In Vivo. 2024 Nov-Dec;38(6):2886-2896. doi: 10.21873/invivo.13770.

ABSTRACT

BACKGROUND/AIM: Immune-related adverse events (irAEs) occur in various organs, and sometimes multiply following treatment with immune checkpoint inhibitors (ICIs). This study aimed to determine the association between the number of irAEs and clinical outcomes.

PATIENTS AND METHODS: This was a retrospective study that included patients with lung cancer, melanoma, and head and neck cancer who were treated with anti-programmed cell death (ligand) 1 (PD-1/PD-L1) monotherapy. We evaluated the association between the number of irAEs and progression-free survival (PFS) in the simple Cox regression analysis. To eliminate the immortal-time bias, an additional landmark analysis was performed.

RESULTS: In total, 92, 69, and 37 patients were allocated to the no, single, and multisystem irAEs groups, respectively. The multisystem irAEs were associated with better PFS compared to the no irAE group. In contrast, at the 12-week landmark, multisystem irAEs were associated with poor PFS compared to the no irAEs group. Furthermore, the rate of treatment suspension owing to irAEs in the multisystem irAEs group (62.5%) was higher than that in the single irAE group (17.3%) at the 12-week landmark.

CONCLUSION: The incidence of multisystem irAEs was associated with improved clinical outcomes in patients with lung cancer, melanoma, and head and neck cancer treated with PD-1/PD-L1 inhibitor monotherapy. However, these results may be influenced by a potential immortal-time bias. When accounting for this bias, the early development of multisystem irAEs within 12 weeks was linked to treatment suspension and poorer clinical outcomes.

PMID:39477436 | DOI:10.21873/invivo.13770

J Nurs Adm. 2024 Nov 1;54(11):631-637. doi: 10.1097/NNA.0000000000001502. Epub 2024 Oct 11.

ABSTRACT

OBJECTIVE: The aim of this study was to analyze medication-related nursing medical malpractice cases to gain insights regarding how malpractice risk can be reduced.

BACKGROUND: The criminal prosecution and verdict of nurse RaDonda Vaught focused attention on the potential medicolegal risk for nurses related to medications.

METHODS: Medication-related medical malpractice cases involving nurses were obtained from a national database. Various attributes of these cases were examined, including contributing factors, injury severity, and case outcomes.

RESULTS: Authors identified 231 nursing medication-related medical malpractice cases closed from 2017 to 2021. The most frequent adverse events involved medication administration. Not following policies or protocols was the most common contributing factor. Opioids and epinephrine were the medications most frequently involved in the cases. Indemnity payments were made in 56.3% of the cases, with an average indemnity payment of $366 002.

CONCLUSIONS: Nursing medication-related medical malpractice cases are relatively uncommon, which may reassure nurses regarding medicolegal risk. Medications and contributing factors involved in the cases suggest patient safety interventions including education related to policies, procedures, and protocols.

PMID:39475893 | DOI:10.1097/NNA.0000000000001502

Br J Hosp Med (Lond). 2024 Oct 30;85(10):1-12. doi: 10.12968/hmed.2024.0388. Epub 2024 Oct 14.

ABSTRACT

Polypharmacy is common among older people and is associated with multiple adverse outcomes. Assessing whether it is appropriate or inappropriate for an individual is more informative than relying on a simple pill count. Modern medicine is based on single disease guidelines that promote prescribing but tend not to have deprescribing criteria. Barriers to deprescribing promote the accumulation of medicines over time. Clinical trial data have limitations due to the selected populations recruited. Some evidence suggests older people with multi-morbidity may benefit less and people with frailty are at increased risk of harm. Prescribing can be inappropriate if it is not evidence-based, harm is likely to exceed the benefit, includes hazardous medications or combinations of medicines, the patient experiences therapeutic burden, there is reduced adherence or prescribing cascades. Medicines optimisation aims to improve prescribing quality for an individual patient and may include deprescribing. It is a complex process that includes shared decision-making, careful follow-up, and communication of any resulting prescription changes.

PMID:39475037 | DOI:10.12968/hmed.2024.0388

Case Rep Dermatol. 2024 Oct 8;16(1):221-225. doi: 10.1159/000541046. eCollection 2024 Jan-Dec.

ABSTRACT

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, drug-induced adverse reaction characterized by skin eruptions, lymphadenopathy, fever, and a broad range of other bodily manifestations. The spectrum of histopathologic and clinical presentations is wide; therefore, DRESS syndrome can mimic other diseases.

