Hum Vaccin Immunother. 2024 Dec 31;20(1):2344970. doi: 10.1080/21645515.2024.2344970. Epub 2024 May 23.

ABSTRACT

This study assessed three Ad26.RSV.preF/RSV preF protein combinations, combining different Ad26.RSV.preF doses and naturally aged preF protein, representing the expected critical vaccine quality attributes close to release, around intermediate shelf-life (ISL) and near-presumed end-of-shelf-life (EoSL), as a way to evaluate the vaccine immunogenicity and safety throughout its shelf-life. A single dose of Ad26.RSV.preF/RSV preF protein vaccine was administered to adults 60-75 years of age. Solicited adverse events (AEs), unsolicited AEs, and serious AEs (SAEs) were assessed for 7-day, 28-day, and 6-month periods after vaccination, respectively. RSV preF-binding antibody concentrations and RSV neutralizing titers were measured 14 days post-vaccination as primary and secondary endpoints, respectively; binding antibodies were also measured 6 months post-vaccination. The RSV preF-binding antibody responses induced by Ad26.RSV.preF/RSV preF protein vaccine lots representing the critical quality attributes around ISL and near presumed EoSL were noninferior to the responses induced by the vaccine lot representing the critical quality attributes near release. The RSV preF-binding and RSV neutralizing antibody levels measured 14 days post-vaccination were similar across the 3 groups. RSV preF-binding antibody concentrations were also similar 6 months post-vaccination. Solicited AEs were mostly mild to moderate in intensity, and a decreased reactogenicity was observed from the Release group to the ISL and EoSL group. None of the reported SAEs were considered related to study vaccination. The study provided evidence of sustained immunogenicity and safety over the intended shelf-life of the Ad26.RSV.pref/RSV preF protein vaccine. The three vaccine lots had acceptable safety profiles.

PMID:38783590 | DOI:10.1080/21645515.2024.2344970

Pharmacoepidemiol Drug Saf. 2024 Jun;33(6):e5819. doi: 10.1002/pds.5819.

ABSTRACT

PURPOSE: This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups.

METHODS: We analyzed medication-related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed.

RESULTS: Among a total of 5071 medication-related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long-term, permanent, and fatal harm. The proportion of medication-related incidents that resulted in harm was the highest among the <1-year-old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication-related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20-64-year age group (256 cases, 11.7%) was 'antibacterials for systemic use', whereas 'contrast media' (236 cases, 11.6%) and 'blood substitutes and perfusion solutions' (98 cases, 19.3%) were the most prevalent drug classes in the ≥65- and <20-year-old age groups, respectively.

CONCLUSIONS: It is necessary to establish guidelines for the prevention of medication-related incidents according to the medication use process and patient age group.

PMID:38783417 | DOI:10.1002/pds.5819

Pharmacoepidemiol Drug Saf. 2024 Jun;33(6):e5820. doi: 10.1002/pds.5820.

ABSTRACT

PURPOSE: Our objective is to describe how the U.S. Food and Drug Administration (FDA)'s Sentinel System implements best practices to ensure trust in drug safety studies using real-world data from disparate sources.

METHODS: We present a stepwise schematic for Sentinel's data harmonization, data quality check, query design and implementation, and reporting practices, and describe approaches to enhancing the transparency, reproducibility, and replicability of studies at each step.

CONCLUSIONS: Each Sentinel data partner converts its source data into the Sentinel Common Data Model. The transformed data undergoes rigorous quality checks before it can be used for Sentinel queries. The Sentinel Common Data Model framework, data transformation codes for several data sources, and data quality assurance packages are publicly available. Designed to run against the Sentinel Common Data Model, Sentinel's querying system comprises a suite of pre-tested, parametrizable computer programs that allow users to perform sophisticated descriptive and inferential analysis without having to exchange individual-level data across sites. Detailed documentation of capabilities of the programs as well as the codes and information required to execute them are publicly available on the Sentinel website. Sentinel also provides public trainings and online resources to facilitate use of its data model and querying system. Its study specifications conform to established reporting frameworks aimed at facilitating reproducibility and replicability of real-world data studies. Reports from Sentinel queries and associated design and analytic specifications are available for download on the Sentinel website. Sentinel is an example of how real-world data can be used to generate regulatory-grade evidence at scale using a transparent, reproducible, and replicable process.

