J Med Virol. 2024 Jul;96(7):e29792. doi: 10.1002/jmv.29792.

ABSTRACT

Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.

PMID:38993028 | DOI:10.1002/jmv.29792

Pharmacol Res Perspect. 2024 Aug;12(4):e1245. doi: 10.1002/prp2.1245.

NO ABSTRACT

PMID:38992909 | DOI:10.1002/prp2.1245

Mol Imaging Biol. 2024 Jul 11. doi: 10.1007/s11307-024-01933-x. Online ahead of print.

ABSTRACT

PURPOSE: Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer. Recently, a probe has been developed that only fluoresces when activated in an acidic pH, which is common to many malignancies. We report the first multicenter Phase 2 trial of a pH-activatable nanoprobe (pegsitacianine, ONM-100) for IMI of lung cancer.

METHODS: Patients with suspected or biopsy-confirmed lung cancer scheduled for sublobar resection were administered a single intravenous infusion of pegsitacianine (1 mg/kg) one to three days prior to surgery. Intraoperatively, the patients underwent a white light thoracoscopic evaluation, and then were imaged with an NIR thoracoscope to detect tumor fluorescence. The primary study endpoint was the proportion of patients with a clinically significant event (CSE) which was defined as an intraoperative discovery during IMI that led to a change in the surgical procedure. Possible CSEs included (i) localizing the index lung nodule that could not be located by white light, (ii) identifying a synchronous malignant lesion, or (iii) recognizing a close surgical margin (< = 10 mm). Secondary endpoints were sensitivity, specificity, NPV, and PPV of pegsitacianine in detecting tumor-containing tissue. The safety evaluation was based on adverse event reporting, clinical laboratory parameters, and physical examinations.

RESULTS: Twenty patients were confirmed as eligible and administered pegsitacianine. Most of the patients were female (n = 12 [60%]), middle-aged (mean age 63.4 years), and former smokers (n = 13 [65%], 28.6 mean pack years). Mean lesion size was 1.9 cm, and most lesions (n = 17 [85%]) were malignant. The most common histologic subtype was adenocarcinoma (n = 9). By utilizing IMI with pegsitacianine, one patient had a CSE in the detection of a close margin and another had localization of a tumor not detectable by traditional surgical means. Six of 19 (31.6%) malignant lesions fluoresced with mean tumor-to-background ratio (TBR) of 3.00, as compared to TBR of 1.20 for benign lesions (n = 3). Sensitivity and specificity of pegsitacianine-based IMI for detecting malignant tissue was 31.6% and 33.3%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of pegsitacianine-based IMI was 75% and 7.1%, respectively. Pegsitacianine-based imaging was not effective in differentiating benign and malignant lymph nodes. From a safety perspective, no drug-related serious adverse events occurred. Four patients experienced mild pegsitacianine-related infusion reactions which required discontinuing the study drug with complete resolution of symptoms.

CONCLUSIONS: Pegsitacianine-based IMI, though well tolerated from a safety perspective, does not consistently label lung tumors during resection and does not provide significant clinical benefit over existing standards of surgical care. The biology of lung tumors may not be as acidic as other solid tumors in the body thereby not activating the probe as predicted.

PMID:38992245 | DOI:10.1007/s11307-024-01933-x

Hepatol Res. 2024 Jul 11. doi: 10.1111/hepr.14092. Online ahead of print.

ABSTRACT

AIM: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population.

METHODS: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders.

RESULTS: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis.

CONCLUSIONS: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome.

CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry with the number UMIN000043798.

PMID:38990762 | DOI:10.1111/hepr.14092

Curr Drug Saf. 2024;19(3):317-331. doi: 10.2174/0115748863276456231016062628.

ABSTRACT

BACKGROUND: Healthcare professionals play an essential role in reporting adverse drug reactions as part of pharmacovigilance activities. However, adverse drug reactions reported by healthcare professionals remain low.

OBJECTIVE: The aim of this systematic review was to investigate healthcare professionals' knowledge, awareness, attitude, and practice on pharmacovigilance and adverse drug reaction reporting, explore the causes of the underreporting issue, and provide improvement strategies.

