Artif Intell Med. 2025 Jan;159:103029. doi: 10.1016/j.artmed.2024.103029. Epub 2024 Nov 20.

ABSTRACT

Predicting drug-drug interactions (DDIs) is crucial for understanding and preventing adverse drug reactions (ADRs). However, most existing methods inadequately explore the interactive information between drugs in a self-supervised manner, limiting our comprehension of drug-drug associations. This paper introduces EDDINet: Enhancing Drug-Drug Interaction Prediction via Information Flow and Consensus-Constrained Multi-Graph Contrastive Learning for precise DDI prediction. We first present a cross-modal information-flow mechanism to integrate diverse drug features, enriching the structural insights conveyed by the drug feature vector. Next, we employ contrastive learning to filter various biological networks, enhancing the model's robustness. Additionally, we propose a consensus regularization framework that collaboratively trains multi-view models, producing high-quality drug representations. To unify drug representations derived from different biological information, we utilize an attention mechanism for DDI prediction. Extensive experiments demonstrate that EDDINet surpasses state-of-the-art unsupervised models and outperforms some supervised baseline models in DDI prediction tasks. Our approach shows significant advantages and holds promising potential for advancing DDI research and improving drug safety assessments. Our codes are available at: https://github.com/95LY/EDDINet_code.

PMID:39608043 | DOI:10.1016/j.artmed.2024.103029

J Biomech. 2024 Dec;177:112421. doi: 10.1016/j.jbiomech.2024.112421. Epub 2024 Nov 9.

ABSTRACT

While levodopa is the most effective drug for symptom treatment of Parkinson's Disease (PD), its long-term use often leads to side effects such as uncontrolled involuntary movements known as levodopa-induced dyskinesia (LID). LID has been shown to increase postural sway, but the extent to which these hyperkinetic movements alter postural sway strategies has not been explored. We recruited 25 people with idiopathic PD, of which 13 exhibit clinical signs of LID, and 10 healthy older adults. Participants performed thirty-second standing trials with no added task (single-task) and with performing a cognitive dual-task, known to provoke dyskinesia. Participants with PD were tested in their practical OFF and ON states. The root-means-square (RMS) accelerations were obtained from inertial sensors attached to the lumbar, trunk, and head. Sway ratios (superior-to-inferior segment) were calculated to determine the effect of LID on postural sway strategies. Participants with LID showed greater RMS head sway, compared to those without LID and older adults. The head-to-trunk sway ratio was greater in participants with LID during the ON state or when dual-tasking. In addition, the head-to-lumbar sway ratio was greater in participants with LID in the ON state during both single- and dual-tasking. Our results reveal an altered postural control strategy in PD with LID, presenting increased sway in superior segments of the kinematic chain, leading to head instability. Unlike PD without LID and older adults, PD with LID exhibit multi-link sway in the ON state, which has important implications for measuring postural sway in the presence of dyskinesias.

PMID:39608183 | DOI:10.1016/j.jbiomech.2024.112421

Yonsei Med J. 2024 Dec;65(12):695-702. doi: 10.3349/ymj.2024.0180.

ABSTRACT

PURPOSE: Intravenous (IV) acetaminophen-induced hypotension is a clinically significant issue that remains difficult to predict. Therefore, this study aimed to identify the factors associated with hypotension in patients with repeated IV acetaminophen administration.

MATERIALS AND METHODS: This observational cohort study included patients who received IV acetaminophen in the critical care unit of the Yongin Severance Hospital in 2020. All IV acetaminophen administration records for each patient were reviewed, and the blood pressure records within 2 h after IV acetaminophen administration were examined. Changes in blood pressure within 2 h of IV acetaminophen administration were monitored to identify hypotension, defined as a systolic blood pressure <90 mm Hg, a decrease in systolic blood pressure by 30 mm Hg, or a decrease in mean arterial pressure by 15%.

RESULTS: There were 1547 instances of IV acetaminophen administration among 398 patients. Of these, 416 instances (26.9%) resulted in hypotension among 204 patients (51.3%). A history of IV acetaminophen-induced hypotension did not predict subsequent hypotensive episodes, and there was no consistent tendency. The use of beta-blocker [odds ratio (OR)=1.50], gastrointestinal (GI) infection (OR=1.42), and septic shock (OR=1.68) were significant risk factors for IV acetaminophen-induced hypotension in multivariate analysis. In subgroup analysis of cases with beta-blocker, heart failure (OR=1.91), urinary tract infection (OR=2.16), GI infection (OR=1.83) were significant risk factors.

