BMC Gastroenterol. 2025 Mar 7;25(1):148. doi: 10.1186/s12876-025-03732-2.

ABSTRACT

OBJECTIVE: With the rising incidence of MASLD, extensive drug research has been conducted in clinical trials. The study examined the design principles and research objectives of MASLD therapeutics, in order to offer guidance to clinical trial participants and decision makers.

METHODS: By searching the clinical research trial data registered on clinicaltrials.gov platform, 1209 interventional clinical trials were screened. These trials were subsequently evaluated based on clinical stage, trial design, intervention modalities, outcome metrics, and other pertinent factors.

RESULTS: A total of 1,209 trials were included, of which 199 were registered from 2000 to 2012 (16.46%) and 1010 were registered from 2013 to 2024 (83.54%), reflecting the growing body of research on MASLD. Regarding the intervention model type, single-group designs were employed in 232 (19.19%) trials, and parallel designs were employed in 873(72.21%). A total of 13 trials were early phase 1 (1.08%), 152 (12.57%) were phase 1, 34 (2.81%) were phase 1/phase 2, 301 were phase 2 (24.90%), 19 (1.57%) were phase 2/phase 3, 72 (5.96%) were phase 3, and 84 (6.95%) were phase 4. Within these trials, the three primary clinical outcomes for drug interventions were hepatic histological improvement, hepatic fat content and adverse events. Furthermore, 140 drug interventional trials with results for therapeutic purposes (This accounted for 88.61% of the 158 drug interventional trials with results) primarily aimed to improve MASLD through mechanisms such as metabolic and energy balance, inflammatory and immunomodulatory, and lipid reduction, targeting primarily PPAR, FXR, ACC and GLP-1.

CONCLUSION: This study suggests the basic characteristics of global MASLD clinical trial design, and the current global interventional clinical trials are mainly focused on drug-related treatments, and drugs to improve inflammation and metabolism are still the first choice for MASLD drug intervention studies.

PMID:40055604 | DOI:10.1186/s12876-025-03732-2

Lancet HIV. 2025 Mar;12(3):e191-e200. doi: 10.1016/S2352-3018(24)00344-8.

ABSTRACT

BACKGROUND: Long-acting cabotegravir and long-acting rilpivirine constitute a completely intramuscular antiretroviral therapy (ART) regimen for adults with HIV. We aimed to assess the safety, antiviral activity, and pharmacokinetics of oral cabotegravir and rilpivirine followed by a combination of long-acting cabotegravir and long-acting rilpivirine in virologically suppressed adolescents with HIV.

METHODS: The IMPAACT 2017/MOCHA study is a phase 1/2, multicentre, open-label, non-comparative, dose-finding trial being conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA. In cohort 2 of this study, adolescents (aged 12-18 years; weight ≥35 kg) with HIV and no serious comorbidities who were receiving stable combination ART with confirmed virological suppression and had either previously enrolled in the first cohort or had not previously participated in the study were eligible for inclusion. Participants stopped their background combination ART and received oral cabotegravir 30 mg once daily and oral rilpivirine 25 mg once daily orally for 4-6 weeks, followed by long-acting injectable cabotegravir 600 mg (3 mL) and long-acting injectable rilpivirine 900 mg (3 mL) intramuscularly at weeks 4 and 8, and every 8 weeks thereafter. The primary outcome was safety, including all adverse events, at week 24. Primary safety outcome measures were summarised as frequencies, percentages, and exact Clopper-Pearson 95% CIs in the evaluable analysis population, which included participants who were treated exclusively with the regimen and either completed all scheduled treatments or experienced severe adverse events, permanently discontinued the treatment, or died, whichever occurred first; and in the all-treated analysis population, which included all participants who received at least one dose of any study product. This study is registered with ClinicalTrials.gov (NCT3497676) and is ongoing.

FINDINGS: Between July 26, 2021, and Aug 27, 2022, 44 (80·0%) of 55 adolescents who participated in cohort 1 and 100 (87·0%) of 115 screened study-naive adolescents were enrolled in cohort 2. 74 (51·4%) participants were female and 70 (48·6%) were male. Overall, 15 (10·8% [95% CI 6·2-17·2]) of all 139 participants in the evaluable analysis population had at least one adverse event of grade 3 or above by week 24. Among 142 participants who received at least one injection, 43 (30%) experienced at least one injection site reaction (ISR). All 106 ISRs were either grade 1 (98 [92·5%]) or grade 2 (eight [7·5%]), and 97 (91·5%) resolved within 7 days. No participant experienced a drug-related serious adverse event or prematurely discontinued treatment due to a drug-related adverse event.

