iScience. 2024 Sep 10;27(10):110916. doi: 10.1016/j.isci.2024.110916. eCollection 2024 Oct 18.

ABSTRACT

Genetic ancestry plays a major role in pharmacogenomics, and a deeper understanding of the genetic diversity among individuals holds immerse promise for reshaping personalized medicine. In this pivotal study, we have conducted a large-scale genomic analysis of 1,136 pharmacogenomic variants employing machine learning algorithms on 3,714 individuals from publicly available datasets to assess the risk proximity of experiencing drug-related adverse events. Our findings indicate that Admixed Americans and Europeans have demonstrated a higher risk of experiencing drug toxicity, whereas individuals with East Asian ancestry and, to a lesser extent, Oceanians displayed a lower risk proximity. Polygenic risk scores for drug-gene interactions did not necessarily follow similar assumptions, reflecting distinct genetic patterns and population-specific differences that vary depending on the drug class. Overall, our results provide evidence that genetic ancestry is a pivotal factor in population pharmacogenomics and should be further exploited to strengthen even more personalized drug therapy.

PMID:39391720 | PMC:PMC11465127 | DOI:10.1016/j.isci.2024.110916

Bull Emerg Trauma. 2024;12(3):103-110. doi: 10.30476/beat.2024.102203.1503.

ABSTRACT

OBJECTIVE: The present study aimed to evaluate the clinical benefits and drawbacks of administering ECMO/ECLS therapies to drug-intoxicated patients.

METHODS: From inception until April 30, 2024, an extensive search was performed on four main databases: PubMed, Web of Science, Cochrane Library, and EMBASE. There was no restriction on the search period. Only the studies that reported survival to hospital discharge rates, adverse events, and the utilization of ECMO/ECLS in the treatment of intoxicated patients were included. On the other hand, articles that did not report adverse events or hospital discharge rates as outcomes, as well as studies published in languages other than English, were excluded. The evaluated outcomes were the rate of survival to hospital discharge rate and the incidence of adverse events associated with ECMO therapy. The Newcastle Ottawa scale was employed to appraise each study to determine its methodological quality. The Comprehensive Meta-Analysis (CMA) software (version 3.0) for statistical analysis was used, with the random effects model (due to high heterogeneity among the studies) and a 95% confidence interval.

RESULTS: From a total search of 2216 search results, only 10 studies were included. The pooled analysis from 10 studies indicated that ECMO therapies among drug-overdosed/poisoned patients were associated with a significant survival to hospital discharge rate of 65.6% ([95% CI: 51.5%-77.4%], p=0.030). However, the outcomes were highly heterogeneous (I2=83.47%), which could be attributed to the use of several medicines by different studies. In contrast, ECMO therapies among drug-overdosed patients were associated with a significant incidence rate of adverse events of 23.1% ([95% CI: 12.3%-39.2%], p=0.002). However, the pooled analysis had a significant heterogeneity (I2=70.27%).

CONCLUSION: Despite various health complications, extracorporeal membrane treatment enhanced survival to hospital discharge with good neurological outcomes. Hence, it was a viable, effective, and feasible alternative for managing drug-induced intoxication in patients.

PMID:39391356 | PMC:PMC11462113 | DOI:10.30476/beat.2024.102203.1503

Drug Des Devel Ther. 2024 Oct 5;18:4471-4480. doi: 10.2147/DDDT.S466603. eCollection 2024.

ABSTRACT

PURPOSE: This study aimed to estimate the effect of different doses of fentanyl on the median effective dose (ED50) of ciprofol for attenuating the airway and motor response to laryngeal mask airway (LMA) insertion response in healthy children.

PATIENTS AND METHODS: 90 healthy preschool patients undergoing inguinal hernia repair surgery were randomly assigned to one of three groups: C0 (ciprofol+saline), C1 (ciprofol + fentanyl 1µg/kg), C2 (ciprofol + fentanyl 2µg/kg). Anesthesia was induced with either prepared fentanyl or saline, followed by ciprofol. The dose of ciprofol for each patient was determined using the up-and-down sequential study design. The primary outcome was the ED50 of ciprofol required for smooth LMA insertion in the three groups. Additionally, the time to loss of consciousness and any perioperative adverse events were recorded.

