Anticancer Res. 2023 Feb;43(2):883-891. doi: 10.21873/anticanres.16231.

ABSTRACT

BACKGROUND/AIM: Anemia is one of the dose-limiting toxicities of olaparib. A global randomized controlled trial confirmed that anemia occurrence in Japanese was relatively high. The factors related to anemia in different nationalities remain unknown. Therefore, this study investigated the factors of olaparib-related anemia in real-world settings using an adverse event reporting system database.

PATIENTS AND METHODS: We used data from FDA Adverse Events Reporting System (FAERS) and Japanese Adverse Drug Event Report database (JADER) between 2018 and 2021. FAERS reports from Japan were collected to conduct subgroup analysis, which was defined as FAERS-Japan. The endpoint was the occurrence of olaparib-related anemia. Disproportionality analysis was conducted to calculate reporting odds ratio (ROR), with a confidence interval of 95%. Adjusted ROR (aROR) was calculated to control for sex differences.

RESULTS: In FAERS and JADER, the daily olaparib dose per body weight (DPBW) ≥12 mg/kg was associated with anemia occurrence [aROR; FAERS, 4.483 (3.009-6.680), p<0.001, FAERS-Japan, 1.834 (1.091-3.063), p=0.009, and JADER, 1.628 (1.039-2.551), p=0.034]. Furthermore, FAERS reports confirmed that females with body weight <50 kg, reports from Japan, concomitant use of drugs causing vitamin B12 deficiency, and previous platinum treatment history were associated with olaparib-related anemia. FAERS-Japan also showed that body weight <50 kg and previous platinum treatment history were associated with anemia occurrence.

CONCLUSION: High DPBW constitutes a significant risk of olaparib-related anemia. In addition, information on co-administration of drugs causing vitamin B12 deficiency and previous platinum treatment history is also important for the evaluation of the risk of olaparib-related anemia.

PMID:36697083 | DOI:10.21873/anticanres.16231

Clin Med (Lond). 2023 Jan;23(1):56-60. doi: 10.7861/clinmed.2022-0589.

ABSTRACT

The use of cancer immunotherapies such as immune checkpoint inhibitors (ICIs) has been a paradigm shift in harnessing the immune system to act against cancer cells, and transformed the treatment of several solid and haematological malignancies. Cancer immunotherapies have a unique toxicity profile dependent on their mechanism of action, related to upregulation of immune activity. These can be severe and lead to life-threatening organ toxicity, and therefore identification of at-risk patient groups, early detection and prompt initiation of steroids and other immune-modulating agents is imperative. Acute presentations with toxicity related to these agents comprise a significant proportion of primary and secondary care presentations related to treatment toxicity in oncology. This article will focus on the diagnosis and management of common toxicities associated with immune checkpoint inhibitors, the most commonly utilised cancer immunotherapies.

PMID:36697001 | DOI:10.7861/clinmed.2022-0589

Infect Dis Ther. 2023 Jan 25. doi: 10.1007/s40121-023-00759-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the complement system to trigger a powerful "cytokine and chemokine storm" in viral infection. BDB-001, a recombinant human immunoglobulin G4 (IgG4) that specially binds to C5a, has the potential to inhibit the C5a-triggered cytokine storm in treating COVID-19 patients and other inflammation diseases. Here, we have explored its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adults. This trial is registered with http://www.chinadrugtrials.org.cn/(CTR20200429 ).

METHODS: Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, and 8 mg/kg) and 1 multi-dose cohort (4 mg/kg), and received either BDB-001 or placebo (3:1) double-blindly. The safety and tolerability after administration were evaluated for 21 days for single-dose cohorts and 28 days for the multi-dose cohort. The pharmacokinetics of BDB-001 in plasma and pharmacodynamics as free C5a in plasma were analyzed.

RESULTS: The incidence of drug-related adverse events (AEs) was low, and all AEs were mild or moderate: neither AEs ≥ 3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious adverse events (SAEs) were found. The area under the concentration-time curve from time zero to 480 h (AUC0-480h), that from time zero to infinity (AUCinf), and peak plasma concentration ©max) increased dose-dependently from 2 to 8 mg/kg in the single-dose cohorts and were characterized by a nonlinear pharmacokinetics of target-mediated drug disposal (TMDD). The accumulation index by AUC0-tau after five administrations (4 mg/kg) from the multi-dose cohort was 6.42, suggesting an accumulation effect. Furthermore, inhibition of C5a at the plasma level was observed.

CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.