CASE PRESENTATION: We present a case of a 4-year-old male patient who started chemotherapy with vincristine, cytarabine, and etoposide. The first clinical signs were fever, hemodynamic in-stability, and maculopapular erythema. Biopsies of skin lesions were taken, and hyperkeratosis, focal parakeratosis, acanthosis with slight spongiosis, and intraepithelial dyskeratotic cells were observed. There was a perivascular lymphoid infiltrate with abundant eosinophils in the dermis, and eosinophil permeations to the acrosyringium and epithelium were found.

CONCLUSION: DRESS syndrome is a drug-induced reaction that shares histopathological findings in skin biopsies with those seen in graft-versus-host disease. Although the histological findings are non-pathognomonic, they were characteristic enough to be of importance in the differential diagnosis.

PMID:39473560 | PMC:PMC11521526 | DOI:10.1159/000541046

Ann Med. 2024 Dec;56(1):2422573. doi: 10.1080/07853890.2024.2422573. Epub 2024 Oct 30.

ABSTRACT

BACKGROUND: Cutaneous adverse drug reactions (CADRs) remain a challenge for non-dermatologists. Medical-related applications to assist in learning about and managing patients with CADRs are scarce. We aimed to evaluate the efficacy of a web application for non-dermatologists in managing CADRs by comparing the knowledge scores of users and non-users.

MATERIALS AND METHODS: A multicenter randomized controlled trial was conducted between January 2023 and May 2023. Clinician participants were randomized (1:1) into the application and control groups using a simple randomization method. Knowledge scores between the groups were compared to evaluate the efficacy of the web application, and participants' perspectives on the application were also collected.

RESULTS: A total of 44 clinician participants were included in the final analysis. The median age was 33.0 years (95% confidence interval (CI) 27.5-35.0) and predominantly female (56.8%). The score in the application group (median, 27.0; 95% CI, 25.0-28.0) was significantly higher than that in the control group (median, 14.0; 95% CI 13.0-17.0) (p < 0.001). There were no differences in scores between the sex groups (p = 0.695), between general practitioners (GPs) and non-GPs (p = 0.93), or among groups with different frequencies of evaluation of patients with CADRs (p = 0.266). In addition, the participants in the application group rated a high level of overall satisfaction.

CONCLUSION: The web application for CADRs is an effective and convenient tool for assisting non-dermatologist physicians in learning and providing initial management with a high level of satisfaction. However, prospective long-term randomized controlled studies are required to confirm the efficacy of this tool.

PMID:39473307 | DOI:10.1080/07853890.2024.2422573

Sci Rep. 2024 Oct 29;14(1):25919. doi: 10.1038/s41598-024-75099-5.

ABSTRACT

While some literature has provided limited information about the potential cardiovascular risk and immune-related adverse events (irAEs) risk associated with PD-1/PD-L1 inhibitors in the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC), the exact relevance is still uncertain. To assess the pharmacovigilance (PV), constituent ratio, severity, and reaction outcomes of major adverse cardiovascular events (MACE) and immune-related adverse events (irAEs) related to PD-1/PD-L1 inhibitors for HNSCC reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed reports of cardiovascular adverse events and irAEs associated with drug therapy for HNSCC submitted to FAERS from the 1st quarter 2015 to the 3rd quarter of 2023. Three PD-1/PD-L1 inhibitors were identified: nivolumab, pembrolizumab and durvalumab. Our primary composite endpoint was the PV of MACE and irAEs related to PD-1/PD-L1 inhibitors in the treatment of HNSCC, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. 19,372 suspected drug-adverse event reports related to drug treatment in patients with HNSCC were identified, of which 916 reports were cardiovascular events, including 555 reports of MACE and 361 reports of other cardiovascular events. The PV signal regarding MACE was detected in durvalumab (PRR = 2.12, 95% CI: 1.24-3.61; χ2 = 7.71; ROR = 2.19, 95% CI: 1.24-3.86; IC = 1.01; IC025 = 0.07) but not in nivolumab and pembrolizumab. The constituent ratio of MACE in all adverse events caused by nivolumab (OR = 0.38, 95% CI: 0.19-0.73) and pembrolizumab (OR = 0.48, 95% CI: 0.23-0.99) was significantly decreased, compared with durvalumab. A PV signal about other cardiovascular events was detected in durvalumab (PRR = 3.04, 95% CI: 1.73-5.31; χ2 = 16.13; ROR = 3.15, 95% CI: 1.74-5.70; IC = 1.46; IC025 = 0.48), but it was not detected in nivolumab or pembrolizumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.25, 95% CI: 0.13-0.48) and pembrolizumab (OR = 0.40, 95% CI: 0.20-0.80) was significantly decreased, compared with durvalumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.61, 95% CI: 0.38-0.99) was significantly decreased, compared with pembrolizumab. There were 40 cases of hypertension. A PV signal about hypertension was detected in pembrolizumab (PRR = 3.72, 95% CI: 1.87-7.43; χ2 = 15.99; ROR = 3.75, 95% CI: 1.87-7.51; IC = 1.53, IC025 = 0.45), but it was not detected in nivolumab. The constituent ratio of hypertension in all adverse events caused by nivolumab (OR = 0.09, 95% CI: 0.09-0.39) was significantly decreased, compared with pembrolizumab. There were 737 cases of irAEs. A PV signal about irAEs was detected in nivolumab (PPR = 1.27, 95% CI: 1.05-1.53; χ2 = 6.38; ROR = 1.28, 95% CI: 1.06-1.56; IC = 0.29, IC025 = -0.00) and pembrolizumab (PPR = 2.20, 95% CI: 1.79-2.71; χ2 = 56.55; ROR = 2.31, 95% CI: 1.84-2.88; IC = 1.03; IC025 = 0.68), but it was not detected in durvalumab. The constituent ratio of irAEs in all adverse events caused by nivolumab (OR = 0.58, 95% CI: 0.44-0.76) significantly decreased, compared with pembrolizumab. By comparing the PV signals, constituent ratio, severity, and reaction outcome of the three drugs, we suppose that nivolumab can be used as the safest PD-1/PD-L1 inhibitor for HNSCC.

