BMJ Open. 2025 Jun 23;15(6):e094409. doi: 10.1136/bmjopen-2024-094409.

ABSTRACT

OBJECTIVE: Amoxicillin-clavulanate is commonly used to prevent infections following snakebites despite the lack of clinical evidence. We aimed to demonstrate that clinically directed initiation of amoxicillin-clavulanate would be non-inferior to routine use in this setting.

DESIGN: Open-label, randomised, non-inferiority trial with blinded adjudication of endpoints.

SETTING: Emergency department of a teaching hospital in southern India.

PARTICIPANTS: Adults with local swelling following snakebites within 24 hours of bite.

INTERVENTIONS: In the routine use strategy, intravenous followed by oral amoxicillin-clavulanate was administered for at least 5 days. In the clinically directed strategy, the antibiotic was only initiated for clinical failures.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were protocol-defined clinical failure and total antibiotic consumption. Non-inferiority margin was prespecified as 10%. Secondary outcomes were the length of hospital stay, total antivenom consumption, new-onset organ failure, bleeding requiring transfusion, death/need for surgical intervention and drug-related adverse events.

RESULTS: The trial was prematurely stopped due to the COVID-19 situation after randomising 66 patients-34 to clinically directed initiation and 32 to routine use arms. Russell's viper was the most common (21 (32%)) biting snake species identified; 52 (79%) patients had evidence of haemotoxic envenomation at baseline, and 24 (36%) patients developed AKI. There were 10 clinical failures-six in the clinically directed initiation arm and four in the routine use arm. The difference in clinical failure between the two arms was 5.2% (-12.0%-21.7%; p=0.291); the upper bound of the CI exceeded the prespecified non-inferiority margin. Total antibiotic consumption, expressed in DDDs, was significantly lower in the clinically directed initiation arm (0 (0-1) vs 5.31 (4.67-6.17); p<0.001). Three serious adverse events resulting in two deaths (one in each arm) were observed.

CONCLUSIONS: We could not demonstrate the non-inferiority of clinically directed initiation compared with routine use of amoxicillin-clavulanate among patients with local swelling caused by haemotoxic snakebites. However, the frequency of clinical failures was similar, and antibiotic consumption was substantially lower with the clinically directed initiation strategy.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov; NCT02570347.

PMID:40550712 | DOI:10.1136/bmjopen-2024-094409

Adv Ther. 2025 Jun 23. doi: 10.1007/s12325-025-03253-0. Online ahead of print.

ABSTRACT

INTRODUCTION: This trial evaluated long-term safety, tolerability, and maintenance of efficacy of adjunctive brivaracetam (BRV) in Japanese and Chinese patients aged ≥ 16 years with focal-onset seizures (FOS).

METHODS: Interim analysis of data from EP0085 (NCT03250377), a long-term follow-up trial of adjunctive BRV 50-200 mg/day in Japanese and Chinese patients. Post hoc analyses assessed efficacy for 12- and 24-month completers and BRV retention.

RESULTS: At data cutoff (June 1, 2023), 207 patients had enrolled; of these, 157 (75.8%) were ongoing and 50 (24.2%) had discontinued. Overall, 137 patients were 12-month completers and 63 were 24-month completers. Mean age was 36.7 years and 107 (51.7%) patients were female (100 [48.3%] male). Mean duration of epilepsy was 17.16 years. At data cutoff, total duration of BRV exposure was 378.5 patient-years. Mean duration of BRV exposure was 667.8 days (median 427.0 days), with a median modal dose of 200.0 mg/day (range 25.0-200.0 mg/day). Kaplan-Meier-estimated BRV retention rates at 12, 24, and 36 months were 85%, 76%, and 68%, respectively. Treatment-emergent adverse events (TEAEs) were reported by 184 (88.9%) patients, drug-related TEAEs by 60 (29.0%), serious TEAEs by 29 (14.0%), and 8 (3.9%) discontinued as a result of TEAEs. Median FOS frequency/28 days decreased from 7.59 during baseline to 4.11 during the evaluation period. For the overall evaluation period, 12-month, and 24-month completers, median percentage reductions from baseline in FOS frequency/28 days were 42.4%, 44.0%, and 38.9%, respectively, and 50% responder rates were 46.4%, 46.7%, and 38.1%.

CONCLUSION: Based on this interim and post hoc analysis, long-term adjunctive BRV was well tolerated and efficacious in Japanese and Chinese patients with FOS. The efficacy response was maintained over time in those completing 12 and 24 months of trial participation. Overall, 68% of patients remained on BRV treatment for 3 years.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03250377. Graphical abstract available for this article.