PMID:38783407 | DOI:10.1002/pds.5820

Zhonghua Yi Xue Za Zhi. 2024 May 28;104(20):1790-1803. doi: 10.3760/cma.j.cn112137-20240112-00091.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have emerged as crucial therapeutic agents for various malignancies by activating the host immune system against tumor cells. However, many different types of skin adverse reactions may occur during its use, including eruption, pruritus, blistering, hypopigmentation, alopecia, and even severe cases, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). These cutaneous immune-related adverse events (cirAEs) had a high incidence, which seriously affected patients' quality of life and antitumor treatment decisions. Some severe cutaneous adverse reactions (SCARs) even endanger patients' lives. Therefore, the Chinese Society of Dermatology, the Chinese Dermatologist Association of the Chinese Medical Doctor Association, the Dermatology Division of the Chinese Geriatrics Society, and other relevant experts jointly discussed and formulated the 'Chinese Expert Consensus on the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Related Cutaneous Adverse Reactions'. This consensus covers the name, epidemiology, pathogenesis, clinical features, classification and grading of cirAEs, principles of management and the re-initiation of ICIs. It aims to provide a more scientific and authoritative reference for the diagnosis and treatment of cirAEs in China in the future.

PMID:38782747 | DOI:10.3760/cma.j.cn112137-20240112-00091

J Yeungnam Med Sci. 2024 May 23. doi: 10.12701/jyms.2024.00213. Online ahead of print.

ABSTRACT

This case report is a unique case of solar retinopathy following antidepressant-induced mydriasis and highlights the need for comprehensive ophthalmic evaluation in patients treated with medications having mydriatic effects. A 49-year-old female patient who had received long-term antidepressant therapy presented with bilateral visual impairment after prolonged sun exposure. Fundoscopy confirmed solar retinopathy, which was attributed to drug-induced mydriasis. Medication adjustments and sun protection strategies led to full visual recovery, underscoring the importance of interdisciplinary awareness. This case emphasizes the challenges associated with the simultaneous management of psychiatric and ophthalmic conditions and highlights the need for routine ophthalmic evaluation of patients prescribed antidepressants with reported ocular side effects.

PMID:38778720 | DOI:10.12701/jyms.2024.00213

Reg Anesth Pain Med. 2024 May 20:rapm-2024-105471. doi: 10.1136/rapm-2024-105471. Online ahead of print.

NO ABSTRACT

PMID:38772636 | DOI:10.1136/rapm-2024-105471

Reg Anesth Pain Med. 2024 May 20:rapm-2024-105569. doi: 10.1136/rapm-2024-105569. Online ahead of print.

ABSTRACT

BACKGROUND: Baclofen, a gamma-aminobutyric acid receptor type B agonist in the central nervous system, is the first-line medication among central nervous system modulating agents for the treatment of neurogenic muscle spasticity. While baclofen is most often administered enterally, patients with severe spasticity may be candidates for baclofen delivered by intrathecal pump. Currently, there are only nine studies reporting on the use of intrathecal baclofen (ITB) during pregnancy and childbirth.

CASE PRESENTATION: We described a female patient with a history of childhood idiopathic spasticity of the bilateral lower extremities that was controlled by ITB pump who became pregnant in her late third decade of life and delivered a healthy infant. The patient required multiple increases of her baclofen course over the course of her pregnancy.

DISCUSSION: Our case, alongside the existing literature on ITB during pregnancy, suggests that ITB therapy in pregnancy poses a low risk of teratogenicity and infant withdrawal seizures; however, larger, controlled studies are necessary to make those conclusions with confidence. Healthcare providers caring for pregnant ITB patients should be cognizant of the potential for such patients to require increased doses of ITB during pregnancy to achieve adequate symptom control.