PMID:39472591 | DOI:10.1038/s41598-024-75099-5

In Vitro Cell Dev Biol Anim. 2024 Oct 29. doi: 10.1007/s11626-024-00978-0. Online ahead of print.

ABSTRACT

Infantile hemangiomas (IH) are a common entity encountered by dermatologists, otolaryngologists, and other surgeons. Oral propranolol is a mainstay of treatment for IH and is well-tolerated, though propranolol-refractory IH and other drug-related adverse events are documented and can limit its usage. There are few in vitro testing systems for putative treatment agents. To address this, we modified a tissue culture system for human hemangioma treatment testing to evaluate the treatment impact of the immune modifier, imiquimod. Human umbilical vein endothelial cells (HUVEC) and hemangioma cultures were treated with several concentrations of imiquimod followed by MTT assays, reporter gene assays, PCR, ELISA, and Western blotting for IL-8, VEGF, Cyclin D1, and IFNα and immunohistochemistry for Cyclin D1 and Ki-67. HUVEC showed acute decreases in IL-8, VEGF, and Cyclin D1 promoter activity and increases in IFNα mRNA after imiquimod treatment. Hemangioma samples showed no change in Ki-67 or Cyclin D1 staining after treatment with imiquimod after 27 d, with significantly increased IL-8 and VEGF. From this preliminary analysis, we discerned that hemangioma tissues can be grown in tissue culture and used for drug treatment studies. We also conclude acute and chronic modulation of cell cycle, angiogenesis factors, and immunostimulatory conditions may be associated with imiquimod mechanisms of action in hemangioma involution.

PMID:39472422 | DOI:10.1007/s11626-024-00978-0

Cochrane Database Syst Rev. 2024 Oct 29;10:CD012594. doi: 10.1002/14651858.CD012594.pub2.

ABSTRACT

BACKGROUND: Adverse drug events, encompassing both adverse drug reactions and medication errors, pose a significant threat to health, leading to illness and, in severe cases, death. Timely and voluntary reporting of adverse drug events by healthcare professionals plays a crucial role in mitigating the morbidity and mortality linked to unexpected reactions and improper medication usage.

OBJECTIVES: To assess the effectiveness of different interventions aimed at healthcare professionals to improve the reporting of adverse drug events.

SEARCH METHODS: We searched CENTRAL, Embase, MEDLINE and several other electronic databases and trials registers, including ClinicalTrials.gov and WHO ICTRP, from inception until 14 October 2022. We also screened reference lists in the included studies and relevant systematic reviews.