RESULTS: Compared with the C0 group, the ED50 (95% confidence interval) of ciprofol in the C1 and C2 groups were significantly lower (1.81 [1.73-1.90]mg/kg versus 0.67 [0.64-0.71]mg/kg and 0.48 [0.42-0.54] mg/kg, respectively; P<0.05). Additionally, the ED50 of ciprofol in the C2 group was lower than that in the C1 group (0.42 [0.42-0.54] mg/kg vs 0.67 [0.64-0.71]mg/kg; P<0.05). Furthermore, the time to loss of consciousness in the C1 and C2 groups decreased by 60% and 53%, respectively, compared to the C0 group. There were no significant differences in the incidence of drug-related hypotension after anesthesia induction among the three groups. No adverse events of hypoxia, bradycardia, or injection pain were observed in any groups.

CONCLUSION: In healthy, non-obese Chinese children undergoing elective inguinal hernia repair surgery, fentanyl 1 µg/kg and 2 µg/kg before ciprofol injection significantly reduced the ED50 of ciprofol for attenuating LMA response, with minimal occurrence of severe side effects.

PMID:39391355 | PMC:PMC11464411 | DOI:10.2147/DDDT.S466603

Eur J Hosp Pharm. 2024 Oct 10:ejhpharm-2024-004365. doi: 10.1136/ejhpharm-2024-004365. Online ahead of print.

NO ABSTRACT

PMID:39389767 | DOI:10.1136/ejhpharm-2024-004365

Drug Ther Bull. 2024 Oct 10:dtb-2024-000061. doi: 10.1136/dtb.2024.000061. Online ahead of print.

NO ABSTRACT

PMID:39389760 | DOI:10.1136/dtb.2024.000061

Br J Pharmacol. 2024 Oct 10. doi: 10.1111/bph.17358. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Irwin tests are key preclinical study elements for characterising drug-induced neurological side effects. This multicentre study aimed to assess the robustness of Irwin tests across multinational sites during three stages of protocol harmonisation. The projects were part of the Enhanced Quality in Preclinical Data framework, aiming to increase success rates in transition from preclinical testing to clinical application.

EXPERIMENTAL APPROACH: Female and male NMRI mice were assigned to one of three groups (vehicle, MK-801 0.1 and 0.3 mg kg-1). Irwin scores were assessed at baseline and multiple times following intraperitoneal injection of MK-801 using local protocols (Stage 1), shared protocols with harmonised environmental design (Stage 2) and fully harmonised Irwin scoring protocols (Stage 3).

KEY RESULTS: The analysis based on the four functional domains (motor, autonomic, sedation and excitation) revealed substantial data variability in Stages 1 and 2. Although there was still marked overall heterogeneity between sites in Stage 3 after complete harmonisation of the Irwin scoring scheme, heterogeneity was only moderate within functional domains. When comparing treatment groups versus vehicle, we found large effect sizes in the motor domain and subtle to moderate effects in the excitation-related and autonomic domains.

CONCLUSION AND IMPLICATIONS: The pronounced interlaboratory variability in Irwin datasets for the CNS-active compound MK-801 needs to be carefully considered when making decisions during drug development. While environmental and general study design had a minor impact, the study suggests that harmonisation of parameters and their scoring can limit variability and increase robustness.

PMID:39389585 | DOI:10.1111/bph.17358

PLoS One. 2024 Oct 10;19(10):e0311267. doi: 10.1371/journal.pone.0311267. eCollection 2024.

ABSTRACT

BACKGROUND: Pharmacogenetic testing in routine care could provide benefits for patients, doctors and statutory health insurances. Therefore, the aim of the retrospective, observational study Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung (EMPAR) was to analyze the relationship between pharmacogenetic profiles, the risk of adverse drug reactions, and patients' perceptions of drug therapy in 10748 adult (≥18 years) participants in Germany.