METHODS: This systematic review was conducted using four electronic databases for original papers, including PubMed, Scopus, Google Scholar, and Scholar ID. Recent publications from 1st January 2012 to 31st December 2022 were selected. The following terms were used in the search: "awareness", "knowledge", "adverse drug reaction", "pharmacovigilance", "healthcare professional", and "underreporting factor". Articles were chosen, extracted, and reviewed by the two authors.

RESULTS: Twenty-five studies were selected for systematic review. This review found that 24.8%-73.33% of healthcare professionals were unaware of the National Pharmacovigilance Center. Around 20%-95.7% of healthcare professionals have a positive attitude toward pharmacovigilance and adverse drug reaction reporting, while 12%-60.8% of healthcare professionals have experience reporting any adverse drug reaction in their practice. The most frequently highlighted barriers to pharmacovigilance were a lack of awareness and knowledge regarding what, when, and to whom to report.

CONCLUSION: Underreporting issues require immediate attention among healthcare professionals due to a lack of awareness and knowledge of pharmacovigilance and adverse drug reaction reporting. Educational and training program interventions have been suggested by most studies to address these issues.

PMID:38989832 | DOI:10.2174/0115748863276456231016062628

Iran J Child Neurol. 2024 Summer;18(3):151-157. doi: 10.22037/ijcn.v18i3.18054. Epub 2024 Jun 22.

ABSTRACT

Extrapyramidal symptoms (EPS) that include akathisia, dystonia, pseudoparkinsonism, and dyskinesia are abnormal movements commonly induced by antipsychotic medications. These symptoms are also associated with specific non-antipsychotic agents. This case report describes a case of a 9-year-old boy on antibiotics treatment that developed EPS. A 9-year-old boy presented to the emergency department of Imam Hossein Children›s Hospital with chief complaints of trismus, difficulty speaking, and tongue protrusion. One week before these presentations, he had been prescribed Tavanex® (levofloxacin) and clindamycin. His symptoms improved after the withdrawal of antibiotics and administering Biperiden, and he was discharged in good condition. On a follow-up visit one week after discharge, no remaining symptoms were present, and he was in good condition. Based on the questions in the Naranjo criteria, levofloxacin receives a score of 7 and is a probable cause of adverse drug reaction (ADR). Clindamycin, with a score of 6, is also a probable cause for this adverse drug reaction, but clinical judgment was in favor of levofloxacin as the culprit. Clinicians should be aware of the potential EPS of levofloxacin at standard doses. Effective management of adverse events is necessary to ensure patient safety and optimal outcomes.

PMID:38988842 | PMC:PMC11231684 | DOI:10.22037/ijcn.v18i3.18054

Schizophr Res. 2024 Jul 9;270:383-391. doi: 10.1016/j.schres.2024.06.033. Online ahead of print.

ABSTRACT

BACKGROUND: Extensive research has been undertaken to predict treatment response (TR) to antipsychotics. Most studies address TR to antipsychotics in general and as monotherapy, however, it is unknown whether patients might respond favourably to a combination of antipsychotics.

AIMS: This study aimed to identify differential predictors for TR to monotherapy with amisulpride or olanzapine compared to a combination of antipsychotics.

METHODS: Post-hoc analysis was conducted of data collected from the COMBINE-study, a double-blind, randomized, controlled trial. Demographic and disease-related measures were gathered at baseline to predict TR after eight weeks defined by the Positive and Negative Syndrome Scale. Missing values were accounted for by a random replacement procedure. Attrition effects and multicollinearity were analysed and sets of logistic regression models were calculated for different treatment groups.

RESULTS: Of the 321 randomized patients, 201 completed procedures until week eight and 197 were included in the analyses. For all treatment groups, early TR after two weeks and high subjective well-being under antipsychotics at baseline were robust predictors for TR. The propensity for early side effects also indicated a higher risk of later non-response. Specific parameter estimates were rather similar between treatment groups.

CONCLUSION: Early TR, drug-related subjective well-being, and early side effect propensity evolved as predictors for later TR whether to monotherapy or combination strategy. Accordingly, due to a lack of differential predictors, early and close monitoring of targeted and unwanted effects is indicated to guide respective treatment decisions.

