads were used in 9 EMUs (52.9%), %) and IV access in 8 EMUs (47.1%). The occurrence of adverse events varied among EMUs. The most common conditions were postictal psychosis 10 (58.8%), injuries 7 (41.2%), and status epilepticus 6 (35.3%). Falls were mainly related to missed seizures or delayed recognition by video monitors in 8 EMUs (47.1%). The extended EMU stay was because of an insufficient number of recorded seizures in 16 EMUs (94.1%), poor seizure lateralization and localization in 10 (58.8%), and re-introduction of AEDs in nine (52.9%). All EMUs had written acute seizure and status epilepticus management protocols. A postictal psychosis management protocol was available for 10 (58.8%). Medications were withdrawn before admission in 6 EMUs (35.3%). The specific medication withdrawal speed protocol upon admission was available in 7 EMUs (41.2%). Pre-admission withdrawal of medication demonstrated a shorter length of stay in both video and invasive EEG, which was statistically significant (ρ (15) = -.529, p =.029; ρ (7) = -.694, p =.038; respectively). CONCLUSION: The practice and safety regulations of EMUs in the GCC vary widely. Each EMU reported the occurrences of SAE and injuries. Precautions, protective measures, and management protocols must be reassessed to minimize the number of SAEs and increase the safety of the EMU.

Interactive exploration of adverse events and multimorbidity in CKD.

BACKGROUND AND HYPOTHESIS: Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality, and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study. METHODS: The GCKD study enrolled 5217 participants under regular nephrological care with an estimated glomerular filtration rate of 30-60 or >60 mL/min/1.73m2 and an overt proteinuria. Cardio-, cerebro- and peripheral vascular, kidney, infection, and cancer events, as well as deaths were adjudicated following a standard operation procedure. We summarized these time-to-event data points for exploration in interactive graphs within an R shiny app. Multivariable adjusted Cox models for time to first event were fitted. Cumulative incidence functions, Kaplan-Meier curves and intersection plots were used to display main adverse events and their combinations by sex and CKD etiology. RESULTS: Over a median of 6.5 years, 10 271 events occurred in total and 680 participants (13.0%) died while 2947 participants (56.5%) experienced any event. The new publicly available interactive platform enables readers to scrutinize adverse events and their combinations as well as mortality trends as a gateway to better understand multimorbidity in CKD: incident rates per 1000 patient-years varied by event type, CKD etiology, and baseline characteristics. Incidence rates for the most frequent events and their recurrence were 113.6 (cardiovascular), 75.0 (kidney), and 66.0 (infection). Participants with diabetic kidney disease and men were more prone to experiencing events. CONCLUSION: This comprehensive explorative tool to visualize adverse events (https://gckd.diz.uk-erlangen.de/), their combination, mortality, and multimorbidity among persons with CKD may manifest as a valuable resource for patient care, identification of high-risk groups, health services, and public health policy planning.

Post-Marketing Surveillance of the World's First Novel Cocktail of Rabies Monoclonal Antibodies: TwinRab™ in Real \-World Setting.

Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies.

COVID-19 vaccinations for patients with epilepsy in Guizhou Province, China: A cross-sectional study.

Several COVID-19 vaccines have been approved for emergency use according to China's immunization programs. These vaccines has created hope for patients with epilepsy, because the vaccines can help to reduce their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the COVID-19 vaccine safety in patients with epilepsy. Here, we assessed the time of symptom control and the features of adverse events of seizure patients following their COVID-19 vaccinations. The results showed that adverse events of COVID-19 vaccinations for epilepsy patients included local pain at the injection site, dizziness and headache, epileptic attack, somnolence, limb weakness, limb pain, allergy, and fever. In addition, the average recovery time of the adverse events was approximately 42 h. More importantly, our study showed that it was relatively safe to vaccinate epilepsy patients who did not experience seizures for approximately 12 months prior to the immunization date.

Recurrent pembrolizumab-induced mechanical small bowel obstruction in a patient with metastatic cervical cancer.