PMID:40549270 | DOI:10.1007/s12325-025-03253-0

Z Kinder Jugendpsychiatr Psychother. 2025 Jun 23. doi: 10.1024/1422-4917/a001034. Online ahead of print.

ABSTRACT

Objective: Attention-deficit/hyperactivity disorder (ADHD) affects 6-10 % of children and adolescents worldwide. While psychopharmacological treatments effectively reduce symptoms, incomplete adherence is common, diminishing their effectiveness. This study investigated medication nonadherence and its predictors in children and adolescents with ADHD. Method: The TDM-VIGIL study, a multicenter prospective observational study in Germany, examined drug-related risks of ADHD medication in hyperkinetic disorders and nonadherence. Participants aged 6-18 years with ADHD (ICD-10/DSM-IV) starting stimulants or nonstimulants were assessed for nonadherence using the Medication Assessment Questionnaire (MAQ) at multiple time points. Patients were classified as fully or not fully adherent, and logistic regression analysis was used to identify predictors. Results: Among 198 participants (mean age = 10.4 years), 66.1 %-75.4 % were fully adherent across time points. Higher age and lower intelligence were significantly associated with nonadherence, while sex, disease severity, adverse events, treatment setting (outpatient, day clinic, inpatient), medication class (stimulant, nonstimulant), and treatment strategy (mono- versus polypharmacy) were not. Conclusions: Medication nonadherence is common in youth with ADHD, with higher age and lower intelligence representing relevant risk factors. Clinicians should consistently monitor adherence and address individual barriers.

PMID:40548886 | DOI:10.1024/1422-4917/a001034

Comput Struct Biotechnol J. 2025 May 26;27:2473-2480. doi: 10.1016/j.csbj.2025.05.029. eCollection 2025.

ABSTRACT

Multidrug combination therapy has long been a vital approach for treating complex diseases by leveraging synergistic effects between drugs. However, drug-drug interactions (DDIs) are not uniformly beneficial. Accurate and rapid identification of DDIs is critical to mitigate drug-related side effects. Currently, many computational-based methods have been used to expedite the prediction of DDIs. However, most of these methods use a single perspective to obtain drug features, which have limited expressive capabilities and cannot fully represent the essential attributes of drugs. In this study, we propose the Multi-view Feature Embedding for drug-drug interaction prediction (MFE-DDI), which integrates SMILES information, molecular graph data and atom spatial semantic information to model drugs from multiple perspectives and encapsulate the intricate drug information crucial for predicting DDIs. Concurrently, the feature information extracted from different feature encoding channels is fused in the attention-based fusion module to fully convey the essence of drugs. Consequently, this approach enhances the efficacy of the DDI prediction task. Experimental results indicate that MFE-DDI surpasses other baseline methods on three datasets. Moreover, analysis experiments demonstrate the robustness of the model and the necessity of each component of the model. Case studies on newly approved drugs demonstrate the effectiveness of our method in real scenarios. The code and data used in MFE-DDI can be found at https://github.com/2019040445/MFE_DDI.

PMID:40547454 | PMC:PMC12181007 | DOI:10.1016/j.csbj.2025.05.029

Cureus. 2025 May 23;17(5):e84690. doi: 10.7759/cureus.84690. eCollection 2025 May.

ABSTRACT

A 21-year-old Asian man developed asymmetrical keratoconus (OD > OS) in the context of right-sided periocular vitiligo. The patient was undergoing topical pimecrolimus treatment for his vitiligo, which caused periocular eye irritation, leading to aggressive, unilateral right-eye rubbing. Subsequently, he developed ocular symptoms such as eye strain-related headaches, aggravated by screen use. There was no relevant past medical history or family history of ocular disease. Corneal topography and keratography confirmed the diagnosis of keratoconus. The patient underwent femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK) in the right eye and corneal cross-linking in the left eye to prevent progression. This case highlights a previously unreported association between periocular vitiligo, pimecrolimus-induced irritation, and subsequent keratoconus. The pathophysiological mechanism is likely multifactorial, involving mechanical stress from chronic eye rubbing and potential alterations in corneal biomechanics due to inflammatory mediators. Given the high prevalence of keratoconus among young patients and the increasing use of topical immunomodulators, this case underscores the need for heightened clinical awareness regarding periocular drug-induced irritation as a modifiable risk factor. It reinforces the importance of patient education on the risks associated with habitual eye rubbing and the need for cautious prescribing of periocular irritants, particularly in individuals at risk for corneal ectatic disorders. To our knowledge, this is the first case report demonstrating that periocular creams with known ocular irritation side effects can exacerbate eye rubbing, which may contribute to the onset and progression of keratoconus. Further research is warranted to explore preventive strategies and alternative therapeutic approaches to mitigate ocular irritation and keratoconus progression.