SELECTION CRITERIA: We included randomised trials, non-randomised controlled studies, controlled before-after studies, interrupted time series studies (ITS) and repeated measures studies, assessing the effect of any intervention aimed at healthcare professionals and designed to increase adverse drug event reporting. Eligible comparators were healthcare professionals' usual reporting practice or a different intervention or interventions designed to improve adverse drug event reporting rate. We excluded studies of interventions targeted at adverse event reporting following immunisation. Our primary outcome measures were the total number of adverse drug event reports (including both adverse drug reaction reports and medication error reports) and the number of false adverse drug event reports (encompassing both adverse drug reaction reports and medication error reports) submitted by healthcare professionals. Secondary outcomes were the number of serious, high-causality, unexpected or previously unknown, and new drug-related adverse drug event reports submitted by healthcare professionals. We used GRADE to assess the certainty of evidence.

DATA COLLECTION AND ANALYSIS: We followed standard methods recommended by Cochrane and the Cochrane Effective Practice and Organisation of Care (EPOC) Group. We extracted and reanalysed ITS study data and imputed treatment effect estimates (including standard errors or confidence intervals) for the randomised studies.

MAIN RESULTS: We included 15 studies (eight RCTs, six ITS, and one non-randomised cross-over study) with approximately 62,389 participants. All studies were conducted in high-income countries in large tertiary care hospitals. There was a high risk of performance bias in the controlled studies due to the nature of the interventions. None of the ITS studies had a control arm, so we could not be sure of the detected effects being independent of other changes. None of the studies reported on the number of false adverse drug event reports submitted. There is low-certainty evidence suggesting that an education session, together with reminder card and adverse drug reaction (ADR) report form, may substantially improve the rate of ADR reporting by healthcare professionals when compared to usual practice (i.e. spontaneous reporting with or without some training provided by regional pharmacosurveillance units). These educational interventions increased the number of ADR reports in total (RR 3.00, 95% CI 1.53 to 5.90; 5 studies, 21,655 participants), serious ADR reports (RR 3.30, 95% CI 1.51 to 7.21; 5 studies, 21,655 participants), high-causality ADR reports (RR 2.48, 95% CI 1.11 to 5.57; 5 studies, 21,655 participants), unexpected ADR reports (RR 4.72, 95% CI 1.75 to 12.76; 4 studies, 15,085 participants) and new drug-related ADR reports (RR 8.68, 95% CI 3.40 to 22.13; 2 studies, 7884 participants). Additionally, low-certainty evidence suggests that, compared to usual practice (i.e. spontaneous reporting), making it easier to report ADRs by using a standardised discharge form with added ADR items may slightly improve the total number of ADR reports submitted (RR 2.06, 95% CI 1.11 to 3.83; 1 study, 5967 participants). The discharge form tested was based on the 'Diagnosis Related Groups' (DRG) system for recording patient diagnoses, and the medical and surgical procedures received during their hospital stay. Due to very low-certainty evidence, we do not know if the following interventions have any effect on the total number of adverse drug event reports (including both ADR and ME reports) submitted by healthcare professionals: - sending informational letters or emails to GPs and nurses; - multifaceted interventions, including financial and non-financial incentives, fines, education and reminder cards; - implementing government regulations together with financial incentives; - including ADR report forms in quarterly bulletins and prescription pads; - providing a hyperlink to the reporting form in hospitals' electronic patient records; - improving the reporting method by re-engineering a web-based electronic error reporting system; - the presence of a clinical pharmacist in a hospital setting actively identifying adverse drug events and advocating for the identification and reporting of adverse drug events.

AUTHORS' CONCLUSIONS: Compared to usual practice (i.e. spontaneous reporting with or without some training from regional pharmacosurveillance units), low-certainty evidence suggests that the number of ADR reports submitted may substantially increase following an education session, paired with reminder card and ADR report form, and may slightly increase with the use of a standardised discharge form method that makes it easier for healthcare professionals to report ADRs. The evidence for other interventions identified in this review, such as informational letters or emails and financial incentives, is uncertain. Future studies need to assess the benefits (increase in the number of adverse drug event reports) and harms (increase in the number of false adverse drug event reports) of any intervention designed to improve healthcare professionals' reporting of adverse drug events. Interventions to increase the number of submitted adverse drug event reports that are suitable for use in low- and middle-income countries should be developed and rigorously evaluated.

PMID:39470185 | DOI:10.1002/14651858.CD012594.pub2

J Hepatocell Carcinoma. 2024 Oct 24;11:2033-2047. doi: 10.2147/JHC.S481410. eCollection 2024.

ABSTRACT

PURPOSE: To evaluate safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics, of fostroxacitabine bralpamide (fostrox, MIV-818), a novel oral troxacitabine nucleotide prodrug designed to direct exposure to the liver, while minimizing systemic toxicity.

