J Clin Pharmacol. 2023 Dec 1. doi: 10.1002/jcph.2389. Online ahead of print.

ABSTRACT

Drug-induced Thrombocytopenia (DIT) deserved both clinical and research attention for the serious clinical consequences and high proportion.The current study aimed to perform a comprehensive pharmacovigilance analysis of DIT reported in the FDA Adverse Event Reporting System (FAERS) database, with a particular focus on drugs associated with Thrombocytopenia events. A disproportionality analysis of DIT was conducted using reports submitted to the FARES from January 2004 to December 2022. The algorithms of Information Component (IC) and Reporting Odds Ratio (ROR) were applied to identify the association between target drugs and DIT events. A total of 15,940,383 cases were gathered in FAERS, 168,657 of which were related to DIT event cases. The top 50 drugs by case number and by signal strength were documented. The top five drugs by case number were lenalidomide (10601 cases), niraparib (3726 cases), ruxolitinib (3624 cases), eltrombopag (3483 cases) and heparin (3478 cases). The top five drugs by signal strength were danaparoid (ROR = 37.61, 95% CI 30.46-46.45), eptifibatide (ROR = 34.75, 95% CI 30.65-39.4), inotersen (ROR = 34.00, 95% CI 29.47-39.23), niraparib (ROR = 30.53, 95% CI 29.42-31.69) and heparin (ROR = 28.84, 95% CI 27.76-29.97). The top 3 involved drug groups were Protein kinase inhibitors, Antimetabolites, and Monoclonal antibodies and antibody-drug conjugates. The current comprehensive pharmacovigilance study identified more drugs associated with thrombocytopenia. While some drugs had been elucidated the mechanisms of DIT, others still required further investigation. This article is protected by copyright. All rights reserved.

PMID:38041205 | DOI:10.1002/jcph.2389

Hepatobiliary Pancreat Dis Int. 2023 Nov 21:S1499-3872(23)00217-5. doi: 10.1016/j.hbpd.2023.11.004. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer-related fatigue (CRF) is a common and debilitating symptom experienced by patients with advanced-stage cancer, especially those undergoing antitumor therapy. This study aimed to evaluate the efficacy and safety of Renshenguben (RSGB) oral solution, a ginseng-based traditional Chinese medicine, in alleviating CRF in patients with advanced hepatocellular carcinoma (HCC) receiving antitumor treatment.

METHODS: In this prospective, open-label, controlled, multicenter study, patients with advanced HCC at BCLC stage C and a brief fatigue inventory (BFI) score of ≥ 4 were enrolled. Participants were assigned to the RSGB group (RSGB, 10 mL twice daily) or the control group (with supportive care). Primary and secondary endpoints were the change in multidimensional fatigue inventory (MFI) score, and BFI and functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores at weeks 4 and 8 after enrollment. Adverse events (AEs) and toxicities were assessed.

RESULTS: A total of 409 participants were enrolled, with 206 assigned to the RSGB group. At week 4, there was a trend towards improvement, but the differences were not statistically significant. At week 8, the RSGB group exhibited a significantly lower MFI score (P < 0.05) compared to the control group, indicating improved fatigue levels. Additionally, the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8 (P < 0.05). Subgroup analyses among patients receiving various antitumor treatments showed similar results. Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI, BFI, and FACT-Hep scores at week 8. No serious drug-related AEs or toxicities were observed.

CONCLUSIONS: RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period, with no discernible toxicities. These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

PMID:38040524 | DOI:10.1016/j.hbpd.2023.11.004

Crit Rev Toxicol. 2023 Dec;53(9):521-571. doi: 10.1080/10408444.2023.2270574. Epub 2023 Dec 5.