•Adverse events of pembrolizumab have been documented, but more severe gastrointestinal effects are not as well described.•We report a case of a patient with cervical cancer treated with pembrolizumab who developed small bowel obstruction (SBO)•Histological analysis and gastrointestinal workup points to pembrolizumab as likely cause of SBO.

Veliparib­Induced Toxicity in Cancer Patients: A Systematic Review and Meta­Analysis.

In this study, we investigate the veliparib­induced toxicity in cancer patients. Databases were searched for RCTs treated with veliparib. We found veliparib could increase the risk of hematologic and gastrointestinal toxicities. Anemia, neutropenia, thrombocytopenia, and nausea were the most common toxicities. Patients diagnosed with gastrointestinal tumors tend to have a higher risk of high-grade neutropenia; patients in the first-line setting tend to have a higher risk of high-grade anemia and neutropenia than those in the ≥ second line setting. Patients receiving higher dosage of veliparib tend to have a higher risk of all-grade anemia. Veliparib could also increase the risk of insomnia, myalgia, pneumonia, dyspnea, hyponatremia, and fatigue.

Achieving high inter-rater reliability in establishing data labels: a retrospective chart review study.

BACKGROUND: In medical research, the effectiveness of machine learning algorithms depends heavily on the accuracy of labeled data. This study aimed to assess inter-rater reliability (IRR) in a retrospective electronic medical chart review to create high quality labeled data on comorbidities and adverse events (AEs). METHODS: Six registered nurses with diverse clinical backgrounds reviewed patient charts, extracted data on 20 predefined comorbidities and 18 AEs. All reviewers underwent four iterative rounds of training aimed to enhance accuracy and foster consensus. Periodic monitoring was conducted at the beginning, middle, and end of the testing phase to ensure data quality. Weighted Kappa coefficients were calculated with their associated 95% confidence intervals (CIs). RESULTS: Seventy patient charts were reviewed. The overall agreement, measured by Conger's Kappa, was 0.80 (95% CI: 0.78-0.82). IRR scores remained consistently high (ranging from 0.70 to 0.87) throughout each phase. CONCLUSION: Our study suggests the detailed manual for chart review and structured training regimen resulted in a consistently high level of agreement among our reviewers during the chart review process. This establishes a robust foundation for generating high-quality labeled data, thereby enhancing the potential for developing accurate machine learning algorithms.

A disproportionality analysis of FDA adverse event reporting system (FAERS) events for ticagrelor.

Background: Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has not been fully elucidated. Method: We utilized OpenVigil 2.1 to query the FDA Adverse Event Reporting System database and retrieved reports by the generic name "ticagrelor" published between 1 October 2010 and 31 March 2023. Adverse drug events (ADEs) were classified and described according to the preferred terms and system organ classes in the Medical Dictionary of Regulatory Activity. Proportional reporting ratio (PRR), reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals. Results: The number of ADE reports with ticagrelor as the primary suspect drug was 12,909. The top three ADEs were dyspnea [1824 reports, ROR 7.34, PRR 6.45, information component (IC) 2.68], chest pain (458 reports, ROR 5.43, PRR 5.27, IC 2.39), and vascular stent thrombosis (406 reports, ROR 409.53, PRR 396.68, IC 8.02). The highest ROR, 630.24, was found for "vascular stent occlusion". Cardiac arrest (137 reports, ROR 3.41, PRR 3.39, IC 1.75), atrial fibrillation (99 reports, ROR 2.05, PRR 2.04, IC 1.03), asphyxia (101 reports, ROR 23.60, PRR 23.43, IC 4.51), and rhabdomyolysis (57 reports, ROR 2.75, PRR 2.75, IC 1.45) were suspected new adverse events of ticagrelor. Conclusion: The FAERS database produced potential signals associated with ticagrelor that have not been recorded in the package inserts, such as cardiac arrest, atrial fibrillation, asphyxia, and rhabdomyolysis. Further clinical surveillance is needed to quantify and validate potential hazards associated with ticagrelor-related adverse events.

Photobiomodulation in the treatment of palmar-plantar erythrodysesthesia: a randomised controlled clinical study protocol.