METHODS: A questionnaire was used to assess views and beliefs about medicines and participants individual perception of sensitivity to drug therapies. The questionnaire consisted of the Beliefs about Medicines Questionnaire (BMQ)-General scales (Overuse, Harm, Benefit), the Perceived Sensitivity to Medicines (PSM), Natural Remedy, and Gene Testing scales. The influence of gender, age, study collective, genotype and phenotype of relevant pharmacogenes on participant's perception were evaluated.

RESULTS: Overuse, PSM and Benefit scores were significantly higher among patients of the collective International Classification of Diseases and Health Related Disorders (ICD)-10 Y57.9! diagnosis, which indicates complications related to drugs, compared to the anticoagulant/antiplatelet and cholesterol-lowering drug collective. Age and gender also played a significant role in patients' perceptions, with younger patients and female participants more likely to believe in medication overuse according to the Overuse scale score compared to older and male participants. Female participants compared to male participants and the old age group compared to the young and/or middle-age subgroup, scored higher in PSM and/or Harm scales, respectively. Only a tendency of increased Harm, Overuse and PSM scores was observed in the participant group with five or more relevant actionable variants compared to subgroups with 0 up to 4 variants.

CONCLUSIONS: In conclusion, patients' beliefs about medicines and their drug sensitivity perceptions are influenced by various factors including age, gender, previous complications with medicines, and with some tendency also pharmacogenetic profiles. The higher association with more negative views related to treatment indicates that there is a need to target the underlying issues in affected patient groups in order to improve compliance to treatment and outcomes in routine care. Trial registration: EMPAR was registered in the German Clinical Trials Register (DRKS) on 06 July 2018 (DRKS00013909).

PMID:39388460 | PMC:PMC11466409 | DOI:10.1371/journal.pone.0311267

Hong Kong Med J. 2024 Oct 10. doi: 10.12809/hkmj2311194. Online ahead of print.

ABSTRACT

INTRODUCTION: Paracetamol is generally safe at normal therapeutic doses of ≤4 g/day in adults. However, paracetamol-induced hepatotoxicity after normal therapeutic doses use has been reported. We investigated the epidemiology of this adverse drug reaction in the Hong Kong Chinese population.

METHODS: This territory-wide retrospective observational study included adult patients with suspected paracetamol-induced hepatotoxicity after normal therapeutic doses use from January 2011 to June 2022. We evaluated the demographic characteristics; paracetamol dose, duration, and reason for use; preexisting hepatotoxicity risk factors; laboratory findings; and their relationship with clinical outcomes.

RESULTS: We identified 76 patients (median age: 74 years, 23 males) with suspected paracetamolinduced hepatotoxicity after normal therapeutic doses use. There were 14 cases with significant clinical outcomes (five deaths and nine cases of acute hepatic failure), with an incidence of 1.2 cases per year. For patients with significant clinical outcomes, they were significantly older (age >80 years), had a lower body weight (<50 kg), exposed to longer durations (>2 days) and higher daily doses (>3 g), and with higher proportion of malnutrition.

CONCLUSION: Paracetamol-induced hepatotoxicity can occur at normal therapeutic doses in the Hong Kong Chinese population. The identified risk factors are consistent with international guidelines regarding susceptible patients. Considering the widespread local use of paracetamol and low incidence of severe hepatotoxicity, the current dosage recommendations are considered safe for the general population. For susceptible patients, a reduced maximum dose of ≤3 g/day is recommended, with liver function and serum paracetamol monitoring in place.

PMID:39385704 | DOI:10.12809/hkmj2311194

Bioinformatics. 2024 Oct 1;40(10):btae596. doi: 10.1093/bioinformatics/btae596.

ABSTRACT

MOTIVATION: Drug-drug interactions (DDIs) can cause unexpected adverse drug reactions, affecting treatment efficacy and patient safety. The need for computational methods to predict DDIs has been growing due to the necessity of identifying potential risks associated with drug combinations in advance. Although several deep learning methods have been recently proposed to predict DDIs, many overlook feature learning based on interactions between the substructures of drug pairs.