ABSTRACT

This scoping review provides an overview of publications reporting adverse effects on the intestines of the food additives carrageenan (CGN) (E 407)/processed Eucheuma seaweed (PES) (E 407a) and carboxymethylcellulose (CMC) (E 466). It includes evidence from human, experimental mammal and in vitro research publications, and other evidence. The databases Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Database of Systematic Reviews and Epistemonikos were searched without time limits, in addition to grey literature. The publications retrieved were screened against predefined criteria. From two literature searches, 2572 records were screened, of which 224 records were included, as well as 38 records from grey literature, making a total of 262 included publications, 196 on CGN and 101 on CMC. These publications were coded and analyzed in Eppi-Reviewer and data gaps presented in interactive maps. For CGN, five, 69 and 33 research publications on humans, experimental mammals and in vitro experiments were found, further separated as degraded or native (non-degraded) CGN. For CMC, three human, 20 animal and 14 in vitro research publications were obtained. The most studied adverse effects on the intestines were for both additives inflammation, the gut microbiome, including fermentation, intestinal permeability, and cancer and metabolic effects, and immune effects for CGN. Further studies should focus on native CGN, in the form and molecular weight used as food additive. For both additives, randomized controlled trials of sufficient power and with realistic dietary exposure levels of single additives, performed in persons of all ages, including potentially vulnerable groups, are needed.

PMID:38032203 | DOI:10.1080/10408444.2023.2270574

Adv Exp Med Biol. 2024;1440:163-191. doi: 10.1007/978-3-031-43883-7_9.

ABSTRACT

Oxysterols or cholesterol oxidation products are a class of molecules with the sterol moiety, derived from oxidative reaction of cholesterol through enzymatic and non-enzymatic processes. They are widely reported in animal-origin foods and prove significant involvement in the regulation of cholesterol homeostasis, lipid transport, cellular signaling, and other physiological processes. Reports of oxysterol-mediated cytotoxicity are in abundance and thus consequently implicated in several age-related and lifestyle disorders such as cardiovascular diseases, bone disorders, pancreatic disorders, age-related macular degeneration, cataract, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, and some types of cancers. In this chapter, we attempt to review a selection of physiologically relevant oxysterols, with a focus on their formation, properties, and roles in health and disease, while also delving into the potential of natural and synthetic molecules along with bacterial enzymes for mitigating oxysterol-mediated cell damage.

PMID:38036880 | DOI:10.1007/978-3-031-43883-7_9

Br J Community Nurs. 2023 Dec 2;28(12):611-614. doi: 10.12968/bjcn.2023.28.12.611.

ABSTRACT

As winter draws on it is timely to look at ways in which nurses in the community may be faced with problems, expected and unexpected, when their patients are particularly affected by cold conditions and at the precautions which need to be taken to avoid or lessen adverse effects on their health. As in the case of heat-related risks to health, examined in an earlier article, so too in the case of cold those most at risk are elderly patients and those who are vulnerable due to a pre-existing condition affecting health even in a more clement climate. Cold weather attracts extra legal responsibilities which are examined in this article.

PMID:38032722 | DOI:10.12968/bjcn.2023.28.12.611

Radiol Case Rep. 2023 Nov 14;19(1):442-444. doi: 10.1016/j.radcr.2023.10.064. eCollection 2024 Jan.

ABSTRACT

This case serves as a reminder of the infrequent, yet consequential occurrence of cerebellar degeneration linked to phenytoin usage. Whilst emphasizes the importance of monitoring patients on long-term phenytoin therapy, and it further suggests considering employing bedside imaging tools such as Ultrasound fusion imaging for follow-up of patients at risk of this type of disorder. We present a case study involving a 23-year-old woman who experienced significant neurological impairment resulting in severe cerebellar atrophy while undergoing phenytoin treatment. On cessation of phenytoin, the patient exhibited improvement with enhanced cerebellar function.

PMID:38033670 | PMC:PMC10684371 | DOI:10.1016/j.radcr.2023.10.064

Postgrad Med. 2023 Nov 21:1-19. doi: 10.1080/00325481.2023.2284650. Online ahead of print.