INTERPRETATION: Long-acting injectable cabotegravir and long-acting injectable rilpivirine, administered to adolescents at recommended adult dosages every 8 weeks, showed no unanticipated safety concerns in the 24 weeks following administration.

FUNDING: National Institutes of Health, ViiV Healthcare, and Johnson & Johnson.

PMID:40049924 | DOI:10.1016/S2352-3018(24)00344-8

J Nucl Med. 2025 Mar 6:jnumed.124.268872. doi: 10.2967/jnumed.124.268872. Online ahead of print.

ABSTRACT

A first-in-human phase I clinical study aimed to assess the safety profile, radiation dosimetry, and biodistribution of a potential cardiac PET myocardial perfusion imaging tracer, [18F]SYN2 (18F-labeled acridine derivative), in healthy subjects. Methods: [18F]SYN2 intravenous administration with PET imaging was performed on healthy volunteers, and sequential whole-body imaging was performed over 4 h. Blood and urine samples were collected for up to 240 min. Safety follow-up visits took place at 2, 5, and 14 d after the administration. Results: Ten subjects (8 women and 2 men) completed all study procedures. The mean age was 38.1 ± 8.8 y, and the mean body mass index was 22.7 ± 3.0 kg/m2 The mean administered dose of radioactivity was 258 MBq (range, 246-272 MBq). There were no drug-related adverse events, and the tracer was well tolerated in all subjects. The mean whole-body effective radiation dose for [18F]SYN2 was 0.0195 mSv/MBq. The tracer was rapidly taken up by the myocardial wall and cleared from plasma, leading to good image quality within minutes of tracer injection. Conclusion: On the basis of the safety profile, radiation dosimetry, and biodistribution of [18F]SYN2, it appears to be a promising agent for clinical PET myocardial perfusion imaging and to warrant further clinical studies.

PMID:40049745 | DOI:10.2967/jnumed.124.268872

Biomaterials. 2025 Mar 3;320:123237. doi: 10.1016/j.biomaterials.2025.123237. Online ahead of print.

ABSTRACT

Acute kidney injury (AKI) is a major cause of mortality in hospitalized patients, yet effective therapeutic interventions remain underdeveloped. To address this critical need, we have employed tetrahedral framework nucleic acid (tFNA) as a carrier to self-assemble a complex incorporating G-quadruplex and hemin (G4/Hemin). This novel formulation exhibits uniform particle size, targeted delivery, and significant therapeutic efficacy for AKI. In a chemotherapy-induced AKI model, G4/Hemin-tFNA preferentially accumulated in the renal tubules, significantly mitigating drug-induced renal tubular injury. In healthy mice, G4/Hemin-tFNA was rapidly cleared from circulation due to efficient renal filtration. Safety evaluations conducted over a continuous 30-day period indicated minimal side effects associated with G4/Hemin-tFNA administration. Mechanistic studies elucidated three primary molecular mechanisms through which G4/Hemin-tFNA exerts its therapeutic effects in AKI: 1) Enhanced Renal Targeting. G4/Hemin-tFNA facilitates effective renal targeting and protection during blood circulation, leading to significant accumulation of drug within the kidneys. 2) Reactive Oxygen Species (ROS) Clearance. The complex exhibits peroxidase-like activity, enabling the rapid clearance of ROS at the site of AKI lesions, thereby inhibiting the oxidative stress progression. 3) Activation of heme oxygenase-1 (HO-1). G4/Hemin-tFNA selectively activates HO-1, enhancing the concentration of anti-inflammatory factors at inflamed sites and promoting an anti-inflammatory microenvironment. Collectively, these findings demonstrate that G4/Hemin-tFNA is a safe and effective therapeutic agent for AKI. By activating HO-1 and clearing ROS, G4/Hemin-tFNA inhibits disease progression, offering a promising approach for the development of future AKI therapies.

PMID:40049024 | DOI:10.1016/j.biomaterials.2025.123237

J Urol. 2025 Mar 6:101097JU0000000000004511. doi: 10.1097/JU.0000000000004511. Online ahead of print.