PMID:38772633 | DOI:10.1136/rapm-2024-105569

Int J Biol Macromol. 2024 May 19:132520. doi: 10.1016/j.ijbiomac.2024.132520. Online ahead of print.

ABSTRACT

Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.

PMID:38772463 | DOI:10.1016/j.ijbiomac.2024.132520

Sci Rep. 2024 May 21;14(1):11592. doi: 10.1038/s41598-024-61393-9.

ABSTRACT

A growing body of evidence suggests that adverse drug reactions (ADRs) are a major cause of morbidity and mortality in the healthcare system. Fifteen to twenty-five percent of patients with epilepsy discontinued antiseizure drugs (ASDs) within 6 months of therapy owing to intolerable adverse drug reactions. In Ethiopia, the prevalence of antiseizure adverse drug reactions and associated factors was not extensively conducted in advanced settings like Jimma Medical Centers. Hence, the objective of this study is to assess patterns of adverse drug reactions and associated factors among ambulatory epileptic patients at tertiary hospitals in Ethiopia. A hospital-based prospective observational study was spanned for 1 year. Two hundred ninety patients were consecutively recruited into the study from all epileptic patients attending the ambulatory clinic. Relevant data were collected through patient interviews and medical chart reviews. The causality assessment was done by using the Naranjo Probability Scale. Epi-Data manager version 4.6.0.4 was used for data entry and statistical analysis was performed by Statistical Package for Social Science version 25.0 (SPSS). Stepwise backward logistic regression analysis was done to identify factors that increase the risk of antiseizure adverse drug reactions. The mean (± SD) age of the participants were 29.91(± 11.26) years. The overall prevalence of ADR was 33.8% (95% CI 29.2-39.9%). A total of 110 adverse drug reactions were identified among 98 patients with an average of 1.12 per patient. ADRs were frequently reported with phenobarbital (52.04%) and phenytoin (34.70%). The commonly identified adverse drug reactions were epigastric pain (27.55%) and central nervous system drowsiness (23.46%). Comorbidity (AOR = 5.91, 95% CI (2.14-16.32), seizure-free period of fewer than 2 years (AOR = 1.94, 95% CI (1.18-3.19), and polytherapy (AOR = 1.35, 95% CI (1.80-2.26) were significantly associated with adverse drug reactions. This trial had a comparatively high percentage of adverse medication reactions. Adverse medication reactions were more common in patients with polytherapy, comorbidities, and seizure-free durations less than two years. Therefore, medical practitioners should advise patients who exhibit these traits on how to reduce or avoid bad drug responses or provide comfort in the event of small incidents.

PMID:38773234 | DOI:10.1038/s41598-024-61393-9

Dermatologie (Heidelb). 2024 May 21. doi: 10.1007/s00105-024-05350-7. Online ahead of print.

ABSTRACT

BACKGROUND: Oncological therapies can cause a variety of mucocutaneous adverse events. Exanthematous adverse events can be challenging in the context of the urgent need for cancer treatment due to their spread, sometimes rapid progression, and mucous membrane or organ involvement.

MATERIALS AND METHODS: This article provides an overview of the most important exanthematic dermatoses as side effects of modern drug-based tumor therapies with diagnostic and therapeutic information for clinicians, taking into account the current literature and guidelines.

RESULTS: Exanthematous adverse events of immune checkpoint inhibitors, EGFR antagonists, kinase inhibitors, bispecific T‑cell engagers, and the CCR4 inhibitor mogamulizumab are reviewed in detail.

CONCLUSIONS: Cutaneous side effects are common across all drug classes and cover a broad spectrum. While some adverse events are specific to one drug class, many exanthemas can occur with both oncological immunotherapies and various targeted therapies. A reliable diagnosis, dose adjustment or discontinuation of the offending agent in consultation with the treating oncologists and appropriate symptomatic therapy are important for correct management. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential.

PMID:38772932 | DOI:10.1007/s00105-024-05350-7

Intern Emerg Med. 2024 May 21. doi: 10.1007/s11739-024-03645-0. Online ahead of print.