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality globally. In the major revision of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report, the scientific committee concluded that the use of long-acting β2-agonist/inhaled corticosteroids (LABA/ICS) is not encouraged in patients with COPD. However, current prescribing patterns reveal significant use of LABA/ICS. In this paper, the evidence behind the current practice and the latest treatment recommendations is reviewed. We compare the efficacy and safety of combination therapy with long-acting muscarinic antagonist (LAMA) and LABA vs LABA/ICS and note that LAMA/LABA combinations have reduced the annual rate of moderate/severe exacerbations, delayed the time to first exacerbation, and increased post-dose FEV1 vs ICS-based regimens. The GOLD 2023 report recommends treatment with LABA and LAMA combination (preferably as a single inhaler) in patients with persistent dyspnea, with initiation of ICS in patients based on the symptoms (dyspnea and exercise intolerance as indicated by modified Medical Research Council [mMRC] score ≥ 2 and COPD Assessment Test [CAT™] > 20), blood eosinophil count (≥ 300 cells/µL), and exacerbation history (history of hospitalizations for exacerbations of COPD and ≥ 2 moderate exacerbations per year despite appropriate long-acting bronchodilator maintenance therapy). We describe practical recommendations for primary care physicians to optimize therapy for their patients and prevent overuse of ICS-based regimens. We advocate adherence to current recommendations and a greater focus on effective treatments to successfully control symptoms, minimize exacerbation risk, preserve lung function, maximize patient outcomes, and reduce the burden of drug-related adverse events.

PMID:38032494 | DOI:10.1080/00325481.2023.2284650

Expert Rev Anticancer Ther. 2023 Nov 30. doi: 10.1080/14737140.2023.2290196. Online ahead of print.

ABSTRACT

INTRODUCTION: Ifosfamide is an alkylating chemotherapeutic agent used in the treatment of various neoplasms. Its main adverse effects include renal damage.

AREAS COVERED: A comprehensive review was conducted, including 100 articles from the Scielo, Scopus, and EMBASE databases. Ifosfamide-induced nephrotoxicity is attributed to its toxic metabolites, such as acrolein and chloroacetaldehyde, which cause mitochondrial damage and oxidative stress in renal tubular cells. Literature review found a 29-year average age with no gender predominance and a mortality of 13%. Currently, no fully effective strategy exists for preventing ifosfamide-induced nephrotoxicity; however, hydration, forced diuresis, and other interventions are employed to limit renal damage. Long-term renal function monitoring is essential for patients treated with ifosfamide.

EXPERT OPINION: Ifosfamide remains essential in neoplasm treatment, but nephrotoxicity, often compounded by coadministered drugs, poses diagnostic challenges. Preventive strategies are lacking, necessitating further research. Identifying timely risk factors can mitigate renal damage, and a multidisciplinary approach manages established nephrotoxicity. Emerging therapies may reduce ifosfamide induced nephrotoxicity.

PMID:38031874 | DOI:10.1080/14737140.2023.2290196

J Eur Acad Dermatol Venereol. 2023 Nov 29. doi: 10.1111/jdv.19643. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence on the (long-term) safety of systemic immunomodulating therapies in atopic dermatitis (AD) generated by real-world data is sparse.

OBJECTIVES: To describe real-world reported adverse drug reactions (AEs) related to systemic immunomodulating therapy in patients with AD and to compare the incidence rates of AEs with the Summaries of Product Characteristics (SmPCs).

METHODS: We conducted an observational prospective multi-centre cohort study, using the TREAT NL registry. All severe AEs, AEs of special interest and serious AEs in adult and paediatric patients on systemic immunomodulating treatment (ciclosporin, methotrexate, azathioprine, mycophenolic acid, dupilumab, tralokinumab, baricitinib and upadacitinib) were assessed. Incidences rates of all (potentially) drug-related AEs were standardized in patient years and compared to the cumulative incidences in the associated SmPCs.

RESULTS: We collected 422 patient years of safety data from 266 patients, of whom 129 (48.5%) reported a total of 224 (potentially) drug-related AEs. Compared to dupilumab's SmPC, higher incidence rates were found for four AEs (reported ≥5 times): eosinophilia, blepharitis, dry eyes and head and neck erythema (i.e. dupilumab facial redness). A higher incidence rate of fatigue was found in patients on oral methotrexate in our cohort compared to the SmPC. Two new drug-related AEs (reported ≥5 times) were found in patients on dupilumab, including non-infectious conjunctivitis and meibomian gland dysfunction.

