Cancers (Basel). 2023 Mar 14;15(6):1766. doi: 10.3390/cancers15061766.

ABSTRACT

Small molecule protein kinase inhibitors (PKIs) have become an effective strategy for cancer patients. However, hepatotoxicity is a major safety concern of these drugs, since the majority are reported to increase transaminases, and few of them (Idelalisib, Lapatinib, Pazopanib, Pexidartinib, Ponatinib, Regorafenib, Sunitinib) have a boxed label warning. The exact rate of PKI-induced hepatoxicity is not well defined due to the fact that the majority of data arise from pre-registration or registration trials on fairly selected patients, and the post-marketing data are often based only on the most severe described cases, whereas most real practice studies do not include drug-related hepatotoxicity as an end point. Although these side effects are usually reversible by dose adjustment or therapy suspension, or by switching to an alternative PKI, and fatality is uncommon, all patients undergoing PKIs should be carefully pre-evaluated and monitored. The management of this complication requires an individually tailored reappraisal of the risk/benefit ratio, especially in patients who are responding to therapy. This review reports the currently available data on the risk and management of hepatotoxicity of all the approved PKIs.

PMID:36980652 | DOI:10.3390/cancers15061766

Biomedicines. 2023 Mar 6;11(3):798. doi: 10.3390/biomedicines11030798.

ABSTRACT

Atherosclerosis-related coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. This requires effective primary and secondary prevention in reducing the complications related to CAD; the regression or stabilization of the pathology remains the mainstay of treatment. Statins have proved to be the most effective treatment in reducing adverse effects, but there are limitations related to the administration and achievement of effective doses as well as side effects due to the lack of target-related molecular specificity. The implemented technological steps are polymers and nanoparticles for the administration of statins, as it has been seen how the conjugation of drug delivery systems (DDSs) with statins increases bioavailability by circumventing the hepatic-renal filter and increases the related target specificity, enhancing their action and decreasing side effects. Reduction of endothelial dysfunction, reduced intimal hyperplasia, reduced ischemia-reperfusion injury, cardiac regeneration, positive remodeling in the extracellular matrix, reduced neointimal growth, and increased reendothelialization are all drug-related effects of statins enhanced by binding with DDSs. Recent preclinical studies demonstrate how the effect of statins stimulates the differentiation of endogenous cardiac stem cells. Poly-lactic-co-glycolic acid (PLGA) seems to be the most promising DDS as it succeeds more than the others in enhancing the effect of the bound drug. This review intends to summarize the current evidence on polymers and nanoparticles for statin delivery in the field of cardiovascular disease, trying to shed light on this topic and identify new avenues for future studies.

PMID:36979777 | DOI:10.3390/biomedicines11030798

Biomolecules. 2023 Feb 21;13(3):405. doi: 10.3390/biom13030405.

ABSTRACT

Drug abuse is a worldwide problem that leads to negative physical, mental, and economic consequences. Although pharmacological strategies for drug addiction management have been widely studied, therapeutic options with high efficacy and a low side-effects profile are still limited. Recently, there has been a growing interest in oxytocin (OT) and vasopressin (AVP) systems as potential therapeutic targets for the treatment of drug abuse. OT and AVP are hypothalamic neuropeptides involved in numerous physiological processes. Additionally, studies show that these neurohormones are highly implicated in the modulation of a wide range of behaviors. Interestingly, ample evidence has shown that both, OT and AVP are able to decrease the consumption of different drugs of abuse, as well as to ameliorate their rewarding and reinforcing effects. Furthermore, OT and AVP have been strongly involved in prosocial effects and social reward. In particular, OT has been shown to be able to shift drug-induced reward into social-induced reward, mainly due to its interaction with the dopaminergic system. This phenomenon is also reflected in the results of clinical trials where intranasal OT shows promising efficacy in managing substance use disorder. Therefore, the aim of this review is to comprehensively characterize the involvement of OT and AVP in the rewarding and other behavioral effects of drugs of abuse in animal models, with a particular highlight on the impact of social factors on the observed effects. Understanding this relationship may contribute to higher drug development success rates, as a result of a more profound and deliberate studies design.

PMID:36979340 | DOI:10.3390/biom13030405

Drug Des Devel Ther. 2023 Mar 21;17:851-861. doi: 10.2147/DDDT.S402362. eCollection 2023.