ABSTRACT

The global increase of aging with the related increase of multiple noncommunicable diseases is inevitably accompanied by the associated issue of multimorbidity and polypharmacy. The latter is not without peculiar consequences on health, because it has been shown to be associated with drug-related adverse events, mainly due to poor prescription appropriateness and drug-drug interactions. To contribute to tackle this gigantic problem, a registry of drug dispensation in hospitalized older patient has been initiated in Italy in 2008. Through the last 15 years, data on nearly 11,000 older people have been accrued during their hospital stay in internal medicine and geriatric wards. This review article summarizes the main findings obtained, and how these data contribute to tackle the issue of appropriateness of drug prescription and the need of deprescribing in hospitalized older people affected by the most common noncommunicable diseases.

PMID:38771425 | DOI:10.1007/s11739-024-03645-0

Clin Case Rep. 2024 May 20;12(5):e8923. doi: 10.1002/ccr3.8923. eCollection 2024 May.

ABSTRACT

Acute neuromuscular paralysis is a relatively common condition in emergency rooms (ERs). They can be caused by several reasons, including adverse drug reactions. Betamethasone is a glucocorticoid commonly used for various conditions, such as allergic conditions. One of the rare but known side effects of glucocorticoids is hypokalemia. Rare cases of hypokalemia following high- and low-dose glucocorticoid injections have been reported. This study presents the history of a young, healthy male without significant past medical history who presented with an inability to stand and walk due to four-limb paralysis (more prominent in the lower limbs) following an intramuscular injection of a 4 mg betamethasone, which was prescribed for the treatment of allergic rhinitis. The patient was stabilized with an intravascular injection of potassium chloride diluted in 1000 mL of normal saline and monitored for 24 h, ruling out any other endocrine condition. Hypokalemia and its severe form are defined as the serum level of lower than 3.5 and 2.5 mEq/Lit, respectively. One of the etiologies of drug-induced hypokalemic paralysis is systemic glucocorticoid administration. In severe cases, it can cause quadriplegia and other neuromuscular, respiratory, and cardiac complications. Therefore, it is an urgent condition that should be managed carefully. Pregnant women who are receiving these medications are a specific group at risk of hypokalemic paralysis. There are several safer treatments for seasonal allergic rhinitis compared to systemic glucocorticoids, which should be considered by physicians. Moreover, paralysis in patients receiving these medications should be approached attentively since it might be caused by hypokalemia, which can be life threatening if not treated. It is advisable that the blood level of electrolytes, especially potassium, be checked for patients who present with paralysis or weakness after glucocorticoid injections.

PMID:38770411 | PMC:PMC11103555 | DOI:10.1002/ccr3.8923

BMC Bioinformatics. 2024 May 20;25(1):196. doi: 10.1186/s12859-024-05806-6.

ABSTRACT

BACKGROUND: The identification of drug side effects plays a critical role in drug repositioning and drug screening. While clinical experiments yield accurate and reliable information about drug-related side effects, they are costly and time-consuming. Computational models have emerged as a promising alternative to predict the frequency of drug-side effects. However, earlier research has primarily centered on extracting and utilizing representations of drugs, like molecular structure or interaction graphs, often neglecting the inherent biomedical semantics of drugs and side effects.

RESULTS: To address the previously mentioned issue, we introduce a hybrid multi-modal fusion framework (HMMF) for predicting drug side effect frequencies. Considering the wealth of biological and chemical semantic information related to drugs and side effects, incorporating multi-modal information offers additional, complementary semantics. HMMF utilizes various encoders to understand molecular structures, biomedical textual representations, and attribute similarities of both drugs and side effects. It then models drug-side effect interactions using both coarse and fine-grained fusion strategies, effectively integrating these multi-modal features.

CONCLUSIONS: HMMF exhibits the ability to successfully detect previously unrecognized potential side effects, demonstrating superior performance over existing state-of-the-art methods across various evaluation metrics, including root mean squared error and area under receiver operating characteristic curve, and shows remarkable performance in cold-start scenarios.