ABSTRACT

PURPOSE: Adults with low-grade intermediate risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) commonly ask urologists how their routine/responsibilities will be affected by treatments, including the standard of care, transurethral resection of bladder tumor (TURBT). We asked patients in the ENVISION trial (NCT05243550) to compare TURBT to a non-surgical primary treatment (UGN-102 containing mitomycin) for acceptability and impact on their routine/responsibilities.

MATERIALS AND METHODS: ENVISION (NCT05243550) is a phase 3, single arm trial where UGN-102 was administered as six weekly intravesical instillations. Interviews with U.S. patients were conducted at enrollment (before instillations) and 3 months (primary trial endpoint). Transcripts were coded by three coders using the gold standard of content analysis to derive interview themes.

RESULTS: Forty-one U.S. patients from 31 sites were eligible, and 29/41 completed both interviews. Most participants were men (62%), White (83%), and age 65+ (69%). Three themes were derived: 1) Patients perceived that TURBT interfered more with their routine/responsibilities. 2) Urinary symptoms were perceived to be similar, but bleeding, catheter issues, and time to resuming sexual activity lasted longer with TURBT. For UGN-102, uncommon reports were internal itching and difficulty keeping gel in the bladder during instillations. 3) Patients would recommend UGN-102 to other patients because it was perceived to be less invasive, painful, and time-consuming than TURBT.

CONCLUSION: Patients perceived UGN-102 to be a favorable primary treatment alternative to traditional surgical resections for LG-IR-NMIBC. By focusing on the underexplored area of patient perceptions, this study provides key information urologists will need to conduct shared decision-making conversations.

PMID:40048558 | DOI:10.1097/JU.0000000000004511

J Patient Rep Outcomes. 2025 Mar 6;9(1):27. doi: 10.1186/s41687-025-00855-8.

ABSTRACT

BACKGROUND: Monitoring for the side effects of novel therapies using patient-reported outcomes (PROs) is critical for ensuring patient safety. Existing static patient-reported outcome measures may not provide adequate coverage of novel side effects. Item libraries provide a flexible approach to monitoring for side effects using customized item lists, but the ideal process for matching side effects to items sourced from multiple item libraries is yet to be established. We sought to develop a pragmatic process for mapping side effects to items from three major item libraries using immune checkpoint inhibitor (ICI) side effects as an example.

METHODS: Using a consumer- and clinician-driven list of 36 ICI side effects, two authors independently mapped side effects to Common Terminology Criteria for Adverse Event (CTCAE) terms, and then to three item libraries: the Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), the European Organisation for Research and Treatment of Cancer (EORTC) Item Library, and the Functional Assessment of Chronic Illness Therapy (FACIT) searchable library. The rates of inter-rater agreement were recorded. Following item collation from the item libraries, we devised criteria for selecting the optimal item for each side effect for inclusion in a future electronic PRO system based on guidance from the above groups.

RESULTS: All 36 side effects mapped to at least one CTCAE term, with eight mapping to more than one term. Twenty-three side effects mapped to at least one PRO-CTCAE term, 35 side effects mapped to at least one EORTC item, and 31 side effects mapped to at least one FACIT item. The inter-rater agreement rate was 100% (PRO-CTCAE), 83% (EORTC) and 75% (FACIT). Pre-determined criteria were applied to select the optimal item for each side effect from the three item libraries, producing a final 61-item list.

CONCLUSION: Using ICI side effects as an example, we developed a pragmatic approach to creating customized item lists from three major item libraries to monitor for side effects of novel therapies in routine care. This process highlighted the challenges of using item libraries and priorities for future work to improve their usability.

PMID:40048089 | DOI:10.1186/s41687-025-00855-8

Clin Pharmacol Ther. 2025 Apr;117(4):895-909. doi: 10.1002/cpt.3598. Epub 2025 Mar 5.

ABSTRACT

Non-randomized studies will remain the mainstay for evidence on medications' effects in pregnancy since the number of pregnant participants in randomized clinical trials is insufficient to evaluate uncommon but serious pregnancy outcomes. There has been a growing interest in conceptualizing causal inference based on observational data as an attempt to emulate a hypothetical randomized trial: the target trial. This approach can help identify design flaws and ensuing biases and can point toward potential solutions. Adoption of the target trial emulation framework in perinatal studies raises unique challenges due to the distinct role of gestational time. Challenges include, among others, identifying the timing of conception, pregnancy losses as competing events for later outcomes, different etiologically relevant time windows depending on the outcome, and time-varying outcome risks. We discuss various considerations in developing a protocol for a target trial evaluating drug effects in pregnancy and its observational emulation in databases and registries. While not a panacea, the framework offers a valuable tool to guide us through the specification of the causal questions, the study population and the treatment strategies to be compared and helps to identify avoidable biases as well as unavoidable deviations from the optimal protocol. Making these deviations explicit elucidates the assumptions we make when drawing causal conclusions, and the types of analyses that can be undertaken to quantify the potential magnitude of such biases. Such discipline in the design, conduct, and reporting of pregnancy studies will ultimately lead to the best information possible to inform treatment decisions during pregnancy.