PMID:40546526 | PMC:PMC12182903 | DOI:10.7759/cureus.84690

Rev Iberoam Micol. 2025 Apr 4:S1130-1406(25)00019-1. doi: 10.1016/j.riam.2025.02.004. Online ahead of print.

ABSTRACT

Solid organ transplant (SOT) recipients have a higher risk of developing invasive fungal infection (IFI). Isavuconazole is a novel broad-spectrum azole active against Aspergillus and Mucor. Isavuconazole is well tolerated, shows an excellent bioavailability and predictable pharmacokinetics, good diffusion to tissues, significantly reduced drug-drug interactions with immunosuppressive drugs in comparison with other broad-spectrum azoles, and few serious adverse effects, including hepatic toxicity. We have performed an extensive literature review concerning the clinical experience on the use of isavuconazole in SOT as prophylaxis and treatment of IFI, which included the SOTIS and the ISASOT studies, and fourteen published case reports. Clinical response, all-cause and invasive aspergillosis-attributable mortality in recipients treated with isavuconazole were similar to those described with voriconazole. Drug-drug interactions with immunosuppressive agents were manageable after the adjustment of tacrolimus and mTOR inhibitors. Isavuconazole showed fewer drug-related side effects and a smaller rate of premature discontinuation than voriconazole. In conclusion, isavuconazole appears to be a reasonable option for the treatment of IFI in SOT, and can be an alternative to voriconazole as antifungal prophylaxis in lung transplantation. Nonetheless, more clinical studies are needed.

PMID:40545388 | DOI:10.1016/j.riam.2025.02.004

J Orthop Sci. 2025 Jun 20:S0949-2658(25)00176-9. doi: 10.1016/j.jos.2025.05.007. Online ahead of print.

ABSTRACT

BACKGROUND: To manage bone and soft tissue infection, continuous local antibiotics perfusion (CLAP) therapy, in which gentamicin is injected directly into the site of infection to control the infection, has been developed. However, gentamicin is nephrotoxic, and CLAP is often associated with complications, including acute kidney injury. Thus, in this study, we aimed to investigate the frequency of complications and the factors influencing their occurrence.

METHODS: Overall, 82 patients who underwent CLAP in our hospital between January 2020 and September 2023 were included in this study. We defined the occurrence of renal dysfunction within 1 month after CLAP as the primary outcome and evaluated the following factors: history of diabetes and liver dysfunction, site of injury, initial open wound, skin defect, hemodynamic compromise, concomitant antibiotics, type of treated tissue, purpose of treatment, drainage method, duration of CLAP, and total amount of the gentamicin dose. To identify prognostic factors, we performed a logistic regression analysis.

RESULTS: The mean follow-up was 10.3 months. Of the 82 patients, 50 were cured, 12 reached infection prevention, 14 had recurrent infection, three had their affected limb amputated, two did not achieve infection prevention, and one died. Side effects of treatment included decreased renal function in 13 cases and drug eruption in 1 case. Logistic regression analysis showed that age (Odds ratio: 1.07; 95 % Confidence interval [CI]: 1.01-1.13) and duration of CLAP (Odds ratio: 1.06; 95 % CI: 1.01-1.12) were significant prognostic factors for the occurrence of renal function decline.

CONCLUSIONS: This study shows that renal function deterioration due to gentamicin used during CLAP is relatively common. Consideration should be given to shortening the duration of CLAP in older adult patients. Considering pharmacokinetics, a variable concentration regimen of gentamicin may be more effective and less nephrotoxic than continuous administration of a fixed concentration.

PMID:40544111 | DOI:10.1016/j.jos.2025.05.007

Headache. 2025 Jun 20. doi: 10.1111/head.14995. Online ahead of print.

ABSTRACT

OBJECTIVES/BACKGROUND: This study was undertaken to compare the efficacy of the oral calcitonin gene-related peptide receptor antagonist rimegepant relative to placebo as a preventive treatment for migraine in Japan. This was the first randomized placebo-controlled trial of rimegepant for the preventive treatment of migraine to be conducted outside the United States and the second conducted globally.

METHODS: In this phase 3, double-blind, randomized, multicenter trial, conducted August 9, 2022 through January 18, 2024, adults in Japan with a history of 4-18 migraine attacks/month of moderate or severe pain intensity completed a 28-day observation phase and then took rimegepant 75 mg or placebo every other day during the 12-week double-blind treatment phase. The primary endpoint was the mean change from the observation phase in the number of monthly migraine days in the last 4 weeks of the double-blind treatment phase. Safety was assessed based on the frequency of adverse events and laboratory test abnormalities during the double-blind treatment phase.