INTRODUCTION: Hand-foot syndrome, also known as palmar-plantar erythrodysesthesia (PPE), is a complication caused by chemotherapy. Clinically, it manifests as erythema and oedema on the palms of the hands and feet, dry and scaly skin, accompanied by a sensation of tightness and pain. Extreme cases have blisters and ulcerations that may require hospitalisation and/or pause in cancer treatment. It can also be accompanied by paraesthesia. Considering the characteristics, photobiomodulation (PBM) may reduce the PPE effects. The objective of this protocol will be to evaluate the efficacy of PBM in reducing PPE induced by capecitabine and 5-fluorouracil chemotherapy. METHODS AND ANALYSIS: This will be a randomised controlled, double-blind, double-centre clinical trial (Centro Asistencial del Sindicato Médico del Uruguay and Instituto Nacional del Cáncer from Uruguay). The sample population (40 individuals) will be divided into two groups: group 1 will receive moisturising cream plus PBM treatment and group 2 moisturising cream plus PBM sham treatment, at the ratio of 1:1. PBM will be performed at 630 nm two times per week in palmoplantar areas of the hands and feet (4 J/cm2), for 4 weeks. The PPE degree and the data referring to the chemotherapy treatment plan will be measured, prior to the start of treatment in the middle and at the end of it. Quality of life questionnaires will be applied at the beginning of the trial and at the end of treatment. The data will be analysed based on the intention-to-treat analysis and α<0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: The protocol was approved by the Research Ethics Committee of Universidad Católica del Uruguay (220316b), of Centro Asistencial del Sindicato Médico del Uruguay (221989) and of Instituto Nacional del Cáncer (2023-04). The recruitment has already started (March 2023). PROTOCOL VERSION: V.2, 27 October 2023. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05337423).

Risk of secondary immune thrombocytopenia following alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis.

Object: The purpose of this study was to evaluate the risk of secondary immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab through a meta-analysis. Methods: We searched databases including PubMed, Web of Science, OVID and EMBASE for studies reporting changes in platelet levels in MS patients treated with alemtuzumab from their inception until May 2023 and performed a meta-analysis. Information and data were screened and extracted by two researchers. The inclusion and exclusion criteria were established according to the PICOS principle. The obtained data were analyzed using the R software meta package and the quality assessment was conducted using Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger test. Results: A total of 15 studies were included, encompassing 1,729 multiple sclerosis patients. Meta-analysis of overall secondary ITP in the included studies yielded a pooled rate of 0.0243. The overall incidence of secondary autoimmune events was 0.2589. In addition, subgroup analysis was applied using study regions and study types. The results showed that the incidence rate of secondary ITP in Europe was about 0.0207, while the incidence of autoimmune events (AEs) was 0.2158. The incidence rate of secondary ITP and AEs in North America was significantly higher than in Europe, being 0.0352 and 0.2622. And the analysis showed that the incidence rates of secondary ITP and AEs in prospective studies were 0.0391 and 0.1771. Retrospective studies had an incidence rate of secondary ITP at 2.16, and an incidence rate of AEs at 0.2743. Conclusion: This study found that there was a certain incidence of Immune thrombocytopenia in multiple sclerosis patients after treatment with alemtuzumab. Alemtuzumab may have some interference with platelet levels, and the mechanism may be associated with Treg cells. But due to the absence of a control group in the included literature, we cannot determine the specific impact of Alemtuzumab on platelet levels in patients with MS. Therefore, clinical physicians should perform a comprehensive assessment of the patient's benefit-to-risk ratio before initiating alemtuzumab. Systematic Review Registration: Inplasy website, DOI number is 10.37766/inplasy2024.3.0007.

Radiotherapy plus temozolomide with or without anlotinib in H3K27M-mutant diffuse midline glioma: A retrospective cohort study.