PMID:40045450 | DOI:10.1002/cpt.3598

Sci Rep. 2025 Mar 5;15(1):7770. doi: 10.1038/s41598-025-91476-0.

ABSTRACT

This study aims to investigate the adverse effects of immune checkpoint inhibitors (ICIs) on the female and male reproductive systems. In the FDA Adverse Event Reporting System (FAERS) database, adverse reactions under the "Reproductive system and breast disorders" category in the System Organ Classes were included, covering a period from January 1, 2015, to June 30, 2023. We identified 133,512 patients treated with ICIs. Immune checkpoint inhibitor-related reproductive adverse effects (irRAEs) were reported in 568 (0.43%) patients. Spermatogenesis abnormality (ROR025 = 7.91) had the highest signal strength associated with ICI use in males. Genital tract fistula was the only significant irRAE (ROR025 = 2.72) in females. PD-1 inhibitors pose greater risk than CTLA-4 inhibitors (OR = 1.65 [1.05-2.79], p = 0.045). Gynecologic cancers in females (OR = 3.77 [2.82-4.99], p < 0.0001) and urogenital cancers in males (OR = 1.56 [1.17-2.06], p = 0.0018) carried the highest risk compared to other cancers. Additional targeted drugs (OR = 2.32 [1.76-3.02], p < 0.0001), particularly lenvatinib (OR = 3.50 [2.48-4.94], p < 0.0001) and cabozantinib (OR = 3.71 [1.96-7.03], p < 0.0001) significantly increased the risk for females. Additional use of chemotherapy drugs was associated with a significant reduction in the risk for males (OR = 0.65 [0.42-0.96], p = 0.042) except for doxorubicin (OR = 2.58 [1.22-5.47], p = 0.013) and cyclophosphamide (OR = 2.36 [1.05-5.29], p = 0.038). This study demonstrates that ICIs could potentially lead to a wide range of adverse effects in the reproductive system in both males and females.

PMID:40044844 | DOI:10.1038/s41598-025-91476-0

J Neurointerv Surg. 2025 Mar 5:jnis-2025-023068. doi: 10.1136/jnis-2025-023068. Online ahead of print.

ABSTRACT

BACKGROUND: Newly diagnosed glioblastoma (ndGBM) remains one of the most challenging malignancies to treat. Since the majority of patients experience tumor recurrence (rGBM) after first-line therapy, advancements in both initial and salvage treatments are essential.

OBJECTIVE: We report our single-center experience on the feasibility and safety of superselective intra-arterial cerebral infusion (SIACI) with bevacizumab or cetuximab after osmotic blood-brain barrier disruption (oBBBd).

METHODS: Partial results of three distinct trials (anonymized for blinded review) were analyzed. All patients were histopathologically confirmed to have either ndGBM or previously diagnosed ndGBM that progressed to rGBM despite standard therapy and had aKarnofsky Performance Status (KPS)≥70. All patients were admitted on the same day of the surgery, and the intervention followed similar steps in all included patients. Under general anesthesia, after oBBBd with mannitol, patients received SIACI.

RESULTS: Between October 2014 and March 2024, 70 patients with a mean age of 56.2±12.4 years (range: 19-78) underwent successful treatment, encompassing 139 SIACIs and 246 infusions. All planned SIACIs were completed successfully. Forty-one patients with rGBM received bevacizumab-SIACI, 7 with ndGBM bevacizumab-SIACI, and 22 with ndGBM cetuximab-SIACI. In 133 of 139 SIACIs (95.7%), patients were discharged home with a length of stay of 1 day. The incidence of patients who experienced procedure-related and drug-related adverse events was 11.4% and 8.6%, respectively. No procedure-related deaths occurred.