CONCLUSION: Severe infections, heart failure, and the use of beta-blockers are associated with IV acetaminophen-induced hypotension. However, IV acetaminophen-induced hypotension is inconsistent and depends on the patient's condition.

PMID:39609085 | DOI:10.3349/ymj.2024.0180

Drug Ther Bull. 2024 Nov 28:dtb-2024-000067. doi: 10.1136/dtb.2024.000067. Online ahead of print.

NO ABSTRACT

PMID:39608987 | DOI:10.1136/dtb.2024.000067

Drug Ther Bull. 2024 Nov 28;62(12):178. doi: 10.1136/dtb.2024.000024.

NO ABSTRACT

PMID:39608984 | DOI:10.1136/dtb.2024.000024

Med Klin Intensivmed Notfmed. 2024 Nov 28. doi: 10.1007/s00063-024-01214-z. Online ahead of print.

ABSTRACT

Critically ill patients are at high risk of adverse drug-drug interactions. Pharmacodynamic drug-drug interaction may cause organ damage. Pharmacokinetic interactions are usually caused by inhibition or induction of enzymes of drug metabolism such as cytochrome P-450 isoenzymes or transporter proteins such as P‑glycoprotein. Inhibitors of such molecules can cause toxic levels of the corresponding substrates, while inducers might produce subtherapeutic concentrations. Amiodarone, macrolides, antifungal azoles, direct-acting anticoagulants, vitamin K antagonists, immunosuppressants, rifampicin, and some central nervous system (CNS)-active substances are frequently involved in drug-drug interactions. Sound risk and benefit assessment of the applied medication, therapeutic drug monitoring, the use of electronic alert systems and databases along with clinical evaluation will contribute to avoiding adverse drug-drug interactions.

PMID:39607462 | DOI:10.1007/s00063-024-01214-z

Cureus. 2024 Oct 28;16(10):e72524. doi: 10.7759/cureus.72524. eCollection 2024 Oct.

ABSTRACT

Drug-induced neuropsychiatric symptoms are not uncommon, particularly in patients with multiple comorbidities and polypharmacy. Sacubitril/valsartan is a combination medication used in the treatment of heart failure, especially for reducing hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF). However, its neurological side effects, including delirium, hallucinations, and confusion, have been increasingly reported. This case report explores the occurrence of drug-induced delirium, specifically visual hallucinations, in a 79-year-old male with HFpEF and end-stage kidney disease (ESKD) after starting sacubitril/valsartan.

PMID:39606515 | PMC:PMC11600233 | DOI:10.7759/cureus.72524

Open Forum Infect Dis. 2024 Nov 12;11(12):ofae672. doi: 10.1093/ofid/ofae672. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: The prevention of perinatal human immunodeficiency virus (HIV) transmission depends on the safe and effective use of antiretroviral therapy (ART). Simplifying treatment reduces drug exposure for both mother and child. We evaluated the safety and efficacy of dolutegravir (DTG) plus lamivudine (3TC) for antiretroviral-naive pregnant women with HIV.

METHODS: This proof-of-concept trial enrolled ART-naive pregnant women ≥15 years old with HIV infection and a gestational age between 14 and 28 weeks. Participants received a fixed-dose combination of DTG/3TC. Baseline HIV genotyping was performed. Participants were monitored at baseline, every 4 weeks, and at delivery. Infants were assessed at birth, 4 weeks, and 6 weeks of age. Outcomes included the proportion of women achieving an undetectable HIV type 1 plasma viral load (<50 copies/mL) at delivery, therapy modification frequency, perinatal HIV transmission rate, and adverse events.

RESULTS: Between January 2019 and March 2021, 20 women were enrolled. At baseline, the median CD4 cell count was 401.6 ± 113.6 cells/μL, increasing to 690.2 ± 266 cells/μL at delivery. Median viral load was 9514 copies/mL. All women achieved an undetectable viral load after an average of 40 days. No cases of perinatal HIV transmission were detected. No therapy modifications were necessary during the study, and no adverse events were related to the ART.

CONCLUSIONS: In this pilot trial, DTG/3TC demonstrated safety and efficacy, with all participants achieving viral suppression before delivery. There were no cases of perinatal HIV transmission and no drug-related adverse events. DTG/3TC can be an option for initial treatment of drug-naive pregnant women with HIV.