PATIENTS AND METHODS: Fostrox monotherapy was administered in an open-label, single-arm, first-in-human, phase 1a/1b study, in patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or solid tumor liver metastases. The first part (1a) consisted of intra/inter-patient escalating doses (3 mg to 70 mg) QD for up to 5 days, and the second part (1b), doses of 40 mg QD for 5 days, in 21-day cycles. Safety and tolerability were evaluated by the Safety Review Committee, and efficacy was assessed every 6 weeks with CT or MRI using RECIST 1.1 and mRECIST.

RESULTS: Nineteen patients were treated with fostrox. Most common adverse events (AEs) were hematological and increased AST. Grade 3 treatment related AEs (TRAE) were seen in 53% of the patients, with transient neutropenia and thrombocytopenia as the most common. No grade 5 AE was observed. Recommended Phase 2 dose of fostrox was 40 mg QD for 5 days in 21-day cycles. Preliminary efficacy showed a clinical benefit rate in the liver of 53% and stable disease (SD) as best response in 10 patients. Liver targeting with fostrox was confirmed with higher exposure of troxacitabine and its metabolites in liver compared to plasma. Systemic exposure of fostrox was generally low with troxacitabine as main analyte. Biopsies demonstrated tumor-selective, drug-induced DNA damage.

CONCLUSION: The phase 1a/1b monotherapy study of fostrox, in patients with liver tumors, showed a tumor selective effect in the liver and that 40 mg QD for 5 days in 21-day cycles is safe and tolerable. Safety and preliminary efficacy in patients with advanced HCC supports clinical development of fostrox in combination with other modes of action in HCC.

PMID:39469286 | PMC:PMC11514655 | DOI:10.2147/JHC.S481410

J Korean Med Sci. 2024 Oct 28;39(41):e270. doi: 10.3346/jkms.2024.39.e270.

ABSTRACT

BACKGROUND: There is a dearth of research on the factors linked with adverse events (AEs) associated with nirmatrelvir/ritonavir (NMVr) and molnupiravir (MOL), particularly in the elderly. Therefore, this study aimed to investigate self-reported AEs and identify factors associated with the occurrence of AEs following NMVr or MOL treatment among survey participants aged 60 years or older in South Korea.

METHODS: This nationwide survey was conducted through in-person interviews using structured questionnaires, from July 24 to August 31, 2023. Eligible participants included individuals aged 60 years or older who had been diagnosed with coronavirus disease 2019 (COVID-19) and received NMVr or MOL. The study outcomes included self-reported demographic, lifestyle, and health characteristics associated with the occurrence of AEs. Multivariate logistic regression analysis was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of each characteristic in participants with and without AEs.

RESULTS: Of the 520 participants, 123 (23.7%) experienced at least one AE with oral COVID-19 treatment: 21.0% (96/458) for NMVr and 43.5% (27/62) for MOL. None of the participants reported any serious AEs. Increased odds of AE occurrence were observed in participants treated with MOL compared to those treated with NMVr (aOR, 3.05; 95% CI, 1.67-5.57), a history of two or more compared to one COVID-19 diagnosis (1.93; 1.03-3.62), and self-reported health status as "Unhealthy" compared to "Healthy" (2.65; 1.31-5.36).

CONCLUSION: No AEs required further evaluation to change treatment strategies in elderly patients on NMVr or MOL. Several factors, including the use of MOL, history of COVID-19, and reported health status, were associated with an increased incidence of AEs. Both treatments may still be useful choices for patients with non-severe COVID-19 aged 60 years or older. However, close monitoring of unidentified potential harm and further investigation of the factors associated with the occurrence of AEs are needed.

PMID:39468947 | DOI:10.3346/jkms.2024.39.e270

BMC Med Res Methodol. 2024 Oct 28;24(1):253. doi: 10.1186/s12874-024-02369-1.

ABSTRACT

BACKGROUND: In randomised controlled trials with efficacy-related primary outcomes, adverse events are collected to monitor potential intervention harms. The analysis of adverse event data is challenging, due to the complex nature of the data and the large number of unprespecified outcomes. This is compounded by a lack of guidance on best analysis approaches, resulting in widespread inadequate practices and the use of overly simplistic methods; leading to sub-optimal exploitation of these rich datasets. To address the complexities of adverse events analysis, statistical methods are proposed that leverage existing structures within the data, for instance by considering groupings of adverse events based on biological or clinical relationships.