BACKGROUND: Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly malignant brain tumor with dismal prognosis. Here, we intended to evaluate the efficacy and safety of a multitarget RTK inhibitor anlotinib in patients with H3K27M-DMG. METHODS: A total of 40 newly diagnosed H3K27M-DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed and compared. RESULTS: The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5-11.3) and 15.5 months (95% CI, 12.6-17.1), respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2-98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5-79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8-14.3) and 6.4 months (95% CI, 4.3-10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066-0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort. CONCLUSIONS: This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M-DMG. Further, anlotinib showed significant efficacy for H3K27M-DMG located in the infratentorial region.

Persistent Cytopenia After CD19 CAR T Therapy in Relapsed/Refractory DLBCL Patients Could Be a Predictor of Efficacy and Side Effects.

Hematological toxicity is a severe adverse event (AE) in anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the pathophysiological mechanism underlying prolonged cytopenia and the relationship between persistent cytopenia, efficacy, and AEs after anti-CD19 CAR T cell therapy are unknown. Therefore, this study explored whether persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs. Thirty-eight patients with R/R DLBCL were enrolled in an anti-CD19 CAR T cell therapy clinical trial. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR T cell therapy. The degree and duration of cytopenia, clinical response, proportion of CAR T cells, interleukin-6 (IL-6) levels, AEs, and follow-up were observed after therapy. Grades 3-4 persistent cytopenia occurred in 14 patients with R/R DLBCL, who recovered 8-18 weeks after CAR T cell infusion. These patients achieved an objective response rate (ORR) for anti-CD19 CAR T cell therapy. In patients who achieved ORR, the incidence of Grades 3-4 persistent cytopenia was higher in patients with a high tumor load than in those without a high tumor load. The mean peaks of IL-6 and anti-CD19 CAR T cells and the cytokine release syndrome grade in patients with Grades 3-4 persistent cytopenia were higher than those in patients without persistent cytopenia. Anti-CD19 CAR T cells were observed 21 and 28 days after infusion, and patients had Grades 3-4 persistent cytopenia. Progression-free and overall survival were higher in patients with Grades 3-4 persistent cytopenia than in those without cytopenia. Therefore, persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs, allowing clinicians to determine the efficiency of CD-19 CAR T cell therapy and the associated AEs.

Opportunistic CT for Prediction of Adverse Postoperative Events in Patients with Spinal Metastases.

The purpose of this study was to assess the value of body composition measures obtained from opportunistic abdominal computed tomography (CT) in order to predict hospital length of stay (LOS), 30-day postoperative complications, and reoperations in patients undergoing surgery for spinal metastases. 196 patients underwent CT of the abdomen within three months of surgery for spinal metastases. Automated body composition segmentation and quantifications of the cross-sectional areas (CSA) of abdominal visceral and subcutaneous adipose tissue and abdominal skeletal muscle was performed. From this, 31% (61) of patients had postoperative complications within 30 days, and 16% (31) of patients underwent reoperation. Lower muscle CSA was associated with increased postoperative complications within 30 days (OR [95% CI] = 0.99 [0.98-0.99], p = 0.03). Through multivariate analysis, it was found that lower muscle CSA was also associated with an increased postoperative complication rate after controlling for the albumin, ASIA score, previous systemic therapy, and thoracic metastases (OR [95% CI] = 0.99 [0.98-0.99], p = 0.047). LOS and reoperations were not associated with any body composition measures. Low muscle mass may serve as a biomarker for the prediction of complications in patients with spinal metastases. The routine assessment of muscle mass on opportunistic CTs may help to predict outcomes in these patients.

Exploration of Germline Correlates and Risk of Immune-Related Adverse Events in Advanced Cancer Patients Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of many tumor types, and durable responses can be observed in select populations. However, patients may exhibit significant immune-related adverse events (irAEs) that may lead to morbidity. There is limited information on whether the presence of specific germline mutations may highlight those at elevated risk of irAEs. We evaluated 117 patients with metastatic solid tumors or hematologic malignancies who underwent genomic analysis through the ongoing Personalized OncoGenomics (POG) program at BC Cancer and received an ICI during their treatment history. Charts were reviewed for irAEs. Whole genome sequencing of a fresh biopsy and matched normal specimens (blood) was performed at the time of POG enrollment. Notably, we found that MHC class I alleles in the HLA-B27 family, which have been previously associated with autoimmune conditions, were associated with grade 3 hepatitis and pneumonitis (q = 0.007) in patients treated with combination PD-1/PD-L1 and CTLA-4 inhibitors, and PD-1 inhibitors in combination with IDO-1 inhibitors. These data highlight that some patients may have a genetic predisposition to developing irAEs.