RESULTS: In this work, we introduce a molecular Substructure-based Dual Attention Feature Learning framework (MSDAFL), designed to fully utilize the information between substructures of drug pairs to enhance the performance of DDI prediction. We employ a self-attention module to obtain a set number of self-attention vectors, which are associated with various substructural patterns of the drug molecule itself, while also extracting interaction vectors representing inter-substructure interactions between drugs through an interactive attention module. Subsequently, an interaction module based on cosine similarity is used to further capture the interactive characteristics between the self-attention vectors of drug pairs. We also perform normalization after the interaction feature extraction to mitigate overfitting. After applying three-fold cross-validation, the MSDAFL model achieved average precision scores of 0.9707, 0.9991, and 0.9987, and area under the receiver operating characteristic curve scores of 0.9874, 0.9934, and 0.9974 on three datasets, respectively. In addition, the experiment results of five-fold cross-validation and cross-datum study also indicate that MSDAFL performs well in predicting DDIs.

AVAILABILITY AND IMPLEMENTATION: Data and source codes are available at https://github.com/27167199/MSDAFL.

PMID:39383521 | DOI:10.1093/bioinformatics/btae596

Sci Rep. 2024 Oct 9;14(1):23534. doi: 10.1038/s41598-024-74623-x.

ABSTRACT

Immunoglobulin E (IgE)-mediated immediate hypersensitivity reactions are the most concerning adverse events after penicillin antibiotics (PENs) administration because of their rapid progression and potential for fatal outcome. However, the diagnosis of allergic death is a forensic challenge because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. In this study, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was used to screen potential forensic biomarkers of fatal anaphylactic shock induced by four PENs (benzylpenicillin (BP), amoxicillin (AMX), oxacillin (OXA), and mezlocillin (MEZ)), and analyzed the metabolites, metabolic pathway and the mechanism which were closely related to the allergic reactions. The metabolomics results discovered that a total of 24 different metabolites in all four anaphylactic death (AD) groups, seven of which were common metabolites. A biomarker model consisting of six common metabolites (linoleic acid, prostaglandin D2, lysophosphatidylcholine (18:0), N-acetylhistamine, citric acid and indolelactic acid) AUC value of Receiver Operating Characteristic (ROC) curve was 0.978. Metabolism pathway analysis revealed that the pathogenesis of PENs-induced AD is closely related to linoleic acid metabolism. Our results revealed that the metabolomic profiling has potential in PENs-induced AD post-mortem diagnosis and metabolic mechanism investigations.

PMID:39384950 | PMC:PMC11464644 | DOI:10.1038/s41598-024-74623-x

Sci Rep. 2024 Oct 9;14(1):23636. doi: 10.1038/s41598-024-74505-2.

ABSTRACT

The presence of adverse drug reactions (ADRs) is an ongoing public health concern. While traditional methods to discover ADRs are very costly and limited, it is prudent to predict ADRs through non-invasive methods such as machine learning based on existing data. Although various studies exist regarding ADR prediction using non-clinical data, a process that leverages both demographic and non-clinical data for ADR prediction is missing. In addition, the importance of individual features in ADR prediction has yet to be fully explored. This study aims to develop an ADR prediction model based on demographic and non-clinical data, where we identify the highest contributing factors. We focus our efforts on 30 common and severe ADRs reported to the Food and Drug Administration (FDA) between 2012 and 2023. We have developed a random forest (RF) and deep learning (DL) machine learning model that ingests demographic data (e.g., Age and Gender of patients) and non-clinical data, which includes chemical, molecular, and biological drug characteristics. We successfully unified both demographic and non-clinical data sources within a complete dataset regarding ADR prediction. Model performances were assessed via the area under the receiver operating characteristic curve (AUC) and the mean average precision (MAP). We demonstrated that our parsimonious models, which include only the top 20 most important features comprising 5 demographic features and 15 non-clinical features (13 molecular and 2 biological), achieve ADR prediction performance comparable to a less practical, feature-rich model consisting of all 2,315 features. Specifically, our models achieved an AUC of 0.611 and 0.674 for RF and DL algorithms, respectively. We hope our research provides researchers and clinicians with valuable insights and facilitates future research designs by identifying top ADR predictors (including demographic information) and practical parsimonious models.