METHODS: We conducted a methodological scoping review of the literature to identify all existing methods using structures within the data to detect signals for adverse reactions in a trial. Embase, MEDLINE, Scopus and Web of Science databases were systematically searched. We reviewed the analysis approaches of each method, extracted methodological characteristics and constructed a narrative summary of the findings.

RESULTS: We identified 18 different methods from 14 sources. These were categorised as either Bayesian approaches (n=11), which flagged events based on posterior estimates of treatment effects, or error controlling procedures (n=7), which flagged events based on adjusted p-values while controlling for some type of error rate. We identified 5 defining methodological characteristics: the type of outcomes considered (e.g. binary outcomes), the nature of the data (e.g. summary data), the timing of the analysis (e.g. final analysis), the restrictions on the events considered (e.g. rare events) and the grouping systems used.

CONCLUSIONS: We found a large number of analysis methods that use the group structures of adverse events. Continuous methodological developments in this area highlight the growing awareness that better practices are needed. The use of more adequate analysis methods could help trialists obtain a better picture of the safety-risk profile of an intervention. The results of this review can be used by statisticians to better understand the current methodological landscape and identify suitable methods for data analysis - although further research is needed to determine which methods are best suited and create adequate recommendations.

PMID:39468481 | DOI:10.1186/s12874-024-02369-1

Pharmacol Res Perspect. 2024 Dec;12(6):e70020. doi: 10.1002/prp2.70020.

ABSTRACT

Patients with breast cancer experience various types of adverse events (AEs) during their treatment journey. We aimed to evaluate the incidence, characteristics, and impact of serious AEs in breast cancer patients receiving antineoplastic treatment in the ambulatory setting. A 4-month prospective observational study that included patients with breast cancer treated in the chemotherapy infusion clinics. Patients were assessed for serious AEs, defined as any AE that resulted in a visit to the emergency department (ED) with or without hospital admission, or required any clinical intervention, which were considered as the addition of supportive medications or modifications to the treatment protocol. Characteristics of the patients and antineoplastic regimens as well as the type of AEs were recorded. During the study period, 1168 patients received 2547 cycles. The mean age was 50 ± 11.6 (SD) years and patients had received a median (IQR) of 3 (1-5) treatment cycles prior to enrollment. Among the study cohort, 465 patients(40%) developed at least one serious AE. A total of 660 (26%) cycles were associated with 757 AEs, which required ED visits, addition of supportive medications, and modifications to the treatment protocol in 58%, 29%, and 17% of the cycles, respectively. Most common AEs were musculoskeletal (n = 132, 17%) and gastrointestinal (n = 125, 16.5%). Taxane-based regimens were associated with the most AEs (n = 286, 38%). In a cohort of patients with breast cancer treated in the ambulatory setting, 4 out of 10 patients developed at least one serious AE during the study period. Future research should identify measures to reduce the incidence and severity of such complications.

PMID:39468408 | DOI:10.1002/prp2.70020

Ter Arkh. 2024 Oct 10;96(9):892-900. doi: 10.26442/00403660.2024.09.202984.

ABSTRACT

AIM: To evaluate the long-term safety and efficacy of goflkicept treatment in patients with idiopathic recurrent pericarditis (IRP).

MATERIALS AND METHODS: This report presents the interim analysis of an ongoing open-label extension (OLE) clinical trial of goflkicept in patients with IRP (NCT05673902), as a continuation of the core study (NCT04692766). The study assessed the frequency of pericarditis recurrence, time to recurrence after 12 and 60 weeks of goflkicept therapy, changes in C-reactive protein level, chest pain intensity, pericardial effusion size, and adverse events (AEs).

RESULTS: All patients remained in clinical-laboratory remission during the 60 weeks of goflkicept treatment. The recurrence frequency was 31.3% (5/16) after 60 weeks and 90% (9/10) after 12 weeks of goflkicept treatment (p</i><</i>0.001). A total of 64 AEs were reported in 16 patients (94.1%), mostly of mild to moderate severity. The most common AEs were infections, occurring in 11 patients (64.7%). Nine serious adverse events were reported in 5 patients, none of which were considered drug-related. There were no deaths.

CONCLUSION: Long-term goflkicept therapy resulted in a significant reduction in the risk of recurrence and prolonged remission without an increase in adverse events.

PMID:39467244 | DOI:10.26442/00403660.2024.09.202984

Arthritis Care Res (Hoboken). 2024 Oct 28. doi: 10.1002/acr.25455. Online ahead of print.

ABSTRACT

OBJECTIVE: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission-induction of GPA/MPA. Disease rarity has limited feasibility of similar trials in pediatrics. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for childhood GPA/MPA through registry-based comparative evaluation.