CONCLUSIONS: Real-world reported AEs captured in AD patient registries can add information on the estimated incidence of AEs and benefit clinical decision aids. Future studies using data derived from the TREAT NL registry combined with data from other registries within the TREAT Registry Taskforce will provide more information on (rare) AEs associated with immunomodulating therapy in AD patients.

PMID:38031478 | DOI:10.1111/jdv.19643

Drug Des Devel Ther. 2023 Nov 15;17:3429-3437. doi: 10.2147/DDDT.S426898. eCollection 2023.

ABSTRACT

Anti-angiogenesis therapy plays a vital role in the treatment of tumors, with anlotinib as its representative targeted drug. Anlotinib is a novel oral tyrosine kinase inhibitor (TKI) with inhibitory effects on tumor growth tumor angiogenesis. In Phase III clinical trials, anlotinib demonstrated better overall survival and progression-free survival than placebo in patients with advanced non-small cell lung cancer (NSCLC), and was approved for the first time as a third-line treatment for refractory advanced NSCLC. Going far beyond that, anlotinib has shown encouraging results in a variety of malignancies, including medullary thyroid carcinoma, renal cell carcinoma, gastric cancer and esophageal squamous cell carcinoma. Nevertheless, anlotinib has been subject to some controversy in terms of adverse events due to its widespread use. In this review, the mechanism of action, pharmacokinetic characteristics, adverse reactions in clinical use and management of anlotinib were summarized.

PMID:38024530 | PMC:PMC10657757 | DOI:10.2147/DDDT.S426898

Asian Pac J Cancer Prev. 2023 Nov 1;24(11):3795-3804. doi: 10.31557/APJCP.2023.24.11.3795.

ABSTRACT

BACKGROUND: Oxidative stress combined with nullity of xenobiotic metabolizing GSTT1/GSTM1/CYP2E1 genes may increase the susceptibility of agricultural workers to adverse health effects including cancer. The present study was conducted to determine; the prevalence of polymorphisms in GSTM1, GSTT1 and CYP2E1 genes, serum 8-hydroxy-2'-deoxygunosine levels, and the role of these markers in risk of cancer among agricultural workers occupationally exposed to pesticides.

METHODS: A total of 360 participants, of which 180 belonging to farming group diagnosed with leukemia (n=60), lymphoma (n=60) and breast cancers (n=60), 90 in non-farming group diagnosed with similar cancers and the other 90 as healthy controls with neither history of occupational exposure nor diagnosed with any type of cancers were recruited. Following the questionnaire survey, serum 8-OHdG and genetic polymorphisms in the three genes were determined using ELISA and PCR methods respectively.

RESULTS: The results of the study revealed that farm workers carrying GSTT1 null genotype had increased risk for lymphoma (OR = 5.34; 95% CI = 1.80-15.82) and breast cancer (OR=4.04; 95% CI = 1.24-13.07). For farm workers carrying GSTM1 null genotype, the risk was six-fold for breast cancer (OR = 6.88; 95% CI =1.88-25.99). Further, there found a significant difference between 8-OHdG and nullity of CYP2E1 among the farm workers diagnosed with leukemia.

CONCLUSION: The findings of the present study suggest that the polymorphisms in detoxifying genes among farm workers occupationally exposed to pesticides and the oxidative stress may likely be responsible for triggering the mechanism of malignancy.

PMID:38019237 | DOI:10.31557/APJCP.2023.24.11.3795

J Int Med Res. 2023 Nov;51(11):3000605231214065. doi: 10.1177/03000605231214065.