ABSTRACT

Tapentadol is an analgesic compound that acts centrally to attenuate pain. Previous studies have shown that tapentadol has dual mechanisms of action as a mu-opioid receptor agonist and noradrenaline re-uptake inhibition. Therefore, tapentadol provides a great advantage over classic opioids in pain management from nociceptive to neuropathic. Cumulative evidence from in vitro data suggests that tapentadol effect of norepinephrine re-uptake could be a new target that overcomes other classic opioids in chronic neuropathic pain. Compared to tramadol and other opioids, tapentadol is associated with fewer adverse effects than tramadol. Tapentadol is a new alternative to treat acute, chronic, and neuropathic pain. Thus, this review article was focused on understanding the studies that led to the development of tapentadol as a novel analgesic drug and its advantages over conventional opioids. Thus, tapentadol is a good alternative with fewer adverse effects and is available for human use.

PMID:36974332 | PMC:PMC10039632 | DOI:10.2147/DDDT.S402362

Hypertens Res. 2023 Mar 28. doi: 10.1038/s41440-023-01260-8. Online ahead of print.

ABSTRACT

Although renin-angiotensin system (RAS) inhibitors reduce the risk of cardiovascular diseases and end-stage kidney disease (ESKD) in chronic kidney disease (CKD) patients, they are often discontinued in clinical practice due to drug-related adverse events. However, limited evidence is available about the clinical impact of RAS inhibitor discontinuation in CKD patients. A comprehensive search of publications investigating the effect of discontinuing RAS inhibitors on clinical outcomes in CKD patients in PubMed, the Cochrane Library, and Web of Science was conducted (inception to November 7, 2022), and potentially relevant studies were searched by hand (through November 30, 2022). Two reviewers independently extracted data according to the PRISMA and MOOSE guidelines and assessed the quality of each study with risk-of-bias tools, RoB2 and ROBINS-I. The pooled hazard ratio (HR) for each outcome was integrated with a random-effect model. A total of 1 randomized clinical trial and 6 observational studies involving 248,963 patients were included in the systematic review. The meta-analysis of observational studies showed that discontinuation of RAS inhibitors was associated with a higher risk of all-cause mortality (HR, 1.41 [95% CI, 1.23-1.62]; I2 = 97%), ESKD (1.32 [95% CI, 1.10-1.57]; I2 = 94%) and MACE (1.20 [95% CI 1.15-1.25]; I2 = 38%), but not with hyperkalemia (0.79 [95% CI 0.55-1.15]; I2 = 90%). Overall risk of bias was moderate-to-serious, and quality of evidence (GRADE system) was low-to-very low. The present study suggests that CKD patients would benefit from continuing RAS inhibitors.

PMID:36977900 | DOI:10.1038/s41440-023-01260-8

Int J Clin Pharm. 2023 Mar 28. doi: 10.1007/s11096-023-01564-2. Online ahead of print.

ABSTRACT

BACKGROUND: Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results.

AIM: The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development.

METHOD: Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage.

RESULTS: There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43-1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24-4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05-2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35-2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16-1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium.

CONCLUSION: Our study's findings suggest that antiepileptic drug usage may be associated with delirium development.

PMID:36977859 | DOI:10.1007/s11096-023-01564-2

Diabetes Obes Metab. 2023 Mar 27. doi: 10.1111/dom.15064. Online ahead of print.

ABSTRACT

AIM: To report a Phase I study of subcutaneous glucagon receptor (GCGR)/glucagon-like peptide 1 receptor (GLP-1R) dual agonist BI 456906 versus placebo in healthy Japanese men with overweight/obesity.

MATERIALS AND METHODS: We investigated multiple rising doses of BI 456906 escalated over 16 weeks (maximum doses: 1.8 mg once weekly [qw; dose group (DG) 1], 4.8 mg qw [DG 2] and 2.4 mg twice weekly [DG 3]) in Japanese men with a body mass index of 23-40 kg/m2 .