PMID:39384938 | PMC:PMC11464664 | DOI:10.1038/s41598-024-74505-2

Sci Rep. 2024 Oct 9;14(1):23624. doi: 10.1038/s41598-024-74744-3.

ABSTRACT

Congenital anomalies of the external ear can have a significant impact on a child's development and quality of life. While genetic factors play a crucial role in the etiology of these anomalies, environmental factors such as drug exposure during pregnancy may also contribute to their occurrence. This study aims to investigate the association between drug exposure and congenital anomalies of the external ear using data from an adverse drug reaction report database. Using OpenVigil 2.1, we queried the FAERS database to retrieve adverse event reports from the first quarter of 2004 to the first quarter of 2024. To identify relevant cases, we used Medical Dictionary for Regulatory Activities terms focusing on congenital anomalies of the external ear. Drug generic names were sourced from the DrugBank database. To assess safety signals and rank drugs by their signal strength, we conducted a disproportionality analysis, generating reporting odds ratios (ROR) and proportional reporting ratios (PRR). A total of 20,754,281 AE reports were identified in the FAERS database from Q1 2004 to Q1 2024, of which 1763 were related to congenital anomalies of the external ear. Valproic acid (122 cases) was associated with the most cases, followed by mycophenolate mofetil (105 cases) and lamotrigine (65 cases). According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were primidone (ROR: 397.05, 95% CI 147.21, 1070.9; PRR: 388.71, 95% CI 145.89, 1035.7), valproic acid (ROR: 239.46, 95% CI 123.75, 463.37; PRR: 236.42, 95% CI 123.82, 451.43), tapazole (ROR: 198.35, 95% CI 63.49, 619.67; PRR: 196.25, 95% CI 62.97, 611.67), nevirapine (ROR: 138.24, 95% CI 82.9, 230.51; PRR: 137.23, 95% CI 82.44, 228.44), and sebivo (ROR: 117.1, 95% CI 48.51, 282.67; PRR: 116.37, 95% CI 48.17, 281.12). This study identified several drugs significantly associated with congenital anomalies of the external ear in the FAERS database using disproportionality analysis. The findings can help healthcare professionals better recognize and manage drug-induced congenital anomalies of the external ear, particularly when prescribing high-risk medications. Further research is needed to elucidate the mechanisms underlying these associations and develop strategies for preventing and mitigating drug-induced congenital anomalies of the external ear.

PMID:39384812 | PMC:PMC11464839 | DOI:10.1038/s41598-024-74744-3

Kidney Res Clin Pract. 2024 Sep 11. doi: 10.23876/j.krcp.24.067. Online ahead of print.

ABSTRACT

BACKGROUND: Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by the Korean Ministry of Food and Drug Safety in 2015 as a treatment option for autosomal dominant polycystic kidney disease (ADPKD). To prescribe tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease stages 1 to 3.

METHODS: A total of 117 Korean patients aged 19 to 50 years with rapidly progressing ADPKD were enrolled in the study. Tolvaptan was prescribed for 24 months with the maximum tolerable dose up to 120 mg/day. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs) including hepatic adverse events. The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR).

RESULTS: A total of 489 TEAEs occurred in 106 patients (90.6%). A total of 17 cases of hepatic adverse events (14.5%) occurred during the study period and mostly within the first 18-month period. However, liver enzymes were normalized after drug discontinuation. Although it was not statistically significant, patients with a previous history of liver disease as well as those with mild elevation of liver enzyme showed a higher frequency of hepatic adverse events. Compared with the predicted value from the calculation, tolvaptan attenuated both TKV growth and eGFR decline rate.

CONCLUSION: Although the incidence of hepatic adverse events was higher in Korean ADPKD patients compared to the previous studies, tolvaptan can be prescribed safely and effectively using meticulous titration and 1-month interval monitoring.