RESULTS: A total of 484 (efficacy) and 496 (safety) treated participants were evaluable. During the observation phase, participants in the rimegepant and placebo groups, respectively, reported a mean (SD) of 9.3 (3.1) and 9.0 (3.1) monthly migraine days. The study met its primary endpoint with a statistically significant difference in mean change from the observation phase in the number of monthly migraine days in the last 4 weeks of the double-blind treatment phase (difference rimegepant vs. placebo: -1.1 [95% confidence interval = -1.73 to -0.38], p = 0.002). In the rimegepant and placebo groups, respectively, 54.7% and 41.0% of participants reported adverse events and 0.8% and 0.4% reported serious adverse events during the double-blind treatment phase. No signal of drug-induced liver injury due to rimegepant was identified.

CONCLUSION: Rimegepant 75 mg every other day demonstrated efficacy superior to that of placebo for the preventive treatment of migraine, with a favorable safety profile. NCT05399485.

PLAIN LANGUAGE SUMMARY: This study tested the effectiveness of rimegepant for migraine prevention in Japan. Results showed that rimegepant was more effective than placebo in reducing monthly migraine days, with very few adverse effects. These results support the previous findings from a clinical study conducted in the United States and broaden them to a wider population.

PMID:40542538 | DOI:10.1111/head.14995

Pharmacogenomics. 2025 Apr-Apr;26(5-6):207-221. doi: 10.1080/14622416.2025.2509479. Epub 2025 Jun 20.

ABSTRACT

Tuberculosis is the leading cause of death from a single infectious agent globally, with the highest burden in low-and middle-income countries. Successful treatment requires prolonged administration of multiple drugs. The increasing threat of multidrug-resistant tuberculosis has prompted the development of a robust pipeline for new drugs. While generally safe and well tolerated, adverse drug reactions (ADRs) to TB drugs have a considerable impact on treatment outcomes. Pharmacogenetic testing has been implemented for some diseases to identify at-risk individuals and prevent ADRs. For tuberculosis treatment, the use of pharmacogenetic testing to optimize complex regimens and avoid ADRs is appealing, but there has been minimal implementation. To improve the use of pharmacogenetics, understanding both the pharmacology of relevant drugs and population-specific pathophysiology of ADRs are essential. This review highlights the major treatment-limiting ADRs with TB drugs, the current understanding of drug metabolic pathways, ADR pathophysiology, and known pharmacogenetic risk alleles. We highlight research gaps and barriers to meaningful clinical use and implementation of pharmacogenomic testing to prevent adverse reactions to TB drugs.

PMID:40538374 | DOI:10.1080/14622416.2025.2509479

Lancet Oncol. 2025 Jun 17:S1470-2045(25)00233-5. doi: 10.1016/S1470-2045(25)00233-5. Online ahead of print.

ABSTRACT

BACKGROUND: The addition of 10 mg olanzapine to the standard triplet antiemetic therapy has shown superiority in controlling chemotherapy-induced nausea and vomiting compared with triplet therapy alone for highly emetogenic chemotherapy, albeit with sedative side-effects. We aimed to investigate if administering 5 mg of olanzapine at home after anthracycline plus cyclophosphamide chemotherapy, rather than before chemotherapy, can maintain efficacy in controlling chemotherapy-induced nausea and vomiting while minimising sedative side-effects and associated risks.

METHODS: This was a phase 3, double-blind, randomised, placebo-controlled trial, done in 15 hospitals and cancer centres in Japan. Eligible patients were female adults aged 20 years or older with stage I-III breast cancer and an Eastern Cooperative Oncology Group performance status of 0-1, who were scheduled to receive intravenous anthracycline plus cyclophosphamide-based chemotherapy, and were naive to chemotherapy or had never received moderately to highly emetogenic chemotherapy. Eligible patients were randomly assigned 1:1 to oral olanzapine 5 mg or placebo via the central registration system. Randomisation was performed using blocked stratification, with age (≥55 years vs <55 years) and institution as stratification factors and a block size of two. Allocation was concealed and masking was achieved by using tablets with identical appearance. Treatment was administered at home within 5 h after the end of anthracycline plus cyclophosphamide administration and before the patient's evening meal on day 1 to minimise the risk of sedation during hospital visits and transportation, and on the next 3 days after their evening meal, both with pre-chemotherapeutical application of intravenous dexamethasone 9·9 mg, intravenous palonosetron 0·75 mg, and oral aprepitant 125 mg on day 1 followed by an additional dose of aprepitant 80 mg on days 2 and 3 or intravenous fosaprepitant 150 mg as a premedication on day 1. The primary endpoint was the proportion of patients with a complete response, defined as no vomiting and no rescue medication during the overall phase (0-120 h after the initiation of anthracycline plus cyclophosphamide) based on patient diary. The primary analysis was done by modified intention-to-treat, including all patients who received at least one dose of the study treatment and had at least one efficacy evaluation. Safety was analysed in all patients who received any treatment. This trial was registered with the Japan Registry of Clinical Trials, jRCT1031200134, and is complete.