PMID:39605976 | PMC:PMC11600954 | DOI:10.1093/ofid/ofae672

Ophthalmol Sci. 2024 Sep 30;5(1):100627. doi: 10.1016/j.xops.2024.100627. eCollection 2025 Jan-Feb.

ABSTRACT

OBJECTIVE: To investigate the effects of oral baricitinib on ocular surface disease (OSD) in patients with chronic graft-versus-host disease (cGVHD).

DESIGN: Prospective phase 1 to 2 single institution trial.

SUBJECTS: Eighteen patients with ocular graft-versus-host-disease (oGVHD) and systemic steroid-refractory cGVHD.

METHODS: Oral baricitinib (2 mg and 4 mg) was administered daily for up to 12 months in an intrapatient dose-escalation design. National Institutes of Health (NIH) oGVHD score, vision, corneal Oxford staining (COS), tear break-up time (TBUT), Schirmer I test (ST) without anesthesia, and microliter tear equivalent conversion were assessed at baseline, 6 months (primary efficacy end point), and 12 months if patients remained on the drug.

MAIN OUTCOME MEASURES: Improvement in NIH oGVHD score, COS, TBUT, and ST results in patients with and without conjunctival fibrosis at 6 months.

RESULTS: At 6 months, the NIH oGVHD score significantly improved (P = 0.014) with all OSD parameters also showing improvement, though not statistically significant. COS baseline, 2.17 to 0.95; TBUT baseline, 6.66 to 8.18 seconds, Schirmer I baseline, 3.86 mm (2.6 μl) to 5.56 mm (3.9 μl). For patients continuing treatment at 12 months improvements persisted compared with the baseline but remained statistically nonsignificant. Corneal Oxford staining decreased to 0.94; TBUT increased to 8.95 seconds, and ST improved to 10.19 mm (7.2 μL). Conjunctival fibrosis was present in 39% (n = 7) of the patients at baseline. The greatest improvement was observed in the 11 patients without prior conjunctival fibrosis compared with the baseline: COS 1.84, TBUT 6.32 seconds, ST 4.07 mm (2.1 μl); 6 months: COS 0.25 (P = 0.018), TBUT 8.62 seconds, ST 9.12 mm (5.4 μl); 12 months: COS 0, TBUT 10.29 seconds, ST 16.88 mm (10.6 μl). Vision was stable in all groups. Two patients developed asymptomatic, self-limited conjunctival papillomas, and 1 patient developed uncomplicated bacterial conjunctivitis twice. No dose limiting toxicity was observed. Severe adverse events with hospitalizations for possible drug-related systemic infections occurred in 5 patients.

CONCLUSIONS: Systemic baricitinib was well-tolerated, improved NIH oGVHD scores and OSD parameters in patients with oGVHD, with the greatest benefits observed in patients without pre-existing conjunctival fibrosis. Conjunctival fibrosis may affect outcomes and should be considered in patient selection for clinical trials.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PMID:39605875 | PMC:PMC11599446 | DOI:10.1016/j.xops.2024.100627

Radiologia (Engl Ed). 2024 Oct;66 Suppl 2:S98-S109. doi: 10.1016/j.rxeng.2024.03.012. Epub 2024 Nov 14.

ABSTRACT

Radiological contrast media, both iodinated and gadolinium-based, can lead to adverse reactions. Type A reactions are related to the pharmacological characteristics of the contrast, including side, secondary and toxic effects. Post-contrast acute kidney injury is the most frequent adverse reaction to iodinated contrast media. Less frequently, thyroid, neurological, cardiovascular, haematological, and salivary gland effects are also detected. With gadolinium-based contrast agents, nausea is the most frequent reaction, but there is also a risk of producing nephrogenic systemic fibrosis and cerebral deposits of uncertain significance. The most effective way of avoiding type A reactions is to decrease the dose and frequency of contrast media administration, especially in patients with pre-existing renal insufficiency. To prevent post-contrast acute kidney injury, adequate hydration of the patient should be maintained orally or intravenously, avoiding prolonged periods of liquid fasting. On the other hand, hypersensitivity reactions are dose-independent and clinically can range from mild cutaneous reactions to anaphylaxis. This article proposes an algorithm that differentiates between nonspecific reactions and true hypersensitivity reactions, as well as levels of severity. It also provides a treatment scheme for immediate reactions adjusted to the severity level, with a focus on the management of anaphylaxis and an early intramuscular administration of adrenaline. Finally, it sets out recommendations for the management of patients with previous hypersensitivity reactions who require elective or urgent contrast administration, favouring the use of alternative contrast media with confirmed tolerance instead of the indiscriminate use of premedication.