METHODS: From A Registry of Childhood Vasculitis we identified GPA/MPA patients who received induction with RTX or CYC. Pediatric vasculitis activity score (PVAS) and pediatric vasculitis damage index (pVDI) evaluated disease activity and damage. Descriptive statistics summarized patient characteristics. RTX/CYC comparisons used logistic regression for primary outcomes of post-induction remission (PVAS=0) or low disease activity (PVAS<2). Hospital admission for adverse events and pVDI were compared using logistic regression and ordinal regression, respectively.

RESULTS: Among 104 patients, 43% received RTX, 46% CYC, 11% both. Treatment groups did not significantly differ for diagnosis PVAS and onset age. There was no difference in remission between groups (63% overall; OR 1.07, 95% CI: 0.45, 2.52). Hospitalizations occurred in 22% of RTX patients versus 10% on CYC (OR 2.27, 95% CI: 0.73, 7.05). The median 12-month pVDI was one in both groups (OR 0.98, 95% CI 0.43, 2.22).

CONCLUSION: This is the first study comparing CYC and RTX for induction in pediatric GPA/MPA. No significant differences were shown in rates of remission, severe adverse events, or organ damage. Limitations included lack of standardized treatment regimens, retrospectivity, and lack of longitudinal adverse drug-related event data.

PMID:39467015 | DOI:10.1002/acr.25455

J Cosmet Dermatol. 2024 Oct 28. doi: 10.1111/jocd.16652. Online ahead of print.

ABSTRACT

BACKGROUND: Hyaluronic acid (HA) fillers are widely used in aesthetic medicine, but their in vivo behavior and long-term effects are not fully understood.

AIMS: To review the decomposition and changes occurring in the body following HA filler injections, focusing on crosslinking agents, degradation processes, and tissue responses.

METHODS: This review analyzed oxidative and enzymatic degradation processes of HA fillers, evaluated the impact of 1,4-Butanediol Diglycidyl Ether (BDDE) crosslinking, and examined histological changes post-injection.

RESULTS: Uncrosslinked HA degrades rapidly due to endogenous hyaluronidase, while crosslinked HA undergoes slower degradation via free radicals and hyaluronidase. Complete cross-linking (C-MoD) showed better durability compared to partially cross-linked BDDE (P-MoD). The concept of modification efficiency (MoE) was proposed to optimize filler safety and viscoelastic properties. Histological analysis revealed collagen capsule formation and autologous tissue replacement, affecting long-term outcomes. The degree of chemical modification (MoD) influences filler durability and safety, with concerns raised about potential delayed immune reactions from accumulated pendent BDDE.

CONCLUSIONS: Clinicians should consider injection site, tissue conditions, and filler properties for safe and effective HA filler use. Emphasizing thorough BDDE removal and optimal crosslinking can enhance treatment safety and efficacy. The balance between achieving desired viscoelastic properties and minimizing potential risks is crucial. Future studies should include diverse ethnic groups to validate findings and further explore long-term tissue responses to HA fillers.

PMID:39466959 | DOI:10.1111/jocd.16652

Adv Ther. 2024 Oct 28. doi: 10.1007/s12325-024-03023-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis-associated interstitial lung disease (ILD). We present global post-marketing safety data for nintedanib in these fibrosing ILDs.

METHODS: Data on adverse events in patients with fibrosing ILDs who were treated with nintedanib were collected via spontaneous reporting and solicited reporting in various studies (excluding clinical trials). Data were collected from 15 October 2014 (first regulatory approval) to 15 October 2023. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated using sales data.

RESULTS: Cumulative exposure to nintedanib was 380,557 patient-years. Diarrhoea was reported at a rate of 227.5 per 1000 patient-years. Only 2.6% of diarrhoea events were reported as serious. Of 39,788 (33.6%) diarrhoea events with a known time to onset, almost 60% occurred within the first 3 months of treatment. The rate of serious liver enzyme and bilirubin elevations (including drug-induced liver injury) was 4.0 per 1000 patient-years. Bleeding was reported at a rate of 24.2 per 1000 patient-years. Most (81.3%) bleeding events were non-serious. The rates of myocardial infarction, ischaemic stroke, and venous thromboembolism were 3.3, 3.3, and 2.0 per 1000 patient-years, respectively. Gastrointestinal perforation was reported at a rate of 0.9 per 1000 patient-years.