ABSTRACT

Adverse drug reactions represent a major health burden because they cause notable patient morbidity and mortality. From this viewpoint, several strategies have been developed to prevent or reduce adverse drug reactions. One such strategy is the use of pharmacogenomics. Interindividual variability in drug response and adverse effects is mainly attributable to genetic variation in enzymes such as sulfotransferases and cytochrome P450s. The current narrative review discusses the relationship between the structure and activity of drugs. Specifically, the activity of drugs can be increased and/or their adverse effects can be reduced by altering specific positions in their structures.

PMID:38019107 | DOI:10.1177/03000605231214065

Int J Oral Maxillofac Surg. 2023 Nov 28:S0901-5027(23)00875-5. doi: 10.1016/j.ijom.2023.11.001. Online ahead of print.

ABSTRACT

The objective of this study was to identify the prevalence of osteonecrosis of the jaw in a pediatric population with systemic therapeutic exposure to an antiresorptive, anti-angiogenic, and/or immunomodulating drug (ARAID), and in particular in the subgroup of patients who had undergone invasive dental treatment. This was a retrospective cohort study performed at a single center. The investigation included pediatric patients who had undergone systemic therapy with ARAIDs and who began receiving ARAID therapy at ≤16 years of age. The study included 482 patients who received ARAIDs between January 2011 and January 2021. The most common medication class was bisphosphonates (45.0%), followed by mTOR inhibitors (30.1%) and anti-angiogenics (17.8%). No diagnosis of osteonecrosis of the jaw was observed. From this population, 26 patients were noted to have undergone invasive dental treatment. The duration from treatment to the invasive procedure ranged from 0 to 5.9 years. Medication-related osteonecrosis of the jaw is extremely rare among the pediatric population - much less common when compared to the adult population. Prospective cohort studies and continued evaluation will help determine the incidence and prevalence of medication-related osteonecrosis of the jaw in pediatric patients.

PMID:38030483 | DOI:10.1016/j.ijom.2023.11.001

Seizure. 2023 Nov 22;114:9-17. doi: 10.1016/j.seizure.2023.11.010. Online ahead of print.

ABSTRACT

PURPOSE: The Liverpool Adverse Event Profile (L AEP) is commonly applied in clinical practice and pharmacological trials for the monitoring of side effects of anti-seizure medication (ASM). However, additional symptoms need to be assessed and normative data would be appreciated to put patients´ complaints into perspective.

METHODS: An extended 32-item AEP (E AEP) was given to 537 healthy subjects and 1,605 patients with epilepsy as part of the Bonn ASM side effect registry. The tool was factor-analyzed, normed with regard to age, gender, and repeated application, and related to drug load and individual substances (with N> 100) on item and scale level (total E AEP and its subscales cognition, dizziness, energy, mood, bodily symptoms, aggression, and sexuality).

RESULTS: Compared to non-normalized results, on item level, between one and two-thirds less problematic responses were noted after normalization. Binary regression analyses revealed differential effects of antiseizure-drug treatment, but also of antidepressants and neuroleptics on complaint domains. The explained variance was better for bodily than psychic domains. The results reflect both known drug side effects and indications. Patients´ explicit attribution of problems to their drugs barely improved the correlation of the E AEP and treatment parameters.

CONCLUSION: Application of a normed AEP is highly recommended to avoid an overestimation of treatment related problems in patients with epilepsy. It allows evaluation on item and scale level for individuals as well as groups in drug trials. Plausible relations to individual drugs and to drug load can be demonstrated. The explanatory power was better for physical than psychic domains. Drug-related complaint patterns reflect known drug side effects (e.g. perampanel and brivaracetam with aggression) as well as drug indications (e.g. lamotrigine for depression), the latter particularly when considerations of side effects found their way into treatment decisions. Longitudinal evaluation with repeated application of the E AEP along with changes of drug treatment is in progress.

PMID:38029647 | DOI:10.1016/j.seizure.2023.11.010

Front Genet. 2023 Nov 7;14:1238140. doi: 10.3389/fgene.2023.1238140. eCollection 2023.