PMID:39603745 | DOI:10.1016/j.rxeng.2024.03.012

J Biomed Inform. 2024 Nov 25:104752. doi: 10.1016/j.jbi.2024.104752. Online ahead of print.

ABSTRACT

OBJECTIVE: The objectives of this study were to: (1) create a corpus of synthetic drug-related patient portal messages to address the current lack of publicly available datasets for model development, (2) assess differences in language used and linguistics among the synthetic patient portal messages, and (3) assess the accuracy of patient-reported drug side effects for different racial groups.

METHODS: We leveraged a taxonomy for patient- and clinician-generated content to guide prompt engineering for synthetic drug-related patient portal messages. We generated two groups of messages: the first group (200 messages) used a subset of the taxonomy relevant to a broad range of drug-related messages and the second group (250 messages) used a subset of the taxonomy relevant to a narrow range of messages focused on side effects. Prompts also include one of five racial groups. Next, we assessed linguistic characteristics among message parts (subject, beginning, body, ending) across different prompt specifications (urgency, patient portal taxa, race). We also assessed the accuracy and frequency of patient-reported side effects across different racial groups and compared to real world data.

RESULTS: The study generated 450 synthetic patient portal messages, and we assessed linguistic patterns, accuracy of drug-side effect pairs, frequency of pairs compared to real world data. Linguistic analysis with LIWC revealed variations in language usage and politeness and analysis of positive predictive values identified differences in symptoms reported based on urgency levels and racial groups in the prompt. We also found similar levels of drug-side effect pair occurrence to the SIDER database.

CONCLUSION: This study demonstrates the potential of synthetic patient portal messages as a valuable resource for healthcare research. After creating a corpus of synthetic drug-related patient portal messages, we identified significant language differences and evaluated the accuracy and frequency of drug-side effect pairs across various prompts.

PMID:39603549 | DOI:10.1016/j.jbi.2024.104752

J Clin Med. 2024 Nov 13;13(22):6820. doi: 10.3390/jcm13226820.

ABSTRACT

Background: This study aimed to provide a comprehensive analysis of 56 patients admitted to the Lung Cancer Clinical Care Center (C3) at Fundación Santa Fe de Bogotá (FSFB) between 2 May 2022 and 22 April 2024. The focus was on demographic characteristics, smoking history, comorbidities, lung cancer types, TNM classification, treatment modalities, and outcomes. Methods: This observational case series study reviewed medical records and included patients over 18 years with a confirmed diagnosis of non-small cell lung cancer (NSCLC). Data were collected and analyzed for demographics, comorbidities, treatment types, biomolecular profiling, and survival rates. Ethical approval was obtained, and data were anonymized. Results: The mean age was 71.8 years with a female predominance (53.6%). A history of smoking was present in 71.4% of patients. Adenocarcinoma was the most common type (75.0%), followed by squamous cell carcinoma (19.6%). At admission, the most frequent TNM stages were IA2 (17.9%) and IVA (16.1%). One-year survival was 68.8%, and 94.3% of stage I-IIIA patients underwent PET scans. Biomolecular profiling revealed 69.2% non-mutated EGFR, 90.4% ALK-negative, and various PDL-1 expression levels. Immunotherapy was received by 91.4% of patients, with Alectinib and Osimertinib being common. Grade III-IV pneumonitis occurred in 5.4% of patients. Conclusions: The study's findings align with existing literature, highlighting significant smoking history, common adenocarcinoma, and substantial use of immunotherapy. Limitations include the observational design, small sample size, and short follow-up period, impacting the generalizability and long-term outcome assessment. Future research should address these limitations and explore longitudinal outcomes and emerging therapies.

PMID:39597963 | DOI:10.3390/jcm13226820

Medicina (Kaunas). 2024 Oct 22;60(11):1728. doi: 10.3390/medicina60111728.