RESULTS: Thirty-six participants were treated (n=9 per DG and placebo). Overall, 10 participants (37.0%) treated with BI 456906 withdrew from dose escalation; all due to adverse events (amylase increase, n=1; decreased appetite, n=9), and the proportion of participants was higher in DG 2 (n=6, 66.7%) versus DGs 1 and 3 (both n=2, 22.2%). No participants receiving placebo withdrew from dose escalation. BI 456906 exposure increased with dose and dose escalation in each DG. Treatment with BI 456906 decreased placebo-corrected bodyweight after 16 weeks (placebo +1.06%): DG 1, -5.57%; DG 2, -12.37%; DG 3, -9.62%. Paracetamol absorption decreased in Week 1 for DGs 2 and 3, indicating transient delayed gastric emptying. BI 456906 reduced plasma alanine and glucagon levels, indicating indirect target engagement at GCGRs and GLP-1Rs. Drug-related adverse events were reported for all participants receiving BI 456906 and four receiving placebo; most frequently decreased appetite (n=24, 66.7%).

CONCLUSIONS: BI 456906 showed no unexpected tolerability concerns and reduced placebo-corrected bodyweight by up to 12.37% in Japanese men with overweight/obesity after 16 weeks' treatment. This article is protected by copyright. All rights reserved.

PMID:36974349 | DOI:10.1111/dom.15064

Br J Haematol. 2023 Mar 27. doi: 10.1111/bjh.18772. Online ahead of print.

ABSTRACT

Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28-day cycles of pomalidomide 4 mg daily on days 1-21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow-up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression-free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug-related non-haematological AEs (>5%) comprised 13% infections. Long-term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response.

PMID:36974007 | DOI:10.1111/bjh.18772

BMC Med Res Methodol. 2023 Mar 27;23(1):71. doi: 10.1186/s12874-023-01885-w.

ABSTRACT

BACKGROUND: Drug toxicity does not affect patients equally; the toxicity may only exert in patients who possess certain attributes of susceptibility to specific drug properties (i.e., drug-host interaction). This concept is crucial for personalized drug safety but remains under-studied, primarily due to methodological challenges and limited data availability. By monitoring a large volume of adverse event reports in the postmarket stage, spontaneous adverse event reporting systems provide an unparalleled resource of information for adverse events and could be utilized to explore risk disparities of specific adverse events by age, sex, and other host factors. However, well-formulated statistical methods to formally address such risk disparities are currently lacking.

METHODS: In this paper, we present a statistical framework to explore spontaneous adverse event reporting databases for drug-host interactions and detect risk disparities in adverse drug events by various host factors, adapting methods for safety signal detection. We proposed four different methods, including likelihood ratio test, normal approximation test, and two tests using subgroup ratios. We applied our proposed methods to simulated data and Food and Drug Administration (FDA) Adverse Event Reporting Systems (FAERS) and explored sex-/age-disparities in reported liver events associated with specific drug classes.

RESULTS: The simulation result demonstrates that two tests (likelihood ratio, normal approximation) can detect disparities in adverse drug events associated with host factors while controlling the family wise error rate. Application to real data on drug liver toxicity shows that the proposed method can be used to detect drugs with unusually high level of disparity regarding a host factor (sex or age) for liver toxicity or to determine whether an adverse event demonstrates a significant unbalance regarding the host factor relative to other events for the drug.

CONCLUSION: Though spontaneous adverse event reporting databases require careful data processing and inference, the sheer size of the databases with diverse data from different countries provides unique resources for exploring various questions for drug safety that are otherwise impossible to address. Our proposed methods can be used to facilitate future investigation on drug-host interactions in drug toxicity using a large number of reported adverse events.

PMID:36973693 | DOI:10.1186/s12874-023-01885-w

Intern Med J. 2023 Mar;53(3):454. doi: 10.1111/imj.16028.

NO ABSTRACT

PMID:36972987 | DOI:10.1111/imj.16028

JAMA Netw Open. 2023 Mar 1;6(3):e234732. doi: 10.1001/jamanetworkopen.2023.4732.

ABSTRACT

IMPORTANCE: Uptake of vaccination against COVID-19 is strongly affected by concerns about adverse effects. Research on nocebo effects suggests that these concerns can amplify symptom burden.