CONCLUSION: In our single-center experience, comprising the largest cohort of bevacizumab or cetuximab SIACI treatment for rGBM and ndGBM, this promising and cutting-edge intervention is highly feasible and safe.

PMID:40044413 | DOI:10.1136/jnis-2025-023068

J Affect Disord. 2025 Mar 3:S0165-0327(25)00345-3. doi: 10.1016/j.jad.2025.03.007. Online ahead of print.

ABSTRACT

This study evaluated adverse events (AEs) associated with Vortioxetine by analyzing extensive data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We collected data from the FAERS database spanning ten years, from the first quarter of 2014 to the second quarter of 2024, focusing on drug-related AEs involving Vortioxetine. A comprehensive analysis was performed using multiple signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Among 13,116 reports where Vortioxetine was identified as the primary suspect drug, AEs were categorized into 27 system organ classes (SOCs) and 146 preferred terms (PTs). The results highlighted significant signals for common AEs, such as psychiatric disorders, gastrointestinal disorders, and nervous system disorders. Notably, feeling guilty exhibited the strongest signal strength; however, its clinical relevance requires cautious interpretation. Additionally, the study identified novel signals not listed in the drug label but potentially of clinical value, such as hyperarousal and alcoholic, which were significantly associated with Vortioxetine. Of particular note, AEs related to sexual dysfunction were the most diverse, while suicidal ideation was the most frequently reported. The study also uncovered rare but noteworthy signals, including hallucination and olfactory disorders, dermatillomania, and bruxism, which warrant further attention. In conclusion, while Vortioxetine demonstrates multifaceted benefits in alleviating symptoms of depression, its clinical use requires a comprehensive evaluation of potential risks. Developing safe and rational treatment strategies is essential to optimize therapeutic outcomes.

PMID:40044085 | DOI:10.1016/j.jad.2025.03.007

BMJ Open Respir Res. 2023 Apr 6;10(1):e001342. doi: 10.1136/bmjresp-2022-001342.

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitors (ICI) have improved outcomes for patients with many malignancies. However, these treatments are associated with immune-related adverse events, including pulmonary toxicity (pneumonitis). Pneumonitis is associated with significant short-term morbidity and mortality, but long-term outcomes are not well described.

METHODS: We used the Vanderbilt Synthetic Derivative, a deidentified electronic health record database of >2.5 million patients seen at Vanderbilt, to identify patient charts that included treatment with pembrolizumab, nivolumab, ipilimumab, ipilimumab and nivolumab, atezolizumab or durvalumab by keyword search and ICD-10 codes for acute respiratory failure and/or bronchoalveolar lavage. We manually reviewed these charts and identified 78 subjects who met criteria for probable pneumonitis which included patients presenting with symptoms (dyspnoea, hypoxia, cough) and/or CT imaging consistent with this diagnosis. We collected data on demographics, ICI regimen, hospital admissions and long-term survival.

RESULTS: Of the 78 patients (48 males; median age 64 (range 28-81)), 52 patients required at least 1 hospital admission related to pneumonitis. A total of 25 patients experienced poor short-term outcomes (including 6 referred to hospice, 11 discharged to rehabilitation and 9 deaths). There was no association with these outcomes by patient age (p=0.96), sex (p=0.60), smoking status (p=0.63) or cancer type (p=0.13). Median duration of follow-up was 8.3 months (range 0.2-110.6 months), and 29 patients (37%) were alive at last follow-up. Patients admitted to the hospital were more likely to die (p=0.002) and less likely to receive additional treatment (p<0.0001) or survive for ≥12 months with no evidence of disease (p=0.02). There were no differences in long-term outcomes for patients with underlying pulmonary comorbidities.

DISCUSSION: ICI-pneumonitis has a high likelihood of causing hospitalisation and poor outcomes, including death. While there appears to be no difference in outcomes for patients with underling pulmonary comorbidities, those requiring admission have worse outcomes.

PMID:40042935 | DOI:10.1136/bmjresp-2022-001342

Front Immunol. 2025 Feb 18;16:1508512. doi: 10.3389/fimmu.2025.1508512. eCollection 2025.

ABSTRACT

OBJECTIVE: To identify predictors of all-grade, grade ≥ 3, and onset time of immune-related adverse events (irAEs) in cancer patients undergoing immune checkpoint inhibitors (ICIs) therapy.

METHODS: This retrospective analysis included cancer patients treated with ICIs at Chongqing Medical University Second Affiliated Hospital from 2018 to 2024. Logistic regression and Cox regression analyses were used to identify predictors of all-grade and grade ≥ 3 irAEs and the time of irAE onset.