CONCLUSION: Post-marketing safety data on established and potential adverse events associated with nintedanib in patients with fibrosing ILDs, collected over 9 years, demonstrated a safety profile that was similar to that established in clinical trials and provided in the product labels. Education of patients about the adverse events that may be associated with nintedanib, and the effective management of adverse events when they occur, is important to minimise the impact of adverse events and help patients remain on treatment.

PMID:39466587 | DOI:10.1007/s12325-024-03023-4

Hum Vaccin Immunother. 2024 Dec 31;20(1):2387904. doi: 10.1080/21645515.2024.2387904. Epub 2024 Oct 28.

ABSTRACT

The aim of this study was to analyze the incidence and characteristics of adverse events following immunization (AEFI) with post-licensure vaccines used in Hebei province from 2018 to 2020 and to evaluate the safety of vaccines. All information of AEFI was gained from national adverse event following immunization surveillance system (NAEFISS) in Hebei Province from 2018 to 2020. Descriptive epidemiology method was used to analyze the data about AEFI in Hebei province. Reporting rates of AEFI were calculated by sex, age, city, categories of AEFI, severity of AEFI, reaction categories, etc. A total of 35,999 AEFI were reported through NAEFISS, and the average annual rate was 47.64/100,000 doses. The reporting rates of common adverse reactions and rare adverse reactions were 46.37/100,000 doses and 1.05/100,000 doses. The male-to-female ratio was 1.26:1. Most of the AEFI were concentrated in the ≤1 year age group and were reported in the second quarter and third quarter. The majority of AEFI were reported to be recovered or improved, and about 62% of the AEFI occurred within 24 hours after vaccination. Vaccines associated with the highest reporting rate of AEFI were diphtheria, tetanus and acellular pertussis combined vaccine (DTaP, 170.45/100,000 doses). The reporting rate of allergic rash was found to be the highest in the adverse reactions (0.29/100,000 doses). The majority of AEFI cases were common adverse reactions, while serious rare adverse reactions caused by vaccines were extremely uncommon, and all vaccines used in Hebei Province were safe.

PMID:39466071 | DOI:10.1080/21645515.2024.2387904

Neurooncol Adv. 2024 Sep 30;6(1):vdae166. doi: 10.1093/noajnl/vdae166. eCollection 2024 Jan-Dec.

ABSTRACT

BACKGROUND: This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.

METHODS: Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.

RESULTS: Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).

CONCLUSIONS: Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.

PMID:39465217 | PMC:PMC11502913 | DOI:10.1093/noajnl/vdae166

Glob Pediatr Health. 2024 Oct 23;11:2333794X241291398. doi: 10.1177/2333794X241291398. eCollection 2024.

NO ABSTRACT

PMID:39464239 | PMC:PMC11503824 | DOI:10.1177/2333794X241291398

Eur J Hosp Pharm. 2024 Oct 26:ejhpharm-2024-004319. doi: 10.1136/ejhpharm-2024-004319. Online ahead of print.

ABSTRACT

OBJECTIVES: There have been cases of cardiotoxicity induced by osimertinib in patients with non-small-cell lung cancer (NSCLC). However, limited data exist for a comprehensive cardiotoxicity profile analysis for osimertinib use in NSCLC patients. The aim of this study was to report the entire profile of cardiotoxicities after the initiation of osimertinib in consecutive patients with estimated glomerular filtration rate (EGFR) mutation at a single health system.

METHODS: The data were retrospectively collected from electronic medical records for all patients who were started on osimertinib for NSCLC at West Virginia University Health System. Prevalence of heart failure (HF), atrial fibrillation, and prolonged QT before and after starting osimertinib were calculated.

RESULTS: This study had 116 participants and the median age was 72 years. The frequency of each new cardiotoxicity was between 6% and 9%, and the overall percentage of patients who had developed any of the four cardiotoxicities while on osimertinib was 19.9%. The median time of follow-up was 477 days and the median time on osimertinib for all patients was 390 days. The strongest risk factor in predicting a new onset cardiac event was hypertension with a hazard ratio (HR) of 6.35 (confidence interval (CI) 1.48 to 27.23, p=0.013) and HR 5.36 (CI 1.23 to 23.39, p=0.025) in univariate and multivariate analysis respectively.

CONCLUSION: Osimertinib appears to be associated with an increase in cardiac abnormalities. Given the association between this medication exposure and the observed cardiac toxicities, use of osimertinib may entail closer cardiac monitoring of electrocardiogram (ECG) and echocardiogram abnormalities.

PMID:39461730 | DOI:10.1136/ejhpharm-2024-004319