PMID:36697937 | DOI:10.1007/s40121-023-00759-4

Euro Surveill. 2023 Jan;28(3). doi: 10.2807/1560-7917.ES.2023.28.3.2200195.

ABSTRACT

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3-7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91-0.94 and RI: 0.96; 95% CI: 0.94-0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95-0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00-1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28-1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97-1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.

PMID:36695484 | DOI:10.2807/1560-7917.ES.2023.28.3.2200195

BMJ Open. 2022 Sep 8;12(9):e061457. doi: 10.1136/bmjopen-2022-061457.

ABSTRACT

OBJECTIVE: This study aimed to develop an adverse drug reactions (ADR) antecedent prediction system using machine learning algorithms to provide the reference for security usage of Chinese herbal injections containing Panax notoginseng saponin in clinical practice.

DESIGN: A nested case-control study.

SETTING: National Center for ADR Monitoring and the Electronic Medical Record (EMR) system.

PARTICIPANTS: All patients were from five medical institutions in Sichuan Province from January 2010 to December 2018.

MAIN OUTCOMES/MEASURES: Data of patients with ADR who used Chinese herbal injections containing Panax notoginseng saponin were collected from the National Center for ADR Monitoring. A nested case-control study was used to randomly match patients without ADR from the EMR system by the ratio of 1:4. Eighteen machine learning algorithms were applied for the development of ADR prediction models. Area under curve (AUC), accuracy, precision, recall rate and F1 value were used to evaluate the predictive performance of the model. An ADR prediction system was established by the best model selected from the 1080 models.

RESULTS: A total of 530 patients from five medical institutions were included, and 1080 ADR prediction models were developed. Among these models, the AUC of the best capable one was 0.9141 and the accuracy was 0.8947. According to the best model, a prediction system, which can provide early identification of patients at risk for the ADR of Panax notoginseng saponin, has been established.

CONCLUSION: The prediction system developed based on the machine learning model in this study had good predictive performance and potential clinical application.

PMID:36691200 | PMC:PMC9462100 | DOI:10.1136/bmjopen-2022-061457

BMC Neurol. 2023 Jan 23;23(1):35. doi: 10.1186/s12883-023-03063-3.

ABSTRACT

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive degenerative neuromuscular disease. Nusinersen, with its quick onset of action, can benefit patients early in the treatment course. However, there are currently no clinical studies regarding the improvement in motor function and nutritional status of patients after loading period treatment with nusinersen. Here, we aimed to determine the efficacy of nusinersen in improving motor function and nutritional status in children with SMA treated with nusinersen after loading period in Western China.

METHODS: In this retrospective study, data for all pediatric patients (aged < 18 years), with genetically confirmed diagnosis of SMA who were treated with nusinersen, were collected before initiation of treatment and after 2 months of treatment. We assessed motor function using standardized scales and nutritional status of patients with SMA as well as side effects of nusinersen.

RESULTS: Forty-six pediatric patients aged < 18 years were enrolled in this study. After 2 months of treatment, the motor function of patients with SMA type 1, 2, and 3 improved. The difference in Revised Upper Limb Module scores from M0 to M2 was significant in patients with SMA type 2 and 3 (P = 0.004, P = 0.042, respectively). The difference in Hammersmith Functional Motor Scale Expanded scores from M0 to M2 in patients with SMA type 2 was also significant (P = 0.000). No significant differences were found for Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorder (CHOP-INTEND), Hammersmith Infant Neurologic Examination-Part 2 (HINE-2), and 6-Minute Walking Test (6MWT) scores between M0 and M2, but the scores of CHOP-INTEND, HINE-2, and 6MWT were all increased after loading period treatment. The overall improvement in nutritional status was not statistically significant. No serious adverse effects were observed.

CONCLUSIONS: Our study provides evidence for the efficacy and safety of nusinersen and the nutritional status of pediatric patients with SMA after the loading period treatment. Motor function of all patients improved after 2 months of loading period nusinersen treatment. Patients with a shorter disease duration showed better response to treatment. Careful surveillance of nutritional status is needed in patients with SMA.

PMID:36690929 | DOI:10.1186/s12883-023-03063-3

Pediatr Infect Dis J. 2023 Jan 23. doi: 10.1097/INF.0000000000003832. Online ahead of print.

ABSTRACT

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

METHODS: This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age. The primary objective was safety and tolerability. Key secondary end points included clinical cure and per-participant microbiologic response rates at end of treatment (EOT) and test of cure (TOC) visits.