PMID:39384353 | DOI:10.23876/j.krcp.24.067

Am J Gastroenterol. 2024 Oct 9. doi: 10.14309/ajg.0000000000003119. Online ahead of print.

ABSTRACT

Drug-induced acne is a common side effect to a wide array of pharmacological therapies and is characterized by a monomorphic, papulopustular eruption typically affecting the face, scalp, and the upper thorax. Corticosteroids and Janus kinase inhibitors (JAKi) are commonly used for the treatment of inflammatory bowel disease (IBD) and are known to aggravate a prior tendency to acne or trigger the development of new acneiform eruptions. Recent attention on managing drug-induced acne has been driven by the increasing use of JAKi, an expanding therapeutic class in IBD and several other immune-mediated inflammatory diseases. Both randomized controlled trials and real-world studies have identified acne as one of the most common treatment-emergent adverse events in JAKi. Left untreated, this common skin reaction can significantly impact patient self-esteem and quality of life leading to poor treatment adherence and suboptimal IBD control. This review examines the characteristics of drug-induced acne in IBD treatments, provides a practical guide for gastroenterologists to manage mild to moderate occurrences, and highlights when to seek specialist dermatology advice. Such approaches enable early treatment of a common and often distressing adverse event and optimizes the management of IBD by preventing the premature discontinuation or dose reduction of efficacious IBD drugs.

PMID:39382676 | DOI:10.14309/ajg.0000000000003119

Indian J Med Res. 2024 May;159(5):410-420. doi: 10.25259/ijmr_945_23.

ABSTRACT

Background & objectives Medication-related harm is known to be the cause for about 1/10th of hospitalizations. Some estimates from India show that about 90 per cent of medicines consumed are inessential or irrational and contribute towards high out-of-pocket expenditure on health. In this context, the Indian Council of Medical Research in 2022 constituted a National Task Force (NTF) to explore possible solutions that could improve safe and rational use of medicines (SRUMs). The objective of this study was to identify research ideas in the field of SRUM through a survey of relevant stakeholders, and further to prioritize the research ideas using a pre-identified set of criteria. Methods The responses from the identified stakeholders were assessed using the Child Health and Nutrition Research Initiative method, which is an established research priority-setting methodology. First, the NTF asked for two to six research ideas from relevant Indian and global stakeholders on solutions to improve SRUM. The ideas were checked for duplicates, re-phrased where necessary and classified into various sub-themes. Subsequently, the research ideas were scored by Indian experts with relevant technical expertise using a pre-defined set of five criteria: innovativeness, effectiveness, translational value, answerability and applicability. Each research idea received from a stakeholder was assigned a score under each of the five criteria. The overall research priority score was calculated as a mean of all five criteria-specific scores and converted into a percentage. Results The final output of the prioritization process was a list of research ideas or questions, ranked by their scores. Total 209 unique ideas were received from 190 respondents, which were scored by 27 experts. The top three research topics on medication safety focused on cost-effective strategies for improving antimicrobial stewardship, safe use of poly-pharmacy in geriatric patients and drug take-back policy interventions. Regarding the rational use of medicine, the top three topics included testing mobile application-based antimicrobial stewardship interventions, development of diagnostics for antimicrobial resistance, and behavioural interventions. Interpretation & conclusions Several priority ideas found in this study also align with those of global priority, e.g., safe disposal practices and enhanced pharmacovigilance, rational use of medicines. Patient engagement, which underlines many of the top scoring ideas found in this study, is also inclined with the top research priorities reported by the WHO priority exercise on research into the safe use of medicines. However, to the best of our knowledge, this is the first such work from a low- and middle- income country on medication safety and rational use of medicines. The findings of this research priority-setting exercise can help to guide research for the development of policy-relevant and novel interventions to improve SRUM in India.

PMID:39382419 | PMC:PMC11463240 | DOI:10.25259/ijmr_945_23

J Tradit Chin Med. 2024 Oct;44(5):1000-1005. doi: 10.19852/j.cnki.jtcm.20240806.008.