ABSTRACT

Introduction: Scientific articles serve as vital sources of biomedical information, but with the yearly growth in publication volume, processing such vast amounts of information has become increasingly challenging. This difficulty is particularly pronounced when it requires the expertise of highly qualified professionals. Our research focused on the domain-specific articles classification to determine whether they contain information about drug-induced liver injury (DILI). DILI is a clinically significant condition and one of the reasons for drug registration failures. The rapid and accurate identification of drugs that may cause such conditions can prevent side effects in millions of patients. Methods: Developing a text classification method can help regulators, such as the FDA, much faster at a massive scale identify facts of potential DILI of concrete drugs. In our study, we compared several text classification methodologies, including transformers, LSTMs, information theory, and statistics-based methods. We devised a simple and interpretable text classification method that is as fast as Naïve Bayes while delivering superior performance for topic-oriented text categorisation. Moreover, we revisited techniques and methodologies to handle the imbalance of the data. Results: Transformers achieve the best results in cases if the distribution of classes and semantics of test data matches the training set. But in cases of imbalanced data, simple statistical-information theory-based models can surpass complex transformers, bringing more interpretable results that are so important for the biomedical domain. As our results show, neural networks can achieve better results if they are pre-trained on domain-specific data, and the loss function was designed to reflect the class distribution. Discussion: Overall, transformers are powerful architecture, however, in certain cases, such as topic classification, its usage can be redundant and simple statistical approaches can achieve compatible results while being much faster and explainable. However, we see potential in combining results from both worlds. Development of new neural network architectures, loss functions and training procedures that bring stability to unbalanced data is a promising topic of development.

PMID:38028616 | PMC:PMC10668010 | DOI:10.3389/fgene.2023.1238140

Clin Case Rep. 2023 Nov 20;11(11):e8247. doi: 10.1002/ccr3.8247. eCollection 2023 Nov.

ABSTRACT

KEY CLINICAL MESSAGE: Drug-induced pleural effusion is extremely rare. It is the diagnosis of exclusion. This condition can be suspected if the patient has been exposed to a likely causative drug, develops new signs and symptoms, and has a remittance of these symptoms once the drug is withheld.

ABSTRACT: Etoricoxib has been a very popular nonsteroidal anti-inflammatory drug and is prescribed widely due to its fewer gastrointestinal side effects. Pleural effusion caused by etoricoxib is rarest among the side effects. Here, we report a case of a 45-year-old female with pleural effusion induced by etoricoxib.

PMID:38028070 | PMC:PMC10661311 | DOI:10.1002/ccr3.8247

Open Med (Wars). 2023 Oct 30;18(1):20230823. doi: 10.1515/med-2023-0823. eCollection 2023.

ABSTRACT

Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease with various immune system manifestations, showing a global trend of increased prevalence. AIH is diagnosed through histological abnormalities, clinical manifestations, and biochemical indicators. The biochemical markers involve interfacial hepatitis, transaminase abnormalities, positive autoantibodies, etc. Although AIH pathogenesis is unclear, gene mutations and immunological factors could be the leading factors. AIH usually presents as a chronic liver disease and sometimes as acute hepatitis, making it challenging to distinguish it from drug-related hepatitis due to similar clinical symptoms. Normalizing transaminases and serum IgG levels is essential in assessing the remission status of AIH treatment. Glucocorticoids and azathioprine are the first-line AIH treatment, with lifelong maintenance therapy in some patients. The quality of life and survival can be improved after appropriate treatment. However, certain limitations jeopardize the quality of treatment, including long treatment cycles, side effects, poor patient compliance, and inability to inhibit liver fibrosis and cirrhosis. Accurate AIH animal models will help us understand the pathophysiology of the disease while providing fresh perspectives for avoiding and treating AIH. This review will help us understand AIH better, from the cellular and molecular causes to the clinical features, and will provide insight into new therapy techniques with fewer side effects.

PMID:38025543 | PMC:PMC10655690 | DOI:10.1515/med-2023-0823

J Pediatr Pharmacol Ther. 2023;28(7):643-648. doi: 10.5863/1551-6776-28.7.643. Epub 2023 Nov 23.