RESULTS: The microbiologic modified intent-to-treat (mMITT) population included 95 participants (ceftolozane/tazobactam, n = 71; meropenem, n = 24). The most common diagnosis and pathogen were pyelonephritis (ceftolozane/tazobactam, 84.5%; meropenem, 79.2%) and Escherichia coli (ceftolozane/tazobactam, 74.6%; meropenem, 87.5%); 5.7% (ceftolozane/tazobactam) and 4.8% (meropenem) of E. coli isolates were extended-spectrum β-lactamase-producers. Rates of adverse events were similar between treatment groups (any: ceftolozane/tazobactam, 59.0% vs. meropenem, 60.6%; drug-related: ceftolozane/tazobactam, 14.0% vs. meropenem, 15.2%; serious: ceftolozane/tazobactam, 3.0% vs. meropenem, 6.1%). Rates of clinical cure for ceftolozane/tazobactam and meropenem at EOT were 94.4% and 100% and at TOC were 88.7% and 95.8%, respectively. Rates of microbiologic eradication for ceftolozane/tazobactam and meropenem at EOT were 93.0% and 95.8%, and at TOC were 84.5% and 87.5%, respectively.

CONCLUSIONS: Ceftolozane/tazobactam had a favorable safety profile in pediatric participants with cUTI; rates of clinical cure and microbiologic eradication were high and similar to meropenem. Ceftolozane/tazobactam is a safe and effective new treatment option for children with cUTI, especially due to antibacterial-resistant gram-negative pathogens.

PMID:36689671 | DOI:10.1097/INF.0000000000003832

Ann Pharmacother. 2023 Jan 23:10600280221148031. doi: 10.1177/10600280221148031. Online ahead of print.

ABSTRACT

BACKGROUND: Colchicine has a narrow therapeutic index. Its toxicity can be increased due to concomitant exposure to drugs inhibiting its metabolic pathway; these are cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).

OBJECTIVE: To examine clinical outcomes associated with colchicine drug interactions using the spontaneous reports of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

METHODS: We conducted a disproportionality analysis using FAERS data from January 2004 through June 2020. The reporting odds ratio (ROR) and observed-to-expected ratio (O/E) with shrinkage for adverse events related to colchicine's toxicity (ie, rhabdomyolysis/myopathy, agranulocytosis, hemorrhage, acute renal failure, hepatic failure, arrhythmias, torsade de pointes/QT prolongation, and cardiac failure) were compared between FAERS reports.

RESULTS: A total of 787 reports included the combined mention of colchicine, an inhibitor of both CYP3A4 and P-gp drug, and an adverse event of interest. Among reports that indicated the severity, 61% mentioned hospitalization and 24% death. A total of 37 ROR and 34 O/E safety signals involving colchicine and a CYP3A4/P-gp inhibitor were identified. The strongest ROR signal was for colchicine + atazanavir and rhabdomyolysis/myopathy (ROR = 35.4, 95% CI: 12.8-97.6), and the strongest O/E signal was for colchicine + atazanavir and agranulocytosis (O/E = 3.79, 95% credibility interval: 3.44-4.03).

CONCLUSION AND RELEVANCE: This study identifies numerous safety signals for colchicine and CYP3A4/P-gp inhibitor drugs. Avoiding the interaction or monitoring for toxicity in patients when co-prescribing colchicine and these agents is highly recommended.

PMID:36688283 | DOI:10.1177/10600280221148031

J Epilepsy Res. 2022 Dec 30;12(2):68-70. doi: 10.14581/jer.22012. eCollection 2022 Dec.

ABSTRACT

Perampanel is a novel antiepileptic drug that has been used as an adjunctive treatment for focal-onset seizures. No reports to date have documented respiratory suppression as a side effect of perampanel in adults. Herein, we report a 51-year-old man with focal epilepsy presented with type 2 respiratory failure after accidently consuming of 66 mg of perampanel. Clinicians should consider the possibility of respiratory compromise whenever a high dose of perampanel needs to be administered to patients.

PMID:36685743 | PMC:PMC9830032 | DOI:10.14581/jer.22012

Expert Opin Drug Saf. 2023 Jan 23. doi: 10.1080/14740338.2023.2172160. Online ahead of print.

ABSTRACT

BACKGROUND: - The Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS) is a post-marketing surveillance system which relies on spontaneous reports of adverse drug reactions (ADRs). Our objective was to evaluate how black box warning (BBW) updates impact ADR reporting rates.