FINDINGS: Between Oct 26, 2020 and Nov 2, 2022, 500 female patients from 15 medical institutions in Japan were randomly assigned to receive olanzapine (n=251) or placebo (n=249). Median age at enrolment was 52 years (IQR 45-60) in the olanzapine group and 51 years (46-60) in the placebo group. Data on gender and race or ethnicity were not collected. The median follow-up was 168 h (IQR 168-168). 480 participants (246 in the olanzapine group and 234 in the placebo group) received at least one dose of study medication and were eligible for the efficacy analysis. The complete response rate in the olanzapine group (58·1%, n=143) was significantly higher than in the placebo group (35·5%, n=83; difference 22·7%, 95% CI 14·0-31·4%; p<0·0001) during the overall phase. The most frequently reported severe or very severe symptoms based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) version 1.0 were anorexia (33 [13%] of 246 patients in the olanzapine group vs 89 [38%] of 235 in the placebo group) and constipation (30 [12%] vs 37 [16%]). Severe or very severe concentration impairment was reported in 25 (10%) of 246 patients in the olanzapine group and 34 (14%) of 235 patients in the placebo group. Experimental drug-related grade 3-4 adverse events according to the Common Terminology Criteria for Adverse Events version 5.0 included somnolence (four [2%] of 246 patients in the olanzapine group vs none of 235 in the placebo group), and concentration impairment (two [1%] vs none). There were no deaths.

INTERPRETATION: Post-chemotherapy administration of 5 mg olanzapine in combination with triplet antiemetic therapy before anthracycline plus cyclophosphamide-based chemotherapy significantly improved the complete response rate for chemotherapy-induced nausea and vomiting during the overall phase compared with placebo in female patients with breast cancer receiving outpatient chemotherapy, with an acceptable level of safety. The findings represent a substantial advancement in managing chemotherapy-induced nausea and vomiting and provide assurance that the safe and effective administration of olanzapine can be achieved at a dosage of 5 mg.

FUNDING: The Capture of Outstanding Clinical Research and Evolution (CORE) project at Juntendo University.

PMID:40541214 | DOI:10.1016/S1470-2045(25)00233-5

Drug Ther Bull. 2025 Jun 19:dtb-2024-000051. doi: 10.1136/dtb.2024.000051. Online ahead of print.

NO ABSTRACT

PMID:40537173 | DOI:10.1136/dtb.2024.000051

Adv Ther. 2025 Jun 19. doi: 10.1007/s12325-025-03255-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Receptor-interacting protein kinase 1 (RIPK1) is a master regulator of inflammation and necroptotic cell death and is implicated in the pathogenesis of several inflammatory and neurodegenerative diseases. This first-in-human study assessed the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of eclitasertib, a selective, peripherally-restricted, oral inhibitor of RIPK1.

METHODS: This 2-part Phase I trial enrolled healthy participants aged 18-55 years. Part 1 consisted of 2 sub-parts. Part 1a was a double-blind, randomized, single ascending dose (SAD) study with 6 cohorts of 8 participants each randomized 3:1 to single oral dose of eclitasertib (10 mg, 30 mg, 100 mg, 200 mg, 400 mg, or 800 mg) or placebo. Part 1b was an open-label, randomized, three-sequence, cross-over design study to evaluate the relative bioavailability of the prototype formulation versus the drug substance and the effect of food in an independent cohort of 10 participants. Part 2 was a double-blind, randomized, multiple ascending dose study (MAD) with 4 cohorts of 10 participants each randomized 4:1 to receive eclitasertib (50 mg, 100 mg, 200 mg, or 600 mg once daily) or placebo orally for 14 days. Incidence of adverse events (AEs; primary outcome), PK (secondary outcome), and PD properties (exploratory outcome; assessed by reduction in levels of S166 phosphorylated RIPK1) were evaluated.

RESULTS: Single and multiple oral doses of eclitasertib were well tolerated, with no study drug-related severe or serious AEs reported. Medical device-site reactions (includes AEs classified as device-site reaction, vessel puncture-site hematoma/pain, catheter-site pain/hematoma and catheter-site-related reactions) and headache were the most commonly reported AEs in both parts. Overall, the median Tmax ranged from 3 to 4 h. Cmax and AUC increased sub-dose proportionally. Administration of eclitasertib 100 mg following a high-fat meal did not significantly impact its bioavailability. At doses of 100 mg and above, > 90% inhibition of RIPK1 phosphorylation in human peripheral blood mononuclear cells was observed with eclitasertib at 12 h post-dose in both SAD and MAD studies.