ABSTRACT

OBJECTIVE: To assess clinical value of modified Shenling Baizhu powder (, SBP) in intervening targeted therapy-induced diarrhea.

METHODS: This study was a prospective randomized controlled study. Eighty-five non-small cell lung cancer (NSCLC) patients with diarrhea who took targeted drugs were randomly divided into two groups. The experimental group received modified SBP, while the control group received imodium. During 2 courses of treatment (1 week/course) and 2 weeks of follow-up, we observed remission and recurrence of diarrhea, as well as the improvement of Karnofsky score (KPS) in the two groups and drug safety.

RESULTS: Eighty cases were completed, with 40 cases in the experimental group and 40 cases in the control group. The control group's diarrhea remission rate was significantly lower than the experimental group's (P<0.05). After 2 courses of treatment, the symptom scores of both groups were lower than before, with that of the experimental group remarkably lower (P<0.05). Furthermore, the experimental group experienced less abdominal fullness and appetite loss than the control group (P<0.05). There was no prominent difference in overall diarrhea recurrence, time, or KPS after treatment between the two groups (P>0.05). No unique adverse events occurred in experimental group or control group.

CONCLUSION: The modified SBP could improve targeted therapy-induced diarrhea in NSCLC, and is superior to imodium in relieving diarrhea, improving related symptom scores and symptoms, with no obvious drug-related adverse events.

PMID:39380231 | PMC:PMC11462525 | DOI:10.19852/j.cnki.jtcm.20240806.008

BMC Pulm Med. 2024 Oct 8;24(1):495. doi: 10.1186/s12890-024-03284-3.

ABSTRACT

BACKGROUND: Immune-related pneumonitis (irP) is one of the most important immune-related adverse events caused by immune checkpoint inhibitors (ICIs). After corticosteroid therapy irP frequently relapses, which can interfere with cancer therapy. However, risk factors for irP relapse are unknown.

METHODS: This study was a follow-up analysis of a phase II study that evaluated 56 patients with grade ≥ 2 irP treated with oral prednisolone, 1 mg/kg/day, tapered over 6 weeks. Clinical factors including patient characteristics, blood test findings, and response to prednisolone therapy were assessed to identify risk factors for irP relapse using the Fine-Gray test.

RESULTS: Among 56 patients with irP, 22 (39.3%) experienced irP relapse after 6 weeks of prednisolone therapy during the follow-up observation period. Radiographic organising pneumonia (OP) pattern and duration to irP onset ≥ 100 days from ICI initiation were determined to be significant risk factors for irP relapse in a multivariate Fine-Gray test (hazard ratio [HR] = 3.17, 95% CI 1.37-7.32, p = 0.007, and HR = 2.61, 95% CI 1.01-6.74, p = 0.048, respectively). Other patient characteristics, blood test findings, irP severity, and response to prednisolone therapy were not associated with irP relapse.

CONCLUSIONS: In irP patients treated with 6-week prednisolone tapering therapy, OP pattern and duration to irP onset ≥ 100 days were associated with relapse risk. Assessment of the risk factors for irP relapse will be helpful for irP management.

PMID:39379903 | PMC:PMC11462669 | DOI:10.1186/s12890-024-03284-3

BMC Bioinformatics. 2024 Oct 8;25(1):324. doi: 10.1186/s12859-024-05915-2.

ABSTRACT

BACKGROUND: Safe drug treatment requires an understanding of the potential side effects. Identifying the frequency of drug side effects can reduce the risks associated with drug use. However, existing computational methods for predicting drug side effect frequencies heavily depend on known drug side effect frequency information. Consequently, these methods face challenges when predicting the side effect frequencies of new drugs. Although a few methods can predict the side effect frequencies of new drugs, they exhibit unreliable performance owing to the exclusion of drug-side effect relationships.