RESULTS: Among the 3,795 patients analyzed, 1,101 (29.0%) developed all-grade irAEs, and 175 (4.6%) experienced grade ≥ 3 irAEs. Multivariate logistic regression revealed that female (OR = 1.37, p < 0.001), combination therapy (OR = 1.87, p < 0.001), pre-existing autoimmune diseases (AIDs) (OR = 5.15, p < 0.001), pre-existing cirrhosis (OR = 1.34, p = 0.001), antibiotic use during ICIs treatment (OR = 1.51, p < 0.001), and a higher baseline prognostic nutritional index (PNI) (OR = 1.23, p = 0.01) were significant predictors for the development of all-grade irAEs. The predictors for grade ≥ 3 irAEs included age ≥ 60 (OR = 1.49, p = 0.023) and pre-existing AIDs (OR = 2.09, p = 0.005), For the onset time, predictors included female (HR = 1.26, p = 0.001), combination therapy (HR = 1.80, p < 0.001), pre-existing AIDs (HR = 2.25, p < 0.001), and pre-existing infection (HR = 1.20, p = 0.008).

CONCLUSIONS: Females, combination therapy, pre-existing AIDs and cirrhosis, antibiotics, and a higher baseline PNI are associated with a higher risk of developing all-grade irAEs. Those aged ≥ 60 and with pre-existing AIDs face a higher risk of severe irAEs. Females, undergoing combination therapy, with pre-existing AIDs and infection generally experience a shorter time to irAEs onset. Multicentric prospective studies are warranted to validate these findings.

PMID:40040713 | PMC:PMC11876122 | DOI:10.3389/fimmu.2025.1508512

BMC Geriatr. 2025 Mar 4;25(1):144. doi: 10.1186/s12877-025-05732-z.

ABSTRACT

BACKGROUND: Older adults are vulnerable to adverse drug events given the pharmacokinetic and pharmacodynamic changes that coming with ageing, as well as they often take multiple medications for their chronic health conditions, especially older co-morbidities. ADEs can cause unnecessary emergency department visits and hospitalization, which contribute to financial burden and decreased quality of life. This study aims to investigate the prevalence of adverse drug events in elderly co-morbid patients in Liaoning province and explore its risk factors, in order to ensure medication safety in elderly patients.

METHODS: This was a cross-sectional study that enrolled elderly patients with co-morbidities, and the data were collected by nurses using a structured interview method for elderly patients with multimorbidity. Risk factors for patient-reported adverse drug events were identified by univariate and logistic regression analyses.

RESULTS: A total of 329 elderly patients were enrolled, among whom 169 were females, with an age ranging from 61 to 90 years. 205 participants (62.3%) had 462 "possible-probable-certain" adverse drug events, and 156 (47.4%) experienced two or more self-reported adverse drug events concurrently. The logistic regression analysis included four variables: female (OR = 2.194, 95% confidence interval 1.281-3.760, P = 0.004), numbers of daily drugs > 12 (OR = 2.257, 95% confidence interval 1.254-4.061, P = 0.007), history of fall within 1 year (OR = 3.106, 95% confidence interval 1.112-8.674, P = 0.031), and medication noncompliance (OR = 3.768, 95% confidence interval 1.535-9.249, P = 0.004).

CONCLUSION: Patient-reported adverse drug events are more prevalent in older co-morbid patients in Liaoning province. Female, numbers of daily drugs, fall history with 1 year and poor medication compliance were significantly and independently associated with adverse drug events. These findings may provide informative interventions for the medication management in elderly patients living with multimorbidity.

PMID:40038590 | DOI:10.1186/s12877-025-05732-z

Int J Psychiatry Med. 2025 Mar 4:912174251326009. doi: 10.1177/00912174251326009. Online ahead of print.

ABSTRACT

BACKGROUND: Depression is prevalent among individuals with chronic kidney disease (CKD) and those undergoing dialysis, with significant impacts on morbidity and mortality. This systematic review and meta-analysis was done to evaluate the efficacy of psychosocial interventions in managing depressive symptoms in patients with CKD.