RESEARCH DESIGN AND METHODS: - We searched MEDWATCH for all BBW updates issued between 01/2014-12/2016 and categorized them as new, major and minor. Rates of relevant ADR reports from the FAERS database in the four years preceding and following a BBW update were assessed amongst the different BBW categories.

RESULTS: - Forty BBW updates were included (16 major, 3 new and 21 minor). A meaningful increase in the proportion of relevant ADRs of all ADRs reported following BBW updates was documented for 53% of new or major updates and 24% of minor updates (p=0.06). The median percentage of reported relevant ADRs increased by 5% following new and major BBW updates and decreased by 30% following minor BBW updates (p=0.3).

CONCLUSIONS: - Reporting of adverse events to the FAERS database is affected by the severity and timing of related BBW updates, highlighting the drawbacks of spontaneous reporting systems. Regulators should promote proactive pharmacovigilance strategies to cope with these limitations.

PMID:36683587 | DOI:10.1080/14740338.2023.2172160

Vaccine. 2023 Jan 23;41(4):922-929. doi: 10.1016/j.vaccine.2022.12.045.

ABSTRACT

Amid the COVID-19 pandemic, the scientific community has been understandably eager to combat misinformation about issues such as vaccine safety. In highly polarized information environments, however, even well-intentioned messages have the potential to produce adverse effects. In this study, we connect different disciplinary strands of social science to derive and experimentally test the novel hypothesis that although particular efforts to debunk misinformation about mRNA vaccines will reduce relevant misperceptions about that technology, these correctives will harm attitudes toward other types of vaccines. We refer to this as the "collateral damage hypothesis." Our study specifically examines a corrective message stating that "mRNA vaccines do not contain live virus," and our results offer some support for our hypothesis, with the corrective triggering increased societal risk perceptions of live vaccines. We also find that the effect is, predictably, most evident among those whose vaccine acceptance is low. Building on the theoretical grounding we outline, we test a "damage control" adjustment to the corrective message and present evidence supporting that it mitigates the collateral damage.

PMID:36682880 | DOI:10.1016/j.vaccine.2022.12.045

J Thorac Oncol. 2023 Feb;18(2):e11-e13. doi: 10.1016/j.jtho.2022.10.012.

NO ABSTRACT

PMID:36682840 | DOI:10.1016/j.jtho.2022.10.012

Auris Nasus Larynx. 2023 Jan 20:S0385-8146(22)00240-1. doi: 10.1016/j.anl.2022.12.012. Online ahead of print.

ABSTRACT

OBJECTIVES: With the COVID-19 pandemic, there is growing interest and research in olfactory and gustatory dysfunction (OGD). Drug-induced dysfunction is an often overlooked etiology. While several medications include smell or taste disturbance as a side effect, there are no publications describing which medications are most frequently implicated. We aim to describe the patterns of these adverse drug reactions (ADRs) using the FDA Adverse Events Reporting System (FAERS).

METHODS: The FAERS database was queried from 2011 to 2021 for terms describing ADRs related to OGD. Terms included anosmia, hyposmia, olfactory test abnormal, olfactory nerve disorder, hallucination olfactory, parosmia, ageusia, hypogeusia, dysgeusia, and taste disorder. We identified the top reported medications associated with general smell dysfunction, general taste dysfunction, reduced smell, and altered smell.

RESULTS: From 2011 to 2021, 16,091 ADRs were reported with OGD, of which13,641 (84.8%) and 2,450 (15.2%) were associated with gustatory and olfactory reactions, respectively. Zinc products (370 reports) and fluticasone propionate (214) were most commonly associated with olfactory dysfunction, specifically reduced olfaction. Varenicline (24) and fluticasone propionate (23) were most commonly associated with altered smell. Lenalidomide (490) and sunitinib (468) were most commonly associated with gustatory dysfunction. Antineoplastic and immunomodulating medications accounted for 21.6% and 36.3% of olfactory and gustatory ADRs, respectively. Among this category, immunoglobulin drugs were the most commonly associated with OGD ADRs.

CONCLUSION: Gustatory dysfunction is more commonly reported ADR compared with olfactory dysfunction. Immunologic/rheumatologic medications are the leading culprit of reported OGD. With increasing numbers of patients presenting to otolaryngologists for OGD, it is important to consider drug-induced etiology.

LEVEL OF EVIDENCE: III.

PMID:36682949 | DOI:10.1016/j.anl.2022.12.012

Eur J Cancer. 2022 Dec 20;181:198-207. doi: 10.1016/j.ejca.2022.12.006. Online ahead of print.