CONCLUSIONS: Single and repeated doses of eclitasertib were well tolerated in healthy participants and potently inhibited RIPK1 activation.

TRIAL REGISTRATION: EudraCT 2019-001350-25.

PMID:40536759 | DOI:10.1007/s12325-025-03255-y

JID Innov. 2025 May 13;5(5):100381. doi: 10.1016/j.xjidi.2025.100381. eCollection 2025 Sep.

ABSTRACT

Although precision medicine is at least partially realized in dermato-oncology, the field of dermatoimmunology comprising inflammatory skin diseases is only at the step from traditional toward stratified medicine. This lack of innovation leaves clinically relevant questions unanswered, including predicting the personal likelihood of therapeutic success as well as the risk of drug-related adverse events or the development of comorbidities. The translational dermatology initiative hypothesizes that these shortcomings are due to the subjective nature of the current disease ontology, which does not address the heterogeneity and dynamics of diseases. By integrating deep clinical phenotyping and repetitive multiomics analyses of tissue and circulation of patients covering the whole spectrum of chronic skin inflammation independent of the traditional disease nomenclature, the translational dermatology initiative creates a high-quality dataset optimized for machine learning. The aim of the translational dermatology initiative is to reclassify inflammatory skin diseases on the basis of objective molecular events that enable prediction of clinically meaningful outcome variables. The translational dermatology initiative is currently recruiting at 2 centers (Freiburg and Stockholm), with the aim to expand this into a global initiative.

PMID:40535547 | PMC:PMC12173067 | DOI:10.1016/j.xjidi.2025.100381

J Pediatr Pharmacol Ther. 2025 Jun;30(3):372-375. doi: 10.5863/JPPT-24-00015. Epub 2025 Jun 9.

ABSTRACT

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and potentially life-threatening syndrome. Herein, we present the case of a 14-year-old female who developed a diffuse erythematous rash with fever and facial edema 6 weeks after initiating treatment with carbamazepine and sertraline. Laboratory tests showed an inflammatory reaction, elevated liver enzymes, and mild eosinophilia. Serology tests were negative for viral hepatitis, cytomegalovirus, herpes simplex virus, and parvovirus B19, but positive anti-VCA IgM and anti-EBNA IgG confirmed the presence of Epstein-Barr virus reactivation. Drugs were withdrawn, and the patient was treated with corticosteroid. Carbamazepine was identified as the culprit drug after performing patch tests. Even though DRESS is rare in childhood, we present another case of carbamazepine-induced DRESS in an adolescent associated with EBV activation.

PMID:40534938 | PMC:PMC12172683 | DOI:10.5863/JPPT-24-00015

Front Immunol. 2025 Jun 4;16:1586361. doi: 10.3389/fimmu.2025.1586361. eCollection 2025.

ABSTRACT

OBJECTIVE: To comprehensively analyze the safety profile of Methotrexate in clinical use, clarify the incidence of adverse reactions and associated influencing factors, and provide evidence for safe medication practices in clinical settings.

METHODS: This study retrieved data from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2024. Data filtering was conducted on the main suspect drug. Data extraction and cleaning were performed using R software, and various statistical methods, including ROR (Reporting Odds Ratio), PRR (Proportional Reporting Ratio), BCPNN (Bayesian Confidence Propagation Neural Network), and MGPS (Multi-Item Gamma Poisson Shrinker), were employed to detect adverse drug reaction signals. Subgroup analyses based on gender, age, and reporter categories were performed to explore differences.

RESULTS: A total of 130,818 methotrexate (MTX)-related adverse event (AE) reports were included. Females accounted for 64.2% of reporters, with adults aged 18-64.9 years reporting the most. AEs primarily affected the immune, musculoskeletal, and hematologic systems. "General Disorders and Administration Site Conditions" was the most frequently reported system organ class [n=106,183, ROR (95% CI)=1.21 (1.21-1.22)], while "Immune System Disorders" showed the strongest signal [n=13,313, ROR (95% CI)=2.35 (2.31-2.39)]. Adverse reactions varied by gender and age: females were more likely to report Drug Hypersensitivity [n=6,192, ROR (95% CI)=4.69 (4.57-4.82)], while males reported Nausea more often [n=1,624, ROR (95% CI)=1.17 (1.12-1.23)]. Elderly patients (≥65 years) had an increased risk of drug hypersensitivity [n=2,894, ROR (95% CI)=7.91 (7.61-8.22)]. Reporting priorities differed: consumers frequently reported "Drug Ineffective" [n=5,729, ROR (95% CI)=2.24 (2.18-2.3)] and "Pain" [n=1,746, ROR (95% CI)=1.69 (1.61-1.77)], while healthcare professionals focused on DRUG INEFFECTIVE [n=9,982, ROR (95% CI)=4.16 (4.08-4.25)]. Additionally, the time to onset of MTX-induced AEs varied significantly across subgroups.