OBJECTIVE: To investigate whether positive and negative expectations prior to COVID-19 vaccination are associated with systemic adverse effects.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed the association of expected benefits and risks of vaccination, adverse effects at first vaccination, and observed adverse effects in close contacts with severity of systemic adverse effects among adults receiving a second dose of messenger RNA (mRNA)-based vaccines between August 16 and 28, 2021. A total of 7771 individuals receiving the second dose at a state vaccination center in Hamburg, Germany, were invited to participate; of these, 5370 did not respond, 535 provided incomplete information, and 188 were excluded retrospectively. The mobile application m-Path was used for data collection.

MAIN OUTCOMES AND MEASURES: Primary outcome was a composite severity index of systemic adverse effects in 12 symptom areas measured once daily with an electronic symptom diary over 7 consecutive days. Data were analyzed by mixed-effects multivariable ordered logistic regression adjusted for prevaccine symptom levels and observation times.

RESULTS: A total of 10 447 observations from 1678 individuals receiving vaccinations (BNT162b2 [Pfizer BioNTech] in 1297 [77.3%] and mRNA-1273 [Moderna] in 381 [22.7%]) were collected. The participants' median age was 34 (IQR, 27-44) years, and 862 (51.4%) were women. The risk for more severe adverse effects was higher for persons expecting a lower benefit of vaccination (odds ratio [OR] for higher expectations, 0.72 [95% CI, 0.63-0.83]; P < .001), expecting higher adverse effects of vaccination (OR, 1.39 [95% CI, 1.23-1.58]; P < .001), having experienced higher symptom burden at the first vaccination (OR, 1.60 [95% CI, 1.42-1.82]; P < .001), scoring higher on the Somatosensory Amplification Scale (OR, 1.21 [95% CI, 1.06-1.38]; P = .004), and if the vaccine mRNA-1273 was given rather than BNT162b2 (OR, 2.45 [95% CI, 2.01-2.99]; P < .001). No associations were seen for observed experiences.

CONCLUSIONS AND RELEVANCE: In this cohort study, several nocebo effects occurred in the first week after COVID-19 vaccination. The severity of systemic adverse effects was associated not only with vaccine-specific reactogenicity but also more negative prior experiences with adverse effects from the first COVID-19 vaccination, more negative expectations regarding vaccination, and tendency to catastrophize instead of normalize benign bodily sensations. Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines.

PMID:36972051 | PMC:PMC10043751 | DOI:10.1001/jamanetworkopen.2023.4732

Support Care Cancer. 2023 Mar 27;31(4):235. doi: 10.1007/s00520-023-07688-5.

ABSTRACT

PURPOSE: Chemotherapy-related polyneuropathy (CIPN) is a very common, often dose-limiting side effect that affects the patients' quality of life. Treatment usually consists of a combination of medicinal, medical, and individualized treatment approaches, although the effectiveness of these therapies is insufficient for many patients. The aim of this article is to review and evaluate the impact of CIPN on patients' daily lives and possible effective treatment approaches.

METHODS: A standardized questionnaire was developed based on ten anonymous telephone interviews with CIPN patients. The content of the questionnaire was divided into 5 categories: demographics, clinical presentation, everyday symptoms, treatment of CIPN symptoms, and medical care. Mostly closed questions were used but multiple choice and individual additions by free text answers were possible.

RESULTS: CIPN limits patients' quality of life over a long period of time. In addition to diurnal and situational fluctuations, the emotional burden negatively affects patients' daily lives in many ways. From the patients' point of view, the individually implemented therapy measures were most effective in treating their complaints. But even the combination of different therapy methods insufficiently alleviates the symptoms of the patients.

CONCLUSION: It is important and necessary to comprehensively inform patients about CIPN as a possible side effect, to point out prevention strategies, and to critically examine and evaluate different therapy approaches. In this way, misunderstandings of the doctor-patient relationship can be avoided. In addition, patient satisfaction and quality of life can be increased in the long term.

PMID:36971861 | PMC:PMC10042917 | DOI:10.1007/s00520-023-07688-5

Pak J Pharm Sci. 2023 Jan;36(1):31-38.