PMID:38769492 | DOI:10.1186/s12859-024-05806-6

Sci Rep. 2024 May 21;14(1):11520. doi: 10.1038/s41598-024-62402-7.

ABSTRACT

Therapeutic drug monitoring (TDM) is a crucial clinical practice that improves pharmacological effectiveness and prevent severe drug-related adverse events. Timely reporting and intervention of critical values during TDM are essential for patient safety. In this study, we retrospectively analyzed the laboratory data to provide an overview of the incidence, distribution pattern and biochemical correlates of critical values during TDM. A total of 19,110 samples were tested for nine drug concentrations between January 1, 2019, and December 31, 2020. Of these, 241 critical values were identified in 165 patients. The most common critical values were vancomycin trough (63.4%), followed by tacrolimus trough (16.9%) and digoxin (15.2%). The primary sources of drug critical values were the department of general intensive care unit (ICU), cardiology, and surgery ICU. At baseline or the time of critical value, significant differences were found between the vancomycin, digoxin, and tacrolimus groups in terms of blood urea nitrogen (BUN), creatinine, N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and lymphocyte percentage, P < 0.05. Therefore, it is important to prioritize and closely monitor drug concentrations to reduce laboratory critical values during TDM.

PMID:38769456 | DOI:10.1038/s41598-024-62402-7

Acta Neurol Belg. 2024 May 20. doi: 10.1007/s13760-024-02572-3. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate postmarketing ocrelizumab safety and effectiveness in a real-world population with multiple sclerosis (MS) and matching these parameters among MS disease types.

METHODS: This was a retrospective, single-center study with MS patients treated with ocrelizumab. Demographic, clinical characteristics and immunological data were analyzed, including annualized relapse rate (ARR), relapse-free rate, Expanded Disability Status Scale (EDSS), complete blood count parameters, immunoglobulin (Ig) levels, liver function tests (LFT), hepatitis markers and adverse events in the 4-year follow-up. A total of 96 patients, 22 with relapsing-remitting MS (RRMS), 54 with secondary progressive MS (SPMS), and 20 with primary progressive MS (PPMS) who were treated with at least two doses of ocrelizumab between January 2018 and September 2023 were included in the study.

RESULTS: Sixty-five (68%) were women and 31 (32%) were men. The mean age was 48.4 ± 11.1 years (20-70 years). Ninety-three patients were evaluated in the first year, 65 in the second year, 39 in the third year and 24 in the fourth year of treatment. 96% of patients were relapse-free rate in the first year, 91% in the second year, 85% in the third year and 75% in the fourth year. Eighty-six percent of patients were progression free in the 1st year of treatment, 71% in the 2nd year, in 64% in the 3rd year, and in 62% in the 4th year. During the follow-up of the cases, EDSS remained stable in 77% of RRMS patients, improved in 14%, and worsened in 9%; while EDSS remained stable in 65% of SPMS patients with attacks, it improved in 9% and worsened in 26%; while EDSS remained stable in 60% of PPMS patients, worsening was observed in 40%. There is a significant decrease in IgM and IgG values during the follow-up of ocrelizumab therapy (p < 0.001, p = 0.014). There is no significant difference in IgA, lymphocyte and neutrophil values (p = 0.713, p = 0.086, p = 0.999). No significant relationship was found between low serum IgM levels and the risk of developing infection (p > 0.05). Liver function tests was found to be within normal limits in 94% of the patients over a 4-year period. No hepatitis B, C or A infection, hepatitis B reactivation, tuberculosis, HIV infection, malignancy or drug related death occurred during 4-years follow-up. The most common side effect during ocrelizumab treatment is urinary tract infection (29%); others were upper respiratory tract infections (13%), numbness/tingling of the face, trunk, or extremities (8%), insomnia (6%), headache (5%), and soft tissue infections (cellulitis and dental abscess, 2%).