PMID:38986385 | DOI:10.1016/j.schres.2024.06.033

Front Oncol. 2024 Jun 24;14:1426796. doi: 10.3389/fonc.2024.1426796. eCollection 2024.

ABSTRACT

The advent of targeted drug therapy has greatly changed the treatment landscape of advanced non-small cell lung cancer(NSCLC), but the cardioxic side effects of targeted drug anti-cancer therapy seriously affect the prognosis of NSCLC, and it has become the second leading cause of death in cancer patients. Therefore, early identification of the cardiotoxic side effects of targeted drugs is crucial for the prevention and treatment of cardiovascular diseases. The cardiotoxic side effects that may be caused by novel targeted drugs epidermal growth factor receptor inhibitors, including thromboembolic events, heart failure, cardiomyopathy, arrhythmia and hypertension, are discussed, and the mechanisms of their respective adverse cardiovascular reactions are summarized, to provide useful recommendations for cardiac management of patients with advanced lung cancer to maximize treatment outcomes for lung cancer survivors. Clinicians need to balance the risk-benefit ratio between targeted therapy for malignant tumors and drug-induced cardiotoxicity, and evaluate and monitor TKIs-induced cardiotoxicity through electrocardiogram, cardiac imaging, biomarkers, etc., so as to remove the susceptibility risk factors as soon as possible and provide a reference for the clinical use of such drugs in the treatment of malignant tumors.

PMID:38983928 | PMC:PMC11232364 | DOI:10.3389/fonc.2024.1426796

Cancer Sci. 2024 Jul 9. doi: 10.1111/cas.16234. Online ahead of print.

ABSTRACT

The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.

PMID:38979893 | DOI:10.1111/cas.16234

Am J Ther. 2024 Jul-Aug 01;31(4):e356-e361. doi: 10.1097/MJT.0000000000001686.

ABSTRACT

BACKGROUND: Flumazenil is a competitive benzodiazepine (BZD) antagonist most used for treating delirium in BZD overdoses. Since its introduction, many have expressed concerns about its safety secondary to the risk of inducing BZD withdrawal and refractory seizures.

STUDY QUESTION: What is the incidence of adverse drug events after the administration of flumazenil in patients with suspected iatrogenic BZD delirium?

STUDY DESIGN: This is a retrospective cross-sectional study of patients from a single center from 2010 to 2013. Patients experiencing delirium after receiving BZDs in the hospital were included if they had a bedside toxicology consult and were administered flumazenil. Patients were excluded if they were given BZDs for ethanol withdrawal or if they did not have mental status documentation before and after flumazenil administration. Descriptive statistics were calculated.

MEASURES AND OUTCOMES: The primary outcome was the incidence of adverse drug events after flumazenil administration. The secondary outcome was the efficacy of flumazenil determined by the patient's mental status.

RESULTS: A total of 501 patient records were reviewed, and 206 patients were included in the final analysis. Of those patients, 172 (83.5%) experienced an objective improvement in their mental status within 1 hour after flumazenil administration. A total of 5 patients experienced adverse events (2.4%), 95% confidence interval (0.78, 5.54). Of these, 3 patients experienced minor agitation or restlessness without pharmacologic intervention. Two patients experienced moderate agitation or restlessness that resolved with haloperidol or physostigmine administration. No patients had a reported seizure, 95% confidence interval (0.0, 1.77).

CONCLUSIONS: Flumazenil seems to be a safe and effective intervention for the reversal of delirium secondary to iatrogenic BZD administration.

PMID:38976524 | DOI:10.1097/MJT.0000000000001686

BMC Psychiatry. 2024 Jul 8;24(1):491. doi: 10.1186/s12888-024-05668-5.

ABSTRACT

BACKGROUND: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone.

CASE PRESENTATION: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic.

CONCLUSIONS: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

PMID:38977949 | DOI:10.1186/s12888-024-05668-5

Clin Transl Gastroenterol. 2024 Jul 1. doi: 10.14309/ctg.0000000000000744. Online ahead of print.

ABSTRACT

OBJECTIVES: This proof-of-concept, open-label phase 1b study evaluated the safety and efficacy of cilofexor, a potent selective farnesoid X receptor agonist, in patients with compensated cirrhosis due to primary sclerosing cholangitis (PSC).