ABSTRACT

The goal of this research was to determine whether the combination of baicalein (BL) and losartan (LT) would provide greater protection against DOX-induced nephrotoxicity. There were five groups of male rats in the experiment: the 1) control, 2) DOX, 3) DOX+LT, 4) DOX+BL and 5) DOX+LT+BL groups. A dose of DOX was administered following two weeks of LT and BL therapy. In the DOX-affected group, serum renal indicators, including creatinine and urea, rose considerably compared to those in the control groups (p<0.01). Further, there was a statistically significant increase (p<0.001) in the levels of the cytokines that promote inflammation in renal tissue, including tumor necrosis factor-α, interleukin (IL)-1 and IL-6. In addition, the level of the anti-inflammatory cytokine IL-10 decreased significantly (p<0.001) in the DOX-challenged group compared to the control groups. In addition, renal cell indicators of oxidative stress (p<0.001) and enzymatic activity (p<0.01) reduced dramatically in the DOX-challenged group, whereas renal cell thiobarbituric acid retroactive materials rose greatly (p<0.001). Finally, the DOX group had higher kidney protein expression and inflammatory activity than the control groups (p<0.001). The combination of BL and LT therapy protected DOX-challenged rats via antioxidant and anti-inflammatory activities.

PMID:36967494

Front Med (Lausanne). 2023 Mar 8;10:1027589. doi: 10.3389/fmed.2023.1027589. eCollection 2023.

ABSTRACT

Dupilumab was the first biological medication licensed to treat atopic dermatitis (AD), and it has shown remarkable effectiveness and safety in the treatment of moderate-to-severe atopic dermatitis. There are limited drug-related adverse events associated with dupilumab in atopic dermatitis (AD) treatment. Here, we present two cases of local Staphylococcus aureus infection during the treatment of atopic dermatitis with dupilumab.

PMID:36968828 | PMC:PMC10031056 | DOI:10.3389/fmed.2023.1027589

JHEP Rep. 2023 Feb 15;5(5):100699. doi: 10.1016/j.jhepr.2023.100699. eCollection 2023 May.

ABSTRACT

BACKGROUND & AIMS: The aim of the study was to evaluate the efficacy and safety of adjuvant sorafenib treatment compared with placebo in patients with hepatocellular carcinoma who underwent local ablation.

METHODS: The SORAMIC trial is a randomised controlled trial with diagnostic, local ablation, and palliative sub-study arms. After initial imaging within the diagnostic study, patients were assigned to local ablation or palliative arms. In the local ablation cohort, patients were randomised 1:1 to local ablation + sorafenib vs. local ablation + placebo. The primary endpoint was time-to-recurrence (TTR). Secondary endpoints were local control rate and safety in terms of adverse events and quality-of-life.

RESULTS: The recruitment was terminated prematurely after 104 patients owing to slow recruitment. One patient was excluded because of a technical failure. Fifty-four patients were randomised to local ablation + sorafenib and 49 to local ablation + placebo. Eighty-eight patients who underwent standardised follow-up imaging comprised the per-protocol population. The median TTR was 15.2 months in the sorafenib arm and 16.4 months in the placebo arm (hazard ratio 1.1; 95% CI 0.53-2.2; p = 0.82). Out of 136 lesions ablated within the trial, there was no difference in local recurrence rate between sorafenib (6/69, 8.6%) and placebo groups (5/67, 5.9%; p = 0.792).Overall (92.5% vs. 71.4%, p = 0.008) and drug-related (81.4% vs. 55.1%, p = 0.003) adverse events were more common in the sorafenib arm compared with the placebo arm. Dose reduction because of adverse events were common in the sorafenib arm (79.6% vs. 30.6%, p <0.001).

CONCLUSIONS: Adjuvant sorafenib did not improve in TTR or local control rate after local ablation in patients with hepatocellular carcinoma within the limitations of an early terminated trial.

IMPACT AND IMPLICATIONS: Local ablation is the standard of care treatment in patients with early stages of hepatocellular carcinoma, along with surgical therapies. However, there is a risk of disease recurrence during follow-up. Sorafenib, an oral medication, is a routinely used treatment for patients with advanced hepatocellular carcinoma. This study found that sorafenib treatment after local ablation in people with early hepatocellular carcinoma did not significantly improve the disease-free period compared with placebo.

CLINICAL TRIAL NUMBER: EudraCT 2009-012576-27, NCT01126645.

PMID:36968218 | PMC:PMC10031000 | DOI:10.1016/j.jhepr.2023.100699

Oncology (Williston Park). 2023 Mar 21;37(3):130-141. doi: 10.46883/2023.25920987.