CONCLUSIONS: Our results show that ocrelizumab reduces the frequency of attacks and prevent the disease progression in RRMS patients, and reducing the disease progression by primarily stabilizing EDSS scores in SPMS with attacks and PPMS. It is thought that the relatively high rates of urinary tract infection detected in this study may be related with advanced stage of the disease. The absence of hepatitis B reactivation, chronic infection or malignancy in the 4-year follow-up of our cases supports the long-term safety of ocrelizumab treatment. Ocrelizumab may be preferred as an effective and reliable treatment of different types of MS due to non-serious side effects.

PMID:38769274 | DOI:10.1007/s13760-024-02572-3

Qual Life Res. 2024 May 20. doi: 10.1007/s11136-024-03684-2. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to develop and psychometrically evaluate a patient-reported outcome measure (PROM), SAlivary, LAcrimal, NaSal (SALANS), to document patients' symptoms after radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC).

METHODS: We generated and iteratively revised SALANS items based on expert input, focus group discussions and feedback from cognitive testing (n = 17). We administered an initial SALANS measure with 39 items to patients diagnosed with DTC in the past two years (n = 105). Exploratory factor analysis (EFA) examined the factor structure of the SALANS items. We assessed the consistency reliability and related the total and subscale scores of the final SALANS to existing PROMs to assess validity.

RESULTS: The final SALANS consisted of 33 items and six subscales (sialadenitis, taste, xerostomia, dry eyes, epiphora, and nasal) with six factors extracted by EFA. The six subscales demonstrated good internal reliability (α range = 0.87-0.92). The SALANS total score showed good convergent validity with the Xerostomia Inventory (r = 0.86) and good discriminant validity with a measure of spirituality (r = - 0.05). The mean SALANS total score was significantly higher (d = 0.5, p < 0.04) among patients who had RAI compared to those who did not have RAI.

CONCLUSION: Preliminary evidence suggests that SALANS is a novel and reliable PROM to assess the type and frequency all symptoms experienced after RAI treatment for DTC. Future work is needed to further validate and develop the scale.

PMID:38769210 | DOI:10.1007/s11136-024-03684-2

J Cancer Res Clin Oncol. 2024 May 20;150(5):266. doi: 10.1007/s00432-024-05800-8.

ABSTRACT

PURPOSE: Carfilzomib, commonly used for relapsed/refractory multiple myeloma (RRMM), has been associated with various adverse events in randomized controlled trials (RCTs). However, real-world safety data for a more diverse population are needed, as carfilzomib received expedited approval. This study aimed to evaluate carfilzomib's safety in Korea by comparing new users of KRd (carfilzomib, lenalidomide, and dexamethasone) to Rd (lenalidomide and dexamethasone) using a nationwide administrative claims database.

METHODS: The retrospective cohort study utilized target trial emulation, focusing on adverse events in various organ systems similar to the ASPIRE trial.

RESULTS: This study included 4,580 RRMM patients between 2007 and 2020, and the KRd group showed significantly higher risks of hematologic adverse events (anemia, neutropenia, thrombocytopenia) and some non-hematologic adverse events (cough, hypokalemia, constipation, hypertension, heart failure) compared to the Rd group. Among non-hematologic adverse events, cardiovascular events (heart failure [HR 2.04; 95% CI 1.24-3.35], hypertension [HR 1.58; 95% CI 1.15-2.17]) had the highest risk in the KRd group.

CONCLUSION: The safety profile of carfilzomib in Korean patients was similar to previous RCTs. Therefore, caution should be exercised when using carfilzomib in Asian individuals with RRMM due to the increased risk of cardiovascular adverse events.

PMID:38769166 | DOI:10.1007/s00432-024-05800-8

Int J Burns Trauma. 2024 Apr 15;14(2):32-37. doi: 10.62347/GHPO4831. eCollection 2024.