ABSTRACT

AIMS: This study aimed to assess the efficacy and safety of ODX, a novel, cytotoxic, bone-targeting drug candidate, in castration-resistant prostate cancer bone metastatic disease.

METHODS: Patients with progressive disease were randomised to ten cycles of ODX, intravenous infusion Q2W (3, 6, and 9 mg/kg, respectively). The primary objective was to assess the relative change from baseline in bone alkaline phosphatase (B-ALP) and serum-aminoterminal-propeptide of Type I procollagen (S-P1NP) at 12 weeks. The inclusion criteria selected were broad, and a double-blind design was used to ensure objective recruitment of patients for the assessment of efficacy. None of the patients received bone-protecting agents during the ODX treatment period.

RESULTS: Fifty-five 21,20 and 14) patients were randomised to ODX (3, 6 and 9 mg/kg), respectively. The lower number of patients in arm 3 was due to too low a recruitment rate towards the end of the study. The median treatment time were 14, 13 and 14 weeks, respectively. The decrease in B-ALP at 12 weeks in study arms 3, 6 and 9 mg/kg was seen in 6/15 (40%), 8/12 (67%) and 5/12 (42%) patients, respectively, whereas the corresponding numbers for P1NP were 8/15 (53%), 8/12 (67%), and 4/12 (33%), respectively. The median decrease in B-ALP and P1NP at 12 weeks for study arms 3, 6 and 9 mg/kg were 37%, 14% and 43%, respectively, and 51%, 40% and 64%, respectively. The decrease in serum C-terminal telopeptide at 12 weeks was seen in the vast majority of patients and in about one-third of patients in bone scan index. ODX was well tolerated, and no drug-related serious adverse events occurred. There were no significant differences between study arms regarding efficacy and safety.

CONCLUSIONS: ODX was well tolerated and demonstrated inhibitory effects on markers related to the vicious cycle in bone at all three doses. The reduction in metastatic burden, assessed with bone scan index, supports this finding. Studies with continued ODX treatment until disease progression are being planned (ClinicalTrials.gov Identifier: NCT02825628).

PMID:36682096 | DOI:10.1016/j.ejca.2022.12.006

Viruses. 2022 Dec 25;15(1):65. doi: 10.3390/v15010065.

ABSTRACT

As the Corona Disease 2019 (COVID-19) caused by SARS-CoV-2 persists, vaccination is one of the key measures to contain the spread. Side effects (SE) from vaccination are one of the reasons for reluctance to vaccinate. We systematically investigated self-reported SE after the first, second, and booster vaccinations. The data were collected during the TüSeRe: exact study (Tübinger Monitoring Studie zur exakten Analyse der Immunantwort nach Vakzinierung). Employees of health and research institutions were invited to participate. Study participants were asked to fill out an online questionnaire and report their SE after each dose of SARS-CoV-2 vaccination. A total of 1046 participants (mean age: 44 ± 12.9 years; female, n = 815 (78%); male, n = 231 (22%)) were included in the analysis. Local and systemic SE were more frequent after receiving the vector-based vaccine ChAdOx1 nCoV-19 in the first vaccination. However, local and systemic SE were more common after receiving mRNA vaccines (BNT162b2, mRNA-1273) in the second vaccination. Compared to the BNT162b2 vaccine, more SE have been observed after receiving the mRNA-1273 vaccine in the booster vaccination. In multivariate analysis, local and systemic side effects were associated with vaccine type, age and gender. Local and systemic SE are common after SARS-CoV-2 vaccines. The frequency of self-reported local and systemic SE differ significantly between mRNA and vector-based vaccines.

PMID:36680106 | PMC:PMC9864657 | DOI:10.3390/v15010065

Int J Mol Sci. 2023 Jan 16;24(2):1746. doi: 10.3390/ijms24021746.

ABSTRACT

GCSF prophylaxis is recommended in patients on chemotherapy with a &gt;20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10-20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1-2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1-2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1-2 adverse effects and Grade 1-2 immunotherapy-related adverse effects.

PMID:36675262 | PMC:PMC9867035 | DOI:10.3390/ijms24021746

Int J Environ Res Public Health. 2023 Jan 4;20(2):902. doi: 10.3390/ijerph20020902.