METHODS: This systematic review and meta-analysis adhered to PRISMA guidelines. A literature search was conducted across PubMed, Embase, Google Scholar, and Cochrane Library databases from January 2007 to July 2024. Randomized controlled trials (RCTs) investigating psychosocial interventions in CKD patients (Stage 4 or 5 or on hemodialysis) were included. The primary outcome was the change in depressive symptoms, measured by standardized clinical tools. Quality of life was a secondary outcome. Data extraction and bias assessment were conducted using ROB-2 and GRADEpro GDT tools.

RESULTS: Twelve studies with a total of 792 participants (420 in the intervention group and 372 in the control group) were included. Cognitive-behavioral therapy (CBT) was the most common intervention. Psychosocial interventions significantly reduced depressive symptoms compared to routine care (mean difference [MD]: -4.22; 95% CI: -6.67, -1.76; P = 0.0008). High heterogeneity (I2 = 89%) was noted. Sensitivity analysis confirmed the robustness of the results. The impact on quality of life was not statistically significant (MD: 0.94; 95% CI: -0.61, 2.49; P = 0.24).

CONCLUSIONS: Moderate-quality evidence suggests that psychosocial interventions effectively reduce depressive symptoms in CKD patients. While no significant improvement in quality of life was observed, these interventions provide an alternative to pharmacological treatments, potentially minimizing drug-related side effects.

PMID:40037371 | DOI:10.1177/00912174251326009

Expert Opin Drug Saf. 2024 Dec 30:1-5. doi: 10.1080/14740338.2024.2448830. Online ahead of print.

ABSTRACT

BACKGROUND: Antineoplastic drug-associated adverse cardiovascular events (ACEs) are a concern; however, information on new antineoplastic drugs is limited. In this situation, signal detection and hypothesis building by analyzing the pharmacovigilance database are useful. However, increased numbers of reports on COVID-19 vaccine-related ACEs in the pharmacovigilance database have affected the results of the disproportionality analysis. Therefore, examining the effect of increased reports on COVID-19 vaccine-related ACEs on detecting anticancer drug-related ACEs is critical.

RESEARCH DESIGN AND METHODS: Disproportionality analysis was performed using the Japanese Adverse Drug Event Report (JADER) database. Reporting odds ratio and information components were used as indicators to detect potential associations between drugs and adverse events. The analysis was performed in two situations: using all data in the JADER database and excluding cases with the COVID-19 vaccine.

RESULTS: Various antineoplastic drugs were associated with diverse ACEs. Additionally, safety signals for ACEs of some antineoplastic drugs were masked by reports on COVID-19 vaccine-related ACEs.

CONCLUSIONS: The rapid increased reports on COVID-19 vaccine-related ACEs in the JADER database had an impact on signal detection activities for antineoplastic drug-associated ACEs. Therefore, the impact of reporting COVID-19 vaccine-related ACEs on current signal detection activities should be evaluated over time.

PMID:40035831 | DOI:10.1080/14740338.2024.2448830

Ceska Slov Farm. 2025;73(2):93-102. doi: 10.36290/csf.2024.015.

ABSTRACT

Drug-related hospitalizations - insights from the Czech Republic Background and objective: Drug-related hospitalizations represent a significant burden on healthcare. The aim of the study was to determine the prevalence of drug-related hospitalizations and identify medications and clinical manifestations associated with drug-related hospitalizations in patients admitted to hospital through the emergency department.

METHODS: This cross-sectional study examined unplanned hospitalizations at the University Hospital Hradec Kralove through the Department of Emergency Medicine between August and November 2018. Data were obtained from electronic health records. The methodology for identifying drug-related hospitalizations was based on the guideline of the European project OPERAM. This article focuses on a subgroup of drug-related problems related to the medication safety.

RESULTS: Of the total 1252 hospitalizations analyzed, 145 cases were identified as drug-related. The prevalence of drug-related hospitalizations was 12% (95% confidence interval 10-13). In 62% of cases, medications only contributed to the cause of hospitalization. Antithrombotics, cytostatics, diuretics, and systemic corticosteroids were the most common medication classes leading to drug-related hospitalizations. Gastrointestinal bleeding was the most common cause of drug-related hospitalizations. The potential preventability of drug-related hospitalizations was 34%.

CONCLUSION: Drug-related hospitalizations remain relatively common, while some of them could be potentially prevented. Pharmacists can contribute to enhancing patient safety by detecting drug-related problems and proposing measures to minimize risks.

PMID:40035300 | DOI:10.36290/csf.2024.015

World J Mens Health. 2025 Feb 27. doi: 10.5534/wjmh.240295. Online ahead of print.