ABSTRACT

This case report describes a unique scenario in which antimycobacterial-induced peripheral neuropathy (PN) culminates in severe bilateral foot frostbite. Drug-induced peripheral neuropathy (DIPN) is explored in the context of TB treatment, highlighting the role of medications such as isoniazid (INH) and their potential to cause PN. The report highlights the importance of identifying PN in patients undergoing antimycobacterial treatment. Early recognition and proper management of PN is crucial to prevent complications. Notably, the report advocates for patient education regarding medication side effects and avoiding harmful practices, such as ice immersion, to alliviate neuropathic pain. Emphasis is directed towards the need for a multidisciplinary approach to patient care and a focus on preventative strategies to improve patient outcomes and avoid severe debilitating complications.

PMID:38764892 | PMC:PMC11101997 | DOI:10.62347/GHPO4831

World J Gastroenterol. 2024 May 14;30(18):2454-2466. doi: 10.3748/wjg.v30.i18.2454.

ABSTRACT

BACKGROUND: Drug-induced liver injury (DILI) is one of the most common adverse events of medication use, and its incidence is increasing. However, early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.

AIM: To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.

METHODS: Saliva samples from 31 DILI patients and 35 healthy controls (HCs) were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry. Subsequent analyses, including partial least squares-discriminant analysis modeling, t tests and weighted metabolite coexpression network analysis (WMCNA), were conducted to identify key differentially expressed metabolites (DEMs) and metabolite sets. Furthermore, we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction. The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.

RESULTS: We found 247 differentially expressed salivary metabolites between the DILI group and the HC group. Using WMCNA, we identified a set of 8 DEMs closely related to liver injury for further prediction testing. Interestingly, the distinct separation of DILI patients and HCs was achieved with five metabolites, namely, 12-hydroxydodecanoic acid, 3-hydroxydecanoic acid, tetradecanedioic acid, hypoxanthine, and inosine (area under the curve: 0.733-1).

CONCLUSION: Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients. Our study may provide a potentially feasible and noninvasive diagnostic method for DILI, but further validation is needed.

PMID:38764769 | PMC:PMC11099387 | DOI:10.3748/wjg.v30.i18.2454

Sci Rep. 2024 May 18;14(1):11367. doi: 10.1038/s41598-024-62238-1.

ABSTRACT

Fulvestrant, as the first selective estrogen receptor degrader, is widely used in the endocrine treatment of breast cancer. However, in the real world, there is a lack of relevant reports on adverse reaction data mining for fulvestrant. To perform data mining on adverse events (AEs) associated with fulvestrant and explore the risk factors contributing to severe AEs, providing a reference for the rational use of fulvestrant in clinical practice. Retrieved adverse event report information associated with fulvestrant from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, covering the period from market introduction to September 30, 2023. Suspicious AEs were screened using the reporting odds ratio (ROR) and proportional reporting ratio methods based on disproportionality analysis. Univariate and multivariate logistic regression analyses were conducted on severe AEs to explore the risk factors associated with fulvestrant-induced severe AEs. A total of 6947 reports related to AEs associated with fulvestrant were obtained, including 5924 reports of severe AEs and 1023 reports of non-severe AEs. Using the disproportionality analysis method, a total of 210 valid AEs were identified for fulvestrant, with 45 AEs (21.43%) not listed in the product labeling, involving 11 systems and organs. The AEs associated with fulvestrant were sorted by frequency of occurrence, with neutropenia (325 cases) having the highest number of reports. By signal strength, injection site pruritus showed the strongest signal (ROR = 658.43). The results of the logistic regression analysis showed that concurrent use of medications with extremely high protein binding (≥ 98%) is an independent risk factor for severe AEs associated with fulvestrant. Age served as a protective factor for fulvestrant-related AEs. The co-administration of fulvestrant with CYP3A4 enzyme inhibitors did not show statistically significant correlation with the occurrence of severe AEs. Co-administration of drugs with extremely high protein binding (≥ 98%) may increase the risk of severe adverse reactions of fulvestrant. Meanwhile, age (60-74 years) may reduce the risk of severe AEs of fulvestrant. However, further clinical research is still needed to explore and verify whether there is interaction between fulvestrant and drugs with high protein binding through more clinical studies.

PMID:38762547 | DOI:10.1038/s41598-024-62238-1