METHODS: Escalating doses of cilofexor (30 mg [weeks 1-4], 60 mg [weeks 5-8], 100 mg [weeks 9-12]) were administered orally once daily over 12 weeks. The primary endpoint was safety. Exploratory measures included cholestasis and fibrosis markers, and pharmacodynamic biomarkers of bile acid homeostasis.

RESULTS: Eleven patients were enrolled (median age: 48 years; 55% men). The most common treatment-emergent adverse events (TEAEs) were pruritus (8/11 [72.7%]), fatigue, headache, nausea, and upper respiratory tract infection (2/11 [18.2%] each). Seven patients experienced a pruritus TEAE (one grade 3) considered drug related. One patient temporarily discontinued cilofexor owing to peripheral edema. There were no deaths, serious TEAEs, or TEAEs leading to permanent discontinuation. Median changes (interquartile ranges) from baseline to week 12 (predose, fasting) were -24.8% (-35.7, -7.4) for alanine transaminase, -13.0% (-21.9, -8.6) for alkaline phosphatase, -43.5% (-52.1, -30.8) for gamma-glutamyl transferase, -12.7% (-25.0, 0.0) for total bilirubin, and -21.2% (-40.0, 0.0) for direct bilirubin. Least-squares mean percentage change (95% confidence interval) from baseline to week 12 at trough was -55.3% (-70.8, -31.6) for C4 and -60.5% (-81.8, -14.2) for cholic acid. Fasting fibroblast growth factor 19 levels transiently increased after cilofexor administration.

CONCLUSIONS: Escalating doses of cilofexor over 12 weeks were well tolerated and improved cholestasis markers in patients with compensated cirrhosis due to PSC (NCT04060147).

PMID:38976363 | DOI:10.14309/ctg.0000000000000744

Transl Clin Pharmacol. 2024 Jun;32(2):83-97. doi: 10.12793/tcp.2024.32.e7. Epub 2024 May 29.

ABSTRACT

Safety pharmacology examines the potential for new drugs to have unusual, rare side effects such as torsade de pointes (TdP). Recently, as a part of the Comprehensive in vitro Proarrhythmia Assay (CiPA) project, techniques for predicting the development of drug-induced TdP through computer simulations have been proposed and verified. However, CiPA assessment generally does not consider the effect of cardiac cell inter-individual variability, especially related to metabolic status. The study aimed to explore whether rare proarrhythmic effects may be linked to the inter-individual variability of cardiac cells and whether incorporating this variability into computational models could alter the prediction of drugs' TdP risks. This study evaluated the contribution of two biological characteristics to the proarrhythmic effects. The first was spermine concentration, which varies with metabolic status; the second was L-type calcium permeability that could occur due to mutations. Twenty-eight drugs were examined throughout this study, and qNet was analyzed as an essential feature. Even though there were some discrepancies of TdP risk predictions from the baseline model, we found that considering the inter-individual variability might change the TdP risk of drugs. Several drugs in the high-risk drugs group were predicted to affect as intermediate and low-risk drugs in some individuals and vice versa. Also, most intermediate-risk drugs were expected to act as low-risk drugs. When compared, the effects of inter-individual variability of L-type calcium were more significant than spermine in altering the TdP risk of compounds. These results emphasize the importance of considering inter-individual variability to assess drugs.

PMID:38974343 | PMC:PMC11224897 | DOI:10.12793/tcp.2024.32.e7

Pharmacoepidemiol Drug Saf. 2024 Jul;33(7):e5853. doi: 10.1002/pds.5853.

ABSTRACT

BACKGROUND: Adverse drug events (ADEs) are a frequent cause of injury in patients. Our aim was to assess whether pharmacist interventions compared with no pharmacist intervention results in reduced ADEs and potential adverse drug events (PADEs).

METHODS: We searched MEDLINE, Embase, and two other databases through September 19, 2022 for any RCT assessing the effect of a pharmacist intervention compared with no pharmacist intervention and reporting on ADEs or PADEs. The risk of bias was assessed using the Cochrane tool for RCTs. A random-effects model was used to pool summary results from individual RCTs.