ABSTRACT

Background and Objectives: Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease characterized by recurrent febrile attacks and serosal inflammation. The goals of FMF treatment are to prevent acute attacks and the development of amyloidosis. This study aimed to investigate the benefit of switching to compressed colchicine tablets in patients with FMF who are resistant or intolerant to the pharmaceutical preparation of coated colchicine tablets in terms of attack frequency and side effects. Materials and Methods: Patients who developed resistance and intolerance under coated colchicine tablet treatment and, therefore, switched to compressed colchicine tablets were identified. The attack frequencies and drug-related side effects in patients using the two different pharmaceutical colchicine preparations were compared. Results: The mean age of the 172 patients treated with compressed tablets alone following coated tablets was 36.3 ± 11.4 years, and 75 (43.6%) were male. The most common genetic mutation was detected as M694V in 111 (64.5%) patients, and 36 (20.9%) of them were homozygous. A decrease in the daily colchicine dose was found after switching to compressed colchicine tablets in patients followed for 7 years (2.1 ± 0.7 mg vs. 1.7 ± 0.5 mg; p < 0.001). Episodes lasted for one to three days and then resolved spontaneously. After treatment with the compressed tablet form of colchicine, 129 (75%), 33 (19%), and 10 (6%) patients had 0-3, 4-6, and more than 7 attacks, respectively (p < 0.001). Diarrhea and aminotransferase elevation, the most common side effects in patients using coated colchicine tablets, decreased after using compressed colchicine tablets (p < 0.001). Conclusions: Compressed colchicine tablets were shown to be effective in patients who did not respond to coated colchicine therapy and those with pre-treatment intolerance to biological agents.

PMID:39596913 | DOI:10.3390/medicina60111728

Cancers (Basel). 2024 Nov 8;16(22):3773. doi: 10.3390/cancers16223773.

ABSTRACT

BACKGROUND: Everolimus at 10 mg daily is approved to treat patients with advanced grade 1/2 neuroendocrine tumors (NETs), although it may lead to significant toxicity. Grade 3 or higher drug-related adverse events and drug discontinuation occur in approximately one-fourth of cases. However, phase I trials have demonstrated that doses from 5 mg daily efficiently inhibit NET cell signaling.

OBJECTIVES AND METHODS: This multicenter retrospective study compared the time to treatment failure (TTF) in patients with NETs who received a mean daily dose of 7-10 mg (higher dose [HD]) or ≤6 mg (lower dose [LD]) of everolimus.

RESULTS: Ninety-two patients were included: 74 (80%) in the HD group and 18 (20%) in the LD group. At a median follow-up of 4.2 years, the median time to treatment failure (TTF) was 9.2 months for the HD and 7.2 months for the LD groups (p = 0.85). The TTF did not significantly differ between the LD and the HD groups (HR: 1.24; 95% CI: 0.68-2.25; p = 0.47), even after adjusting for age at treatment initiation, the NET grade, and the treatment line.

CONCLUSION: Everolimus doses from 5 to 6 mg/day seem to be equally as effective as higher doses, but lower doses are potentially associated with less toxicity and lower costs. These findings support validation through a randomized clinical trial.

PMID:39594728 | DOI:10.3390/cancers16223773

Ocul Immunol Inflamm. 2024 Nov 26:1-8. doi: 10.1080/09273948.2024.2430709. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the barriers to adherence with immunomodulatory therapy (IMT) for patients with uveitis across multiple regions of the United States.

METHODS: A multi-center survey of adult and pediatric patients with ocular inflammatory diseases undergoing treatment with IMT was conducted between September 2021 and August 2022. Participating sites included Johns Hopkins Wilmer Eye Institute, Wong Eye Institute of the University of Texas at Austin, University of Wisconsin-Madison, University of Minnesota, Veterans Affairs Hospital of Minneapolis, and Washington University of St. Louis. Each patient completed a self-reporting survey to identify barriers to adherence.

RESULTS: The survey was completed by 98 subjects, of whom were 71% white, 67% female, and 61% had a college or advanced degree. Nearly half (49%) were on two or more IMTs of which the most common were methotrexate (38%), mycophenolate (36%), or adalimumab (36%). Nearly half (52%) of patients required reminders to take their medications and 20% found it difficult to take IMT regularly, with 12% struggling to take medications multiple times a day. A lack of refills resulted in 15% of patients missing doses. Limitations to completing laboratory studies to monitor for drug-related side-effects included finding time (10%) and cost (22%).

CONCLUSION: Barriers to IMT treatment include laboratory study cost, difficulty with medication administration, and adhering to medication schedules. Monthly cost of medication was high for some, but no patients were unable to take IMT due to insurance loss. Addressing these barriers may improve IMT adherence for uveitis patients and better clinical outcomes.