ABSTRACT

Many Polish patients do not inform physicians about supplements they use in addition to prescribed medicines. This may be because they consider dietary supplements as being rather natural products that cannot cause health problems. Although dietary supplements may produce side effects, Poland's food safety system and medical statistics do not recognise the necessity of reporting such cases. However, a different approach is observed in France and the United States where adverse effects of food supplements as well as drugs are reported. The aim of this study was to determine the need for creating in Poland a general model of a register monitoring dietary supplements and their adverse effects. In order to achieve this goal, a detailed comparison between the American and European monitoring systems was made. It showed the relationship between negative symptoms caused by specific components in supplements and t profiles of patients who reported side effects. Additionally, it was found that there is a real risk associated with side effects caused by dietary supplements. Therefore, it necessary to establish in Poland a special system for recording such cases as it should be beneficial to patients, including polypragmatic patients.

PMID:36673658 | PMC:PMC9859348 | DOI:10.3390/ijerph20020902

Hepatol Res. 2023 Jan 20. doi: 10.1111/hepr.13883. Online ahead of print.

ABSTRACT

AIM: This study aimed to analyze the current trends of drug-induced liver-related adverse events in the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.

METHODS: The characteristics of implicated drugs were investigated by analyzing big data on drug-induced liver-related adverse events over the past 20 years in FAERS, comparing drug rankings between the JADER and FAERS databases, and calculating rankings of drugs inducing liver-related adverse events using the Medical Dictionary for Regulatory Activities Terminology.

RESULTS: In the 452,272 cases registered in FAERS from 1997 to 2019, warfarin, paracetamol, and adalimumab were the drugs most related to DILI. In the 38,919 cases registered in the JADER from 2004 to 2019, sorafenib, nivolumab, and herbal extracts were the drugs most related to DILI. No associations were found between the top 30 drugs in either of the two databases. Notably, the number of drug-induced liver-related adverse event reports and total adverse events has sharply increased in recent years.

CONCLUSIONS: Although liver-related adverse events are largely caused by host immunity and other constitutional factors, differences in primary diseases, countries, and historical backgrounds lead to differences in the number of reports. Securing an appropriate database and a mechanism to collect real-time information on the frequency of adverse drug reactions is warranted. This article is protected by copyright. All rights reserved.

PMID:36680351 | DOI:10.1111/hepr.13883

Int J Mol Sci. 2023 Jan 6;24(2):1117. doi: 10.3390/ijms24021117.

ABSTRACT

Studies conducted on large populations show a lack of connection between vaccination and serious neurological symptoms. However, there are isolated cases that indicate such a relationship. These reports on adverse effects following immunization (AEFI) reduce social confidence in vaccination; however, their background may be rare genetic defects. The aim of the presented study was to examine if neurological AEFI in children may be associated with variants in genes related to neurodevelopment. To identify such possible associations, a descriptive study of the Polish case series was conducted. We performed next-generation sequencing in patients who, up to 4 weeks of injection of any vaccine, manifested neurological AEFI. We included 23 previously normally developing children with first seizures that occurred after vaccination. We identified pathogenic/likely pathogenic variants in genes engaged in neurodevelopment in nine patients and variants of uncertain significance in another nine patients. The mutated genes belonged to the group of genes related to epilepsy syndromes/epileptic encephalopathy. We showed that AEFI might have a genetic background. We hypothesized that in some AEFI patients, the vaccine might only trigger neurological symptoms that would have been manifested anyway as a result of a pathogenic variant in a gene engaged in neurodevelopment.

PMID:36674629 | DOI:10.3390/ijms24021117

Biomolecules. 2023 Jan 14;13(1):176. doi: 10.3390/biom13010176.

ABSTRACT

Drug-induced liver injury (DILI) is the principal reason for failure in developing drug candidates. It is the most common reason to withdraw from the market after a drug has been approved for clinical use. In this context, data from animal models, liver function tests, and chemical properties could complement each other to understand DILI events better and prevent them. Since the chemical space concept improves decision-making drug design related to the prediction of structure-property relationships, side effects, and polypharmacology drug activity (uniquely mentioning the most recent advances), it is an attractive approach to combining different phenomena influencing DILI events (e.g., individual "chemical spaces") and exploring all events simultaneously in an integrated analysis of the DILI-relevant chemical space. However, currently, no systematic methods allow the fusion of a collection of different chemical spaces to collect different types of data on a unique chemical space representation, namely "consensus chemical space." This study is the first report that implements data fusion to consider different criteria simultaneously to facilitate the analysis of DILI-related events. In particular, the study highlights the importance of analyzing together in vitro and chemical data (e.g., topology, bond order, atom types, presence of rings, ring sizes, and aromaticity of compounds encoded on RDKit fingerprints). These properties could be aimed at improving the understanding of DILI events.

PMID:36671561 | DOI:10.3390/biom13010176