RESULTS: Fifteen RCTs met the inclusion criteria. The pooled results showed a statistically significant reduction in ADE associated with pharmacist intervention compared with no pharmacist intervention (RR = 0.86; [95% CI 0.80-0.94]; p = 0.0005) but not for PADEs (RR = 0.79; [95% CI 0.47-1.32]; p = 0.37). The heterogeneity was insignificant (I2 = 0%) for ADEs and substantial (I2 = 77%) for PADEs. Patients receiving a pharmacist intervention were 14% less likely for ADE than those who did not receive a pharmacist intervention. The estimated number of patients needed to prevent one ADE across all patient locations was 33.

CONCLUSIONS: To our knowledge, this is the first systematic review and meta-analysis of RCTs seeking to understand the association of pharmacist interventions with ADEs and PADEs. The risk of having an ADE is reduced by a seventh for patients receiving a pharmacist care intervention versus no such intervention. The estimated number of patients needed to be followed across all patient locations to prevent one preventable ADE across all patient locations is 33.

PMID:38973415 | DOI:10.1002/pds.5853

Expert Rev Anticancer Ther. 2024 Jul 5. doi: 10.1080/14737140.2024.2377793. Online ahead of print.

ABSTRACT

OBJECTIVES: Due to its anti-angiogenic properties, trebananib is frequently employed in the treatment of cancer patients, particularly those with ovarian cancer. We conducted a meta-analysis to assess the efficacy and safety profile of trebananib in combination with other drugs for treating both ovarian and non-ovarian cancer patients.

METHODS: Our search encompassed PubMed, Medline, Cochrane, and Embase databases, with a focus on evaluating study quality. Data extraction was conducted from randomized controlled trials (RCTs), and RevMan 5.3 facilitated result analysis.

RESULTS: Combining trebananib with other drugs extended progression-free survival (PFS) [HR 0.81, (95%CI: 0.65, 0.99), p = 0.04] and overall survival (OS) [HR 0.88, (95%CI: 0.79, 1.00), p = 0.04] in ovarian cancer patients. Ovarian cancer patients exhibited a higher objective response rate (ORR) with trebananib compared to non-ovarian cancer cohorts. Moreover, the incorporation of trebananib into the standard treatment regimen for malignant tumors did not significantly elevate drug-related adverse events [RR 1.05, (95% CI: 1.00, 1.11), p = 0.05].

CONCLUSION: Trebananib plus other drugs can improve the PFS, OS and ORR in patients with cancer, especially ovarian cancer. Our recommendation is to use trebananib plus other drugs to treat advanced cancer, and to continuously monitor and manage drug-related adverse events.

REGISTRATION: PROSPERO (No. CRD42023466988).

PMID:38970210 | DOI:10.1080/14737140.2024.2377793

Drug Ther Bull. 2024 Jul 5:dtb-2024-000040. doi: 10.1136/dtb.2024.000040. Online ahead of print.

NO ABSTRACT

PMID:38969481 | DOI:10.1136/dtb.2024.000040

Medicine (Baltimore). 2024 Jul 5;103(27):e38790. doi: 10.1097/MD.0000000000038790.

ABSTRACT

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease characterized by the inflammation and destruction of small blood vessels and circulating ANCAs. Drugs such as antithyroid drugs (ATDs), especially propylthiouracil (PTU), have been used for the production of ANCAs and cause the development of drug-induced AAV. The pathogenesis of this disease is unclear but could be related to the physiological processes affecting the degradation of neutrophil extracellular traps (NETs). At present, PTU is widely used in patients with Graves' disease (GD) who are preparing for pregnancy and whose condition has not been controlled. Once drug-induced AAV has occurred with important organ damage, considering NETs have a significant role in the immune system, whether the cessation of drugs could stop the progression of organ damage is unclear, and a consensus regarding standard treatment has not been established.

PATIENT CONCERNS: In this case report, a female patient who planned pregnancy was hospitalized with multiple joint pain, impaired renal function, and hematuria. Immunofluorescence of the renal biopsy demonstrated spherical and diffuse mesangial distribution of IgA (3+). Autoimmune serology demonstrated positivity for autoantibodies against p-ANCA and an anti-MPO titer 74.72 RU/mL.