ABSTRACT

BACKGROUND: Mitogen-activated protein kinase (MEK) inhibitors, which integrate the important signaling chain of the RAS-RAF-MEK-ERK1/2 pathway, regulate cell functions such as division and proliferation for patients with solid tumors. However, various ocular adverse effects (AEs) affect patients during clinical treatment. This systematic review aimed to assess the occurrence of AEs during treatment with MEK inhibitors plus targeted therapy or chemotherapy.

METHODS: A scientific literature search was conducted in PubMed, the Cochrane Library, Embase, and several Chinese databases to identify randomized controlled trials. Overall, ocular AEs were assessed as the primary end point; blurred vision, chorioretinopathy, and retinal detachment were assessed as secondary end points.

RESULTS: Seventeen randomized controlled trials were included. Overall, the use of MEK inhibitors combined with other targeted inhibitors or chemotherapy was significantly associated with a nearly 7.3% increased risk of overall ocular toxicities vs therapy without MEK inhibitors (risk ratio [RR], 2.88; 95% CI, 1.42-5.85, P < .05). An increased risk of blurred vision (RR, 4.10; 95% CI, 2.55- 6.58; P < .05), chorioretinopathy (RR, 8.36; 95% CI, 3.42-20.47; P < .05), and retinal detachment (RR, 8.98; 95% CI, 3.92-20.57; P < .05) was demonstrated.

CONCLUSIONS: Treatment with MEK inhibitors combined with targeted drugs or chemotherapy seems to increase overall ocular AEs. A more practical algorithm for the screening of ocular AEs was suggested to be conducted whenever new or worsening ocular toxicities occur.

PMID:36961957 | DOI:10.46883/2023.25920987

Front Immunol. 2023 Mar 7;14:1117447. doi: 10.3389/fimmu.2023.1117447. eCollection 2023.

ABSTRACT

BACKGROUND: Cancer is concerning owing to its high mortality rate. Consequently, methods of prolonging the life of patients with cancer have become the primary focus of attention research. In recent years, immune checkpoint inhibitors (ICIs) have achieved good clinical efficacy as antitumor drugs; however, their severe adverse effects have made their use challenging. In order to clarify the predictors of adverse effects, scientists have conducted a series of studies. Blood counts can potentially monitor risk factors associated with the occurrence of immune-related adverse events (irAEs). Herein, a meta-analysis was performed to clarify further the guiding significance of blood counts in the clinical setting.

METHODS: Studies that satisfied the inclusion criteria were obtained by searching the database. Included studies were those in which irAEs had been observed, and evidence of an association between blood counts and irAEs was reported. The included ones were evaluated for quality. In addition to sensitivity analysis and subgroup analysis, a meta-analysis was performed using the odds ratio (OR) and 95% confidence interval (CI) for each study.

RESULTS: A total of 18 articles were included in our study. The analyses were performed separately according to different blood cell count indicators. The blood cell count metrics associated with irAEs were: absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio.

CONCLUSION: Our review and meta-analysis of studies suggest that absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio may serve as predictors of the emergence of irAEs. Given the small number of studies focusing on the relationship between patient blood cell counts and the risk of irAEs, future studies need to further explore the mechanisms of occurrence and potential associations.

PMID:36960068 | PMC:PMC10029759 | DOI:10.3389/fimmu.2023.1117447

Pharmacol Res Perspect. 2023 Apr;11(2):e01077. doi: 10.1002/prp2.1077.