Unraveling the Complexities of Severe Acute Respiratory Syndrome Coronavirus 2: A Comprehensive Ophthalmic and Systemic Perspective.

The editorial explores the profound implications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, which emerged in December 2019 and rapidly evolved into a global health crisis. Despite initial focus on respiratory symptoms, the virus revealed significant ocular implications, prompting a reevaluation of the eye's role in its transmission, diagnosis, and systemic effects. The paradoxical nature of SARS-CoV-2-simultaneously novel and familiar within the coronavirus family-has been central to guiding the global medical response, including the swift development of vaccines. The pandemic has intensified research into the eye's susceptibility to viral infections, enhancing our understanding of virus-host interactions and the systemic impacts of viral diseases. The editorial delves into the pathophysiology of SARS-CoV-2, highlighting its potential to trigger autoinflammatory and autoimmune reactions with significant ocular repercussions. It examines the rapid vaccine development and deployment, the associated ocular side effects, and the ongoing research necessary to mitigate these outcomes. As the World Health Organization declared the end of COVID-19 as a public health emergency, the focus has shifted toward understanding the virus's long-term implications, including its effects on ocular health. This work underscores the critical role of interdisciplinary collaboration in addressing the systemic impacts of viral infections. It emphasizes the importance of ophthalmology in the broader context of public health and highlights the need for continued vigilance, research, and adaptation in a postpandemic world. The editorial calls for an integrated approach to health care, emphasizing the lessons learned from the SARS-CoV-2 pandemic to prepare for future health challenges, with a particular focus on the intersection of virology, immunology, and ophthalmology.

Rapid identification of inflammatory arthritis and associated adverse events following immune checkpoint therapy: a machine learning approach.

Introduction: Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors. Methods: We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs. Results: Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43). Discussion: Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.

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.

Impact of immunosuppressive agents on the management of immune-related adverse events of immune checkpoint blockers.

BACKGROUND: Immune checkpoint blockers (ICBs) can induce immune-related adverse events (irAEs) whose management is based on expert opinion and may require the prescription of steroids and/or immunosuppressants (ISs). Recent data suggest that these treatments can reduce the effectiveness of ICBs. OBJECTIVE: To investigate the relationship between the use of steroids and/or ISs and overall survival (OS) and progression-free survival (PFS) among ICB-treated patients with an irAE. METHODS: We prospectively collected data from the medical records of patients with solid tumors or lymphoma in the French REISAMIC cohort and who had been treated with ICBs between June 2014 and June 2020. RESULTS: 184 ICB-treated patients experienced at least one Common Terminology Criteria for Adverse Events grade ≥ 2 irAE. 107 (58.2%) were treated with steroids alone, 20 (10.9%) with steroids plus IS, 57 (31.0%) not received steroids or IS. The median OS was significantly shorter for patients treated with steroids alone (25.2 months [95% confidence interval (CI): 22.3-32.4] than for patients treated without steroids or IS (63 months [95%CI: 40.4-NA]) and those receiving an IS with steroids (53.4 months [95%CI: 47.3-NA]) (p < 0.001). The median PFS was significantly shorter for patients treated with steroids alone (17.0 months [95%CI: 11.7-22.9]) than for patients treated without steroids or IS (33.9 months [95%CI: 18.0-NA]) and those receiving an IS with steroids (41.1 months [95%CI: 26.2-NA]) (p = 0.006). There were no significant intergroup differences in the hospital admission and infection rates. CONCLUSION: In a prospective cohort of ICB-treated patients, the use of IS was not associated with worse OS or PFS, contrasting with the use of steroids for the management of irAEs.