DIAGNOSIS: She was diagnosed with PTU-induced p-ANCA-associated and IgA-associated vasculitis (IgAV).

INTERVENTIONS: The patient accepted low doses of glucocorticoid, immunosuppressive therapy and RAI treatment.

OUTCOMES: Both her kidney function and thyroid function remained were on the mend.

CONCLUSION: The authors believe that this type of patient needs to fully consider their pregnancy preparation needs, suspend pregnancy when a small chance of GD remission is indicated, and avoid the use of drugs with reproductive toxicity and other serious adverse events. The multidisciplinary combination therapy of low-dose glucocorticoids and immunosuppressants combined with iodine radiotherapy is one reasonable scheme. At the same time, it is necessary to eliminate the organ damage caused by other reasons. This report provides a clinical treatment basis for patients with drug-induced vasculitis manifestations who cannot receive an accurate diagnosis.

PMID:38968474 | DOI:10.1097/MD.0000000000038790

Ren Fail. 2024 Dec;46(2):2374013. doi: 10.1080/0886022X.2024.2374013. Epub 2024 Jul 5.

ABSTRACT

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning.

METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed.

RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1β were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal.

CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

PMID:38967153 | DOI:10.1080/0886022X.2024.2374013

Acta Clin Croat. 2023 Jul;62(Suppl2):68-75. doi: 10.20471/acc.2023.62.s2.10.

ABSTRACT

Benign prostatic hyperplasia is one of the most common diseases in men, with a prevalence rate of 50% in their 50s to 80% in their 80s, and is mostly treated with chronic drug therapy. The aim of this study was to analyze adverse drug reactions (ADR) to drugs used in benign prostate hyperplasia (BPH) treatment reported to HALMED from 2008 to 2021. Data on ADR reports in Croatia were obtained from the VigiFlow national database and on the use of drugs for BPH in Croatia from Drug Utilization Reports from HALMED. In the observed period, the number of reports on each BPH drug, total number of reports, seriousness of reported ADR, patient age and sex, type of reporter, and most reported ADRs were analyzed. Results showed that 438 ADR reports were received, of which 45.95% on tamsulosin as the most frequently used drug for BPH. Of all reports, 84% were non-serious, 96% were reported in men and 82% in patients older than 45 years. The most frequently reported ADRs were consistent with the known safety profile of BPH drugs. Pharmacists were the most common (47%) reporters of ADRs for BPH drugs, while 33% were reported by physicians. Analysis of the reported ADRs showed that most frequently reported ones were in line with the known safety profile of BPH drugs. However, given the prevalence of the disease and the extent of the use of BPH drugs, it could be argued that the number of reports could be higher (i.e., 34 reports/year). Reporting on ADRs is necessary to better understand the safety profile of drugs in the post-authorization period, and more information on the safe use of medicines could be collected by raising awareness of healthcare professionals.

PMID:38966030 | PMC:PMC11221238 | DOI:10.20471/acc.2023.62.s2.10

Acta Clin Croat. 2023 Jul;62(Suppl2):138-142. doi: 10.20471/acc.2023.62.s2.20.

ABSTRACT

Coagulation disorders in critically ill patients presenting with bleeding can be multicausal. The drugs applied can interfere and impair the coagulation cascade. Point-of-care (POC) coagulation assays may resolve difficult therapeutic situations in critical illness. We report on a 73-year-old critically ill male patient with massive hematuria after bladder lithotripsy. The patient was on low molecular weight heparin therapy due to recent pulmonary embolism. He was subjected to repeated surgical hemostasis which was ineffective despite massive transfusion protocol and normal standard coagulation profile. Additional POC coagulation assays were obtained and were indicative of platelet dysfunction. We revised his medical therapy and suspected the possible drug influence on platelet aggregation. After discontinuation of target drug, platelet aggregation increased whereas hematuria stopped. Coagulation disorders in intensive care unit patients are often multifactorial. Standard laboratory tests are unreliable in complex refractory bleeding and may result in inappropriate therapeutic decisions. Stepwise approach with assessment of clinical parameters, present therapy, and a combination of POC coagulation tests is the key to optimal therapeutic management.

PMID:38966024 | PMC:PMC11221227 | DOI:10.20471/acc.2023.62.s2.20