ABSTRACT

PURPOSE: Etoposide, a topoisomerase II inhibitor used clinically to treat cancer, has been associated with severe anaphylactic infusion related adverse drug reactions (ADRs). In a previous study we identified a hydrophilic polyethersulfone filter as a possible cause of increased rates of pediatric etoposide infusion reactions. In this multidisciplinary follow-up analytical study, we aimed to assess the chemical structure of etoposide after passing through the same hydrophilic polyethersulfone filter.

METHODS: An etoposide 0.4 mg/mL infusion was prepared under aseptic conditions and then passed through a standard IV infusion set with an in-line filter in place. Samples were taken in triplicate using a needle-less access system to include sampling sites directly from the IV bag port and from the IV tubing both before and after the in-line filter. Samples were diluted into mobile phase, then an aliquot was injected into a high-performance liquid chromatography mass spectrometry HPLC-MS (Thermo TSQ Quantum Ultra) system coupled to a Diode Array Detector (DAD) (Thermo Dionex Ultimate 3000). Etoposide was monitored using a selected reaction monitoring scan (SRM) of 606.2/228.8 and wavelengths of 210, 220, 254, and 280 nm for 30 minutes.

RESULTS: No detectable differences were observed upon comparing the three samples. Based on these results, a chemical change in etoposide resulting from an in-line filter is unlikely to be the primary cause of increased rates of infusion reactions.

CONCLUSION: Pharmacists working in healthcare systems, observe many ADRs, but rarely have the resources necessary to investigate the potential etiology or causality. This report highlights importance of multi-disciplinary collaboration to investigate serious ADRs.

PMID:38025152 | PMC:PMC10681083 | DOI:10.5863/1551-6776-28.7.643

EJHaem. 2023 Oct 3;4(4):1110-1116. doi: 10.1002/jha2.801. eCollection 2023 Nov.

ABSTRACT

Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug-induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin-related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose-response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.

PMID:38024642 | PMC:PMC10660614 | DOI:10.1002/jha2.801

Front Oncol. 2023 Nov 13;13:1227461. doi: 10.3389/fonc.2023.1227461. eCollection 2023.

ABSTRACT

BACKGROUND: Effective adjuvant therapy for osteosarcoma is necessary for improved outcomes. Previous studies demonstrated that apatinib plus doxorubicin-based chemotherapy may improve the efficacy of neoadjuvant therapy. This study aimed to clarify the effectiveness and safety of apatinib plus doxorubicin and cisplatin (AP) as neoadjuvant therapy for osteosarcoma.

METHODS: The clinical data of osteosarcoma patients who underwent neoadjuvant therapy and surgery between August 2016 and April 2022 were retrospectively collected and analyzed. Patients were divided into two groups: the apatinib plus AP (apatinib + AP) group and the methotrexate, doxorubicin, and cisplatin (MAP) group.

RESULTS: This study included 42 patients with nonmetastatic osteosarcoma (19 and 23 patients in the apatinib + AP and MAP groups, respectively). The 1- and 2-year disease-free survival rates in the apatinib + AP group were higher than those in the MAP group, but the difference was not significant (P=0.165 and 0.283, respectively). Some adverse events were significantly more common in the apatinib + AP group than in the MAP group, including oral mucositis (grades 3 and 4) (52.6% vs. 17.4%, respectively, P=0.023), limb edema (47.4% vs. 17.4%, respectively, P=0.049), hand-foot syndrome (31.6% vs. 0%, respectively, P=0.005), proteinuria (26.3% vs. 0%, respectively, P=0.014), hypertension (21.1% vs. 0%, respectively, P=0.035), and hypothyroidism (21.1% vs. 0%, respectively, P=0.035). No drug-related deaths occurred. There was no statistically significant difference in the incidence of postoperative complications between the groups (P>0.05).

CONCLUSION: The present study suggests that apatinib + AP may be a promising candidate for neoadjuvant therapy for osteosarcoma, warranting further validation in prospective randomized controlled clinical trials with long-term follow-up.

PMID:38023239 | PMC:PMC10679406 | DOI:10.3389/fonc.2023.1227461