RESULTS: This study proposed CrossFeat, a model based on convolutional neural network-transformer architecture with cross-feature learning that can predict the occurrence and frequency of drug side effects for new drugs, even in the absence of information regarding drug-side effect relationships. CrossFeat facilitates the concurrent learning of drugs and side effect information within its transformer architecture. This simultaneous exchange of information enables drugs to learn about their associated side effects, while side effects concurrently acquire information about the respective drugs. Such bidirectional learning allows for the comprehensive integration of drug and side effect knowledge. Our five-fold cross-validation experiments demonstrated that CrossFeat outperforms existing studies in predicting side effect frequencies for new drugs without prior knowledge.

CONCLUSIONS: Our model offers a promising approach for predicting the drug side effect frequencies, particularly for new drugs where prior information is limited. CrossFeat's superior performance in cross-validation experiments, along with evidence from case studies and ablation experiments, highlights its effectiveness.

PMID:39379821 | PMC:PMC11459996 | DOI:10.1186/s12859-024-05915-2

Hum Vaccin Immunother. 2024 Dec 31;20(1):2410557. doi: 10.1080/21645515.2024.2410557. Epub 2024 Oct 8.

ABSTRACT

This study utilized meta-analysis and Mendelian randomization (MR) to identify risk factors for endocrine-related immune-related adverse events (EirAEs) and to ascertain whether EirAEs confer better prognosis of immunotherapy. The meta-analysis identified several risk factors for EirAEs, including elevated baseline TSH (OR = 1.30, 95% CI 1.10-1.53), positive TgAb (OR = 14.23, p < .001), positive TPOAb (OR = 3.75, p < .001), prior thyroid-related medical history (OR = 4.19), increased BMI (OR = 1.11), combination immune checkpoint inhibitors (ICIs) therapy with targeted treatment (OR = 2.71, 95% CI 2.11-3.47), and dual ICI therapy (OR = 3.26, 95% CI 2.22-4.79). MR analysis further supported causalities between extreme BMI, hypothyroidism, and irAEs from a genetic perspective. In addition, cancer patients who experienced EirAEs exhibited significantly prolonged PFS (HR = 0.84, 95% CI 0.73-0.97) and OS (HR = 0.59, 95% CI 0.45-0.76) compared to those without. These findings provide valuable insights for clinical decision-making among healthcare professionals and offer direction for future research in this field.

PMID:39377304 | PMC:PMC11469449 | DOI:10.1080/21645515.2024.2410557

Hum Vaccin Immunother. 2024 Dec 31;20(1):2406060. doi: 10.1080/21645515.2024.2406060. Epub 2024 Oct 8.

ABSTRACT

In South Korea, a combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) is available since 2018 for vaccination of infants from the age of 2 months. This prospective, observational, non-comparative, post-marketing study evaluated the real-world safety of DTaP-IPV/Hib primary vaccination in eligible South Korean infants from the age of 2 months between 2018 and 2022. Infants were followed up for 30 days after each vaccine dose to assess the proportion of infants experiencing any adverse event (AE), including adverse drug reactions (ADRs), unexpected AEs, and serious AEs/serious ADRs (SAEs/SADRs). Of 660 infants vaccinated during the study period, 646 were included in the total safety cohort. A total of 194 AEs were reported in 143 (22.1%) infants; 158 AEs occurred after the first dose in 130 (20.1%) infants, 21 after the second dose in 20 (13.4%) infants, and 11 after the third dose in ten (8.1%) infants. The most frequent AEs by Medical Dictionary for Regulatory Activities Preferred Terms terminology were pyrexia (13.3%), injection site swelling (5.1%), and irritability (1.7%). Most of the AEs were mild, resolved without a medical visit, and were classified as possibly related to vaccination. The incidence proportions of ADRs, unexpected AEs, and SAEs/SADRs were 19.4%, 4.3%, and 0.9%, respectively. All SAEs/SADRs resolved after hospitalization or emergency room visit, and one event was possibly related to vaccination. These results are in line with the approved label and other national/international studies, confirming the acceptable safety profile of DTaP-IPV/Hib in the South Korean pediatric population.

PMID:39376187 | PMC:PMC11469445 | DOI:10.1080/21645515.2024.2406060