PMID:39591521 | DOI:10.1080/09273948.2024.2430709

PLoS One. 2024 Nov 26;19(11):e0314023. doi: 10.1371/journal.pone.0314023. eCollection 2024.

ABSTRACT

Patients' safety can be compromised in the transition of care between healthcare sectors. Optimal information flow across healthcare sectors and individualized medication treatment tailored to each patient is vital to prevent adverse events like drug-related problems. When medication changes are made during hospitalization, it is essential to ensure that the relevant general practitioner (GP) is included in the communication chain. This randomized controlled trial examines the effect of a Medication Coordinator who facilitates medication reviews in close collaboration with patients using My Medication Plan. Patients in the intervention group receive the medication review in combination with including suggested medication amendments documented in their electronic discharge letter send, which is sent to their GP. The patients randomized to the control group receive standard care by the ward staff. Seventy patients from the Endocrinology and Nephrology Unit at the Hospital Sønderjylland will be included in the intervention and control groups, respectively. The primary outcome is the proportion of potentially inappropriate medications. Secondary outcomes include patient-reported outcomes, i.e., quality of life and medication burden. Additional outcomes include the patient's medication risk score, whether the patient is readmitted, and whether the patient has contacted the staff at the hospital unit after the hospital discharge. The framework for complex intervention is applied, because it allows flexibility and adaption in meeting patients' needs by implementing tailored, possibly complex interventions in different healthcare settings. This project will examine a particular piece in the puzzle of the complexity of conducting a medication review and communication of suggested medication amendments to the patients, healthcare at the hospital, and the GP. Hopefully, this can contribute to a reduction in the risk of potentially inappropriate post-hospital medication usage. Trial registration: The study has been registered at ClinicalTrial.gov with the registration number: NCT06383364. https://clinicaltrials.gov/study/NCT06383364.

PMID:39591420 | DOI:10.1371/journal.pone.0314023

Hum Vaccin Immunother. 2024 Dec 31;20(1):2429237. doi: 10.1080/21645515.2024.2429237. Epub 2024 Nov 26.

ABSTRACT

Immunotherapy has emerged as a crucial advancement in pulmonary carcinoma treatment. Nevertheless, its unique side effects not only reduce patients' quality of life but also affect treatment efficacy, with severe cases potentially endangering the patient's life. This study uses bibliometric analysis to perform a comprehensive bibliometric analysis literature on IRAEs in lung cancer from 1991 to 2023, retrieved from the Web of Science database. The dataset was analyzed using VOSviewer and CiteSpace to identify trends, key contributors, and emerging research areas. A total of 124 publications were analyzed, revealing a notable increase in research activity post-2015, with China and the USA contributing over 50% of the studies. This research highlights the importance of understanding IRAEs and suggests future investigations into the pulmonary microbiota and tumor microenvironment.

PMID:39588915 | DOI:10.1080/21645515.2024.2429237

Breast Cancer (Auckl). 2024 Nov 25;18:11782234241301314. doi: 10.1177/11782234241301314. eCollection 2024.

ABSTRACT

Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, is crucial in treating hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic or recurrent breast cancer. However, its association with drug-induced interstitial lung disease (DI-ILD) is concerning. We present an 82-year-old woman with breast cancer receiving abemaciclib, who developed persistent cough and malaise. Initial diagnostics suggested pneumonia, supported by ground-glass opacities and consolidations on chest high-resolution computed tomography. Suspecting DI-ILD, a transbronchial lung cryobiopsy (TBLC) was performed, revealing fibrosing organizing pneumonia and confirming abemaciclib-induced ILD. Discontinuing abemaciclib led to significant symptom improvement, supporting the diagnosis. This case report describes the clinical presentation and diagnostic approach in a patient with suspected abemaciclib-induced ILD, including the use. To our knowledge, this is the first reported case of fibrosing organizing pneumonia as a histopathological pattern in abemaciclib-induced ILD, expanding knowledge of this therapy's pulmonary adverse events. Histopathological features included diffuse lymphocytic infiltration, polypoid intra-alveolar fibrosis, intraluminal granulation tissue plugs with dense hyalinization, hyalinized fibrotic alveolar septa lesions, and obliterative fibrotic processes affecting alveolar ducts. Our case suggests that TBLC might be useful in recognizing DI-ILD by providing detailed lung tissue examination, which can facilitate early diagnosis and guide management. Identifying fibrosing organizing pneumonia indicated a potentially corticosteroid-responsive pathology, suggesting a more favorable prognosis compared with patterns like diffuse alveolar damage. This case highlights the potential for abemaciclib-induced ILD to occur even after prolonged treatment periods, emphasizing the importance of vigilance and consideration of diagnostic intervention for patients on cyclin-dependent kinase 4/6 inhibitors presenting with respiratory symptoms. Timely recognition and appropriate management may mitigate adverse outcomes. Further studies are needed to confirm these findings and to better understand the role of TBLC and histopathological examination in diagnosing and managing abemaciclib-induced ILD.