CONCLUSION: This study reveals the safety characteristics of MTX in clinical use, confirms known adverse reactions, and identifies new potential adverse effects. It suggests that clinicians should enhance monitoring based on patient factors such as gender and age, particularly for immune system-related adverse reactions in elderly patients. Moreover, the spectrum of MTX's side effects may be broader than previously recognized, warranting further research to ensure patient safety in drug use.

PMID:40534848 | PMC:PMC12174053 | DOI:10.3389/fimmu.2025.1586361

Cerebellum. 2025 Jun 18;24(4):119. doi: 10.1007/s12311-025-01873-4.

ABSTRACT

Omaveloxolone, the first approved therapeutic agent for Friedreich ataxia (FRDA), currently has limited real-world safety data available. This study aims to evaluate post-marketing adverse events (AEs) associated with its clinical use by analyzing data from the FDA Adverse Event Reporting System (FAERS). We collected all adverse reaction reports associated with omaveloxolone from the first quarter of 2023 (Q1 2023) to the fourth quarter of 2024 (Q4 2024) in the FAERS database and performed signal detection using four distinct pharmacovigilance methods: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). A total of 9,326,057 AE reports were collected, among which 820 reports were associated with omaveloxolone. All AEs were categorized into 25 System Organ Classes (SOCs) and 67 positive Preferred Terms (PTs). Investigations represented the most frequently reported SOC, followed by gastrointestinal disorders and general disorders and administration site conditions. Hepatic enzyme increased emerged as the most prominent adverse event, demonstrating both high reporting frequency and strong signal intensity, primarily manifesting as elevated ALT and AST levels. Other commonly reported AEs included fatigue, nausea, headache, and blood cholesterol increased. The study also identified several novel potential AEs, such as urinary tract infection, diabetes mellitus, urine odour abnormal, atrial flutter, and urosepsis. Although some of these AEs were reported in relatively low frequencies, their clinical severity and elevated signal strengths suggest that omaveloxolone may potentially affect patients' urinary and endocrine systems, warranting particular attention during clinical administration. In conclusion, while omaveloxolone demonstrates multifaceted benefits in improving neurological function in patients with FRDA, its clinical application necessitates comprehensive evaluation of potential risks, and the development of safe and rational therapeutic strategies is crucial for optimizing treatment outcomes.

PMID:40533692 | DOI:10.1007/s12311-025-01873-4

Nervenarzt. 2025 Jun 18. doi: 10.1007/s00115-025-01831-9. Online ahead of print.

ABSTRACT

BACKGROUND: The use of psychoactive substances is associated with the risk of somatic complications requiring treatment. Psychiatric consultations can be requested in this context.

AIM: Description of physical and psychological complications of acute and chronic use of various drugs (except alcohol and benzodiazepines), and the procedure for consultations.

MATERIALS: Narrative literature review.

RESULTS: Severe physical and psychological complications of drug use can also occur with sporadic use. New psychoactive substances (NPS) in particular are known to have severe side effects compared to plant-based drugs with similar effects. Sporadic drug use, harmful use, and dependence must be differentiated diagnostically. Somatic complications of chronic use usually occur with dependent use, especially with intravenous drug administration. Depending on the individual case, recommendations for abstinence, safer use, or motivational interventions to take up a subsequent support program should be made. This requires precise knowledge of the local treatment network for drug users. Medication is used to alleviate withdrawal symptoms symptomatically. Potential complications must be taken into account during withdrawal treatment, e.g. withdrawal delirium and seizures in the case of GABA-ergic drugs. Maintenance treatment is the therapy of choice for opioid addicts.

CONCLUSION: Addiction psychiatry consultations should not only offer help in the management of current clinical problems, but should also show those affected the possibilities of further care and treatment.

PMID:40531322 | DOI:10.1007/s00115-025-01831-9

Emergencias. 2025 Jun;37(3):196-202. doi: 10.55633/s3me/025.2025.

ABSTRACT

OBJECTIVE: Objective. Adverse drug events (ADEs) are a well-known cause for emergency department visits. The objective of this study is to evaluate the prevalence of these adverse events through an annual multicentcer cross-sectional registry and identify factors associated with new emergency visits within 30 days following discharge.