ABSTRACT

Spontaneous reporting is based on the experience of all healthcare professionals (HCPs) but also consumers/non-HCPs and therefore reveals a broad picture of a drug's adverse reactions. Recent studies found substantial differences between reports from these varying sources including the reports' completeness. Using the example of opioid-associated abuse, dependence, or withdrawal, this study analyzed the completeness and characteristics of spontaneous reports from Germany focusing on the reporter. Based on EudraVigilance data, we included all cases of abuse, dependence, or withdrawal associated with opioids indicated for pain therapy and filed from Germany until 2018. Completeness and characteristics were analyzed by a reporter (physician, pharmacist, other HCPs, consumers/non-HCPs) and also by time period to account for other influencing factors. In total, 1721 cases were included, mainly filed by physicians (38.5%) and pharmacists (30.7%). Completeness of demographics varied from 74.5% (other HCPs) to 42.7% (consumers/non-HCPs). Consumers/non-HCPs most often provided any indication/comorbidity (75.2%), whereas this was the case for only 20.2% of pharmacists. Large differences between the reporters were found for almost all characteristics. Other HCPs far more often coded a history of drug abuse, dependence, or withdrawal than other reporters (46.9% vs. 11.6%-24.2%, respectively), and fatal outcomes were also mainly filed by other HCPs (68.1% vs. 14.8%-20.4% by all other reporters). Differences in completeness and characteristics were also observed over time. Studies analyzing spontaneous data should consider potential differences between the various reporting groups in terms of completeness and characteristics. Further, the impact of other influencing factors has to be assessed.

PMID:36959713 | PMC:PMC10036728 | DOI:10.1002/prp2.1077

Diagn Interv Radiol. 2023 Jan 31;29(1):80-90. doi: 10.5152/dir.2022.21614. Epub 2022 Nov 29.

ABSTRACT

Pulmonary adverse events and drug-induced lung disease (DILD) can occur when treating many conditions. The incidence of DILDs in clinical practice and the variety of radiological findings have increased, mainly due to the increased use of novel therapeutic agents. It is crucial to determine whether the newly emerging clinical and imaging findings in these patients are due to the progression of the underlying disease, infection, pulmonary edema, or drug use, as this will change the patient management. Although the diagnosis of DILD is usually obtained by excluding other possible causes, radiologists should be aware of the imaging findings of DILD. This article reviews the essential radiological results of DILD and summarizes the critical clinical and imaging findings with an emphasis on novel therapeutic agents.

PMID:36960496 | DOI:10.5152/dir.2022.21614

Eye (Lond). 2023 Mar 23. doi: 10.1038/s41433-023-02505-z. Online ahead of print.

ABSTRACT

PURPOSE: Assess short-term real-world outcomes in neovascular aged-related macular degeneration (nAMD) treated with novel faricimab.

METHODS: Retrospective case series of nine patients with nAMD (11 eyes) treated with faricimab between May and November 2022. Treatment-naïve patients and non-naïve patients underwent logMAR best corrected visual acuity (BCVA), optical coherence tomography (OCT) DRI OCT-1 Triton (Topcon Corp, Tokyo, Japan), ultra-widefield (UWF) and fundus autofluorescence (FAF) (California Optomap, Optos plc, Dunfermline, Scotland, UK). Previous treatment intervals, number of intravitreal injections, sub/intra retinal fluid (SRF/IRF), central retinal thickness (CRT) and presence/changes in pigment epithelial detachments (PEDs) were recorded.

RESULTS: Mean baseline BCVA and CRT values of patients who switched from other agents were 0.612 ± 0.75 logMAR and 256.16 ± 12.98 µm respectively, with a mean 36-day previous treatment interval. The median number of other previous anti-VEGF intravitreal injections was 8. Mean BCVA at one month significantly improved to 0.387 ± 0.54 logMAR, as well as CRT values which decreased to 245.43 ± 15.34 µm. In the 3 naïve patients, mean baseline BVCA and CRT values were 0.33 ± 0.29 and 874.67 ± 510.86 µm, respectively. At one month follow-up, mean BCVA improved to 0.30 ± 0.29 logMAR and mean CRT was 536.04 ± 36.15 µm. Overall, a significant improvement in BCVA of 0.21 ± 41 logMAR and 238.44 ± 114.9 µm was achieved at one month after the first faricimab intravitreal injection. In addition, a complete resolution of SRF was observed in 6 out of 8 eyes (75%) and of IRF in 2 out of 3 eyes (66.67%), respectively. Drusenoid PED morphology changes were observed in all patients and no drug-related adverse events were observed.

CONCLUSION: Real-world outcomes showed improvement in BCVA and anatomic parameters at an early timepoint, demonstrating the efficacy and durability of faricimab in nAMD patients. Larger numbers of patients and longer follow-up are needed to determine whether the loading dose is required in all, what percentage of patients experience an improvement, and whether improvement it is maintained.

PMID:36959312 | DOI:10.1038/s41433-023-02505-z