PMID:39588010 | PMC:PMC11587177 | DOI:10.1177/11782234241301314

Crit Care. 2024 Nov 25;28(1):387. doi: 10.1186/s13054-024-05159-9.

ABSTRACT

BACKGROUND: The use of inhaled antibiotics for treating pneumonia in invasively ventilated patients offers a direct approach, allowing for high local concentrations of the drug in the lower respiratory tract while simultaneously reducing systemic toxicity. However, the real efficacy and safety of nebulized antibiotics remain unclear. The aim of the present is to assess among critically adult patients with pneumonia and invasive ventilation, whether receiving adjuvant inhaled antibiotics improves the rate of microbiological eradication.

METHODS: A comprehensive literature search of randomized clinical trials (RCTs) was conducted (from inception until September 20, 2024, PROSPERO-CRD592906) across Medline, Embase, and Scopus. Randomized controlled trials, enrolling intensive care units (ICU) patients with pneumonia and comparing nebulized antimicrobial therapy (inhaled group) with intravenous antimicrobial treatment or intravenous antimicrobial therapy plus inhaled placebo (control group), were included. The primary outcome was the rate of microbiological eradication after treatment. Secondary outcomes were the rate of clinical recovery, the incidence of drug-related adverse events, ICU and hospital mortality. A qualitative analysis was conducted according to the GRADE framework. Data were pooled using an odds-ratio analysis. The heterogeneity and reliability of our results were evaluated using the I2-statistic and trial sequential analysis (TSA), respectively.

RESULTS: A total of 11 RCTs (1472 patients) met the inclusion criteria. Compared to controls, the use of adjuvant inhaled antibiotics determined a greater rate of microbiological eradication (OR 2.63, 95% CI 1.36-5.09; low certainty of evidence). The TSA confirmed the reliability of our primary outcome. Moreover, nebulized antibiotics increased the risk of bronchospasm (OR 3.15, 95% CI 1.33-7.47; high evidence), while nephrotoxicity, clinical recovery, ICU and hospital survival (either in the case of pneumonia caused by MDR bacteria or not) were not different between groups.

CONCLUSIONS: In conclusion, compared to the sole intravenous therapy, the use of adjuvant inhaled antibiotics for treatment of pneumonia in invasively ventilated critically ill patients was associated with a greater incidence of microbiological eradication (low GRADE and high risk of publication bias), but not with clinical recovery and survival.

PMID:39587607 | DOI:10.1186/s13054-024-05159-9

Pharmacy (Basel). 2024 Nov 15;12(6):168. doi: 10.3390/pharmacy12060168.

ABSTRACT

Adverse drug events (ADEs) occur frequently and are a common cause of suffering, hospitalizations, or death, and can be caused by harmful combinations of medications. One method used to prevent ADEs is by using clinical decision support systems (CDSSs). Janusmed Risk Profile is a CDSS evaluating the risk for nine common or serious ADEs resulting from combined pharmacodynamic effects. The aim of this study was to examine the prevalence of potential ADEs identified using CDSS algorithms from Janusmed Risk Profile. This retrospective, cross-sectional study covered the population of a Swedish region (n = 246,010 inhabitants in year 2020) using data on all medications dispensed and administered. More than 20% of patients had an increased risk of bleeding, constipation, orthostatism, or renal toxicity based on their medications. The proportion of patients with an increased risk varied from 3.5% to almost 30% across the nine categories of ADEs. A higher age was associated with an increased risk of potential ADEs and there were gender differences. A cluster analysis identified groups of patients with an increased risk for several categories of ADEs. This study shows that combinations of medications that could increase the risk of ADEs are common. Future studies should examine how this correlates with observed ADEs.

PMID:39585094 | DOI:10.3390/pharmacy12060168