METHODS: We conducted a multicenter cross-sectional study in emergency departments of Spanish hospitals. The identification and registration of patients were obtained from the census of patients treated in emergency departments at the end of the of the 5-year registry period. We used a multivariate logistic regression model to evaluate possible risk factors for new emergency visits within 30 days of discharge.

RESULTS: A total of 10,678 patients were evaluated in 53 centers, 785 of whom (7.35%) consulted due to ADEs. Prevalence ranged from 0% up to 14.3%. Antithrombotic drugs were the therapeutic group responsible for the highest number of events, causing 96 of them (25.9%). Regarding AEs, hemorrhagic events (n = 63; 8.1%), followed by episodes of confusion (n = 42; 5.4%), were the most common ones. A total of 86 (23.5%) evaluable patients returned to the emergency department within 30 days of discharge. Chronic prescription of > 10 drugs was associated with a higher risk of new consultations [OR, 1.65 (1.07-2.56)].

CONCLUSIONS: ADEs are a common reason for emergency department visits and are associated with a significant number of subsequent visits after discharge. Severe polypharmacy is a risk factor for new emergency visits within 30 days.

PMID:40531119 | DOI:10.55633/s3me/025.2025

Emergencias. 2025 Jun;37(3):186-195. doi: 10.55633/s3me/026.2025.

ABSTRACT

OBJECTIVE: To describe and compare the diagnosis associated with medication-related problems (MRP) that lead to emergency departments visits based on sex and type of culprit drug.

METHODS: We conducted a retrospective observational study included 1,611 adult patients who visited the emergency department of a tertiary referral center in Catalonia (Spain) from 2021 through 2022 for MRP. We collected sociodemographic and clinical baseline variables in addition to the diagnosis and drug associated with the MRP that caused the visit to the emergency department based on the medical history at discharge. Data analysis was performed using binomial distribution tests and binary logistic regression models.

RESULTS: More than 50% of patients who visit the emergency department for MRP are women (95%CI, 55%-60%). Additionally, as age increases, the percentage of women visiting the emergency department rises significantly vs men (P .001). Significant differences by sex were found in the MRP-related diagnosis and the type of culprit drug. The frequency of women with MRP associated with diarrhea and decreased intestinal motility was higher (P .001), as well as unintentional drug poisonings (P = .001), hypertension (P = .010), hyponatremia (P .001), and hypokalemia (P = .001). Women visit the emergency department more than men do regarding MRP associated with drugs acting on the nervous, cardiovascular, and anti-infective systems (P .001).

CONCLUSIONS: Results highlight sex differences and justify the need to continue researching to minimize such differences.

PMID:40531118 | DOI:10.55633/s3me/026.2025

Eur J Neurol. 2025 Jun;32(6):e70256. doi: 10.1111/ene.70256.

ABSTRACT

BACKGROUND AND PURPOSE: Movement disorders are increasingly recognized as late-occurring neurologic manifestations of 22q11.2 deletion syndrome (22q11.2DS). We aimed to dissect the spectrum of relevant movement disorders in 22q11.2DS, including clinical and electrophysiologic presentations and effective therapies.

METHODS: Retrospective review of medical records, medication histories, and videotaped examinations was conducted in 31 unrelated adults (55% female) diagnosed with 22q11.2DS and a movement disorder who were seen at a major center of excellence from June 1996 to September 2023. Between-group comparisons were performed to explore the influence of medications on movement disorder presentations.

RESULTS: The median age at movement disorder onset was 35.5 (IQR: 22.0) years. Non-parkinsonian tremor was the most common phenotype (21/31, 68%), followed by parkinsonism (13/31, 42%), dystonia (11/31, 36%), myoclonus (9/31, 29%), dyskinesia (6/31, 19%), stereotypies, and functional movement disorders (4/31, 13% each). The majority of patients (24/31, 77%) presented with two or more movement disorder phenotypes (median 3, range: 2-7). Similar trends in prevalence emerged after accounting for antipsychotic exposure and potential drug-related movement disorders. Electrophysiological assessments identified both previously described and novel motor phenotypes. Treatment data for at least one movement disorder (available for 20/31, 65%) indicated a positive response to standard phenotype-based interventions.

CONCLUSIONS: We demonstrate that movement disorders in adults with 22q11.2DS exhibit greater clinical complexity than previously reported, which could reflect innate vulnerability and pathologic mechanisms beyond medication side effects. In those with a confirmed 22q11.2 microdeletion, periodic neurologic evaluations, supported by electrophysiologic investigations, enable accurate diagnosis and implementation of personalized management strategies.

PMID:40530538 | DOI:10.1111/ene.70256