ABSTRACT

PURPOSE: Pentosan polysulfate sodium (PPS) is the only pharmacological intervention approved by the US Food and Drug Administration for treating interstitial cystitis (IC) to date. However, PPS may induce an adverse event, maculopathy, which can be a significant challenge. To determine the risk of PPS-induced maculopathy in patients with IC.

MATERIALS AND METHODS: PubMed and Embase were systematically searched through July 2024. Two authors also independently and manually searched all relevant studies. We included national level cohort studies using healthcare claim big data or real-world data with the following criteria: (1) patients diagnosed with IC; (2) interventions included PPS as an active treatment; (3) comparisons were specified as non-PPS interventions; and (4) the primary outcome of interest was the risk of maculopathy. The pairwise meta-analysis was performed to compare the PPS treatment group with control used in IC. The primary outcome measure was the hazard ratio (HR), odds ratio (OR), and proportional report ratio (PRR) of maculopathy after receiving the PPS treatment, as compared to non-PPS interventions.

RESULTS: A comprehensive literature search was conducted, and identified 6 studies with 411,098 patients. The pooled risk for maculopathy due to PPS in patients with IC was significant (HR, 1.678; 95% confidence interval [95% CI], 1.066-2.642]). The heterogeneity test produced a Higgins' I-squared statistic, which was 83.6%. In the subgroup analysis of follow-up period of less than 5 years (HR, 1.285; 95% CI, 1.139-1.449) and more (HR, 1.341; 95% CI, 1.307-1.375) were statistically significant, indicating that the patients with IC who had a long-term PPS treatment were more likely to have maculopathy than the control groups.

CONCLUSIONS: This is the first study to investigate the relationship between PPS and its association with the risk of maculopathy in patients with IC through a systematic review and meta-analysis.

PMID:40034025 | DOI:10.5534/wjmh.240295

IEEE J Biomed Health Inform. 2025 Mar;29(3):1759-1770. doi: 10.1109/JBHI.2024.3510297. Epub 2025 Mar 6.

ABSTRACT

Investigating the inhibitory effects of compounds on cardiac ion channels is essential for assessing cardiac drug safety. Consequently, researchers have developed computational models to evaluate combined cardiotoxicity (CCT) on cardiac ion channels. However, limitations in experimental data often cause issues like uneven data distribution and scarcity. Additionally, existing models primarily emphasize atomic information flow within graph neural networks (GNNs) while overlooking chemical bonds, leading to inadequate recognition of key structures. Therefore, this study integrates optimal transport (OT), structure remapping (SR), and Kolmogorov-Arnold networks (KANs) into a GNN-based CCT prediction model, CardiOT. First, the proposed CardiOT model employs OT pooling to optimize sample-feature joint distribution using expectation maximization, identifying "important" sample-feature pairs. Additionally, SR technology is used to emphasize the role of chemical bond information in message propagation. KAN technology is integrated to greatly enhance model interpretability. In summary, the model mitigates challenges related to uneven data distribution and scarcity. Multiple experiments on public datasets confirm the model's robust performance. We anticipate that this model will provide deeper insights into compound inhibition mechanisms on cardiac ion channels and reduce toxicity risks.

PMID:40030556 | DOI:10.1109/JBHI.2024.3510297

Malar J. 2025 Mar 3;24(1):71. doi: 10.1186/s12936-025-05295-9.

ABSTRACT

BACKGROUND: Active surveillance involves systematically monitoring patients to seek detailed information about the occurrence of adverse events (AEs) following drug administration. The Seta technology was developed to improve active surveillance of AEs or pregnancy in low- and middle-income countries and geographically challenging areas. Seta actively solicits responses from participants via WhatsApp messages. The study aimed to determine whether Seta facilitated reporting of AEs and pregnancies to the Brazilian National Health Surveillance Agency (ANVISA).

METHODS: Malaria patients participating in the Tafenoquine Roll-out STudy (TRuST) in Brazil's Amazon region were invited to participate in this observational pilot study evaluating Seta. The study was conducted at two sites from 27 July 2022 to 28 October 2022. Seta sent messages to all participants on Day 7 and in Week 8 asking if they had experienced an AE or if they had become pregnant during the time since they took the malaria medication. If a participant responded "yes", a pharmacovigilance coordinator (PVC) called them to collect further details, which the PVC was then encouraged to report to ANVISA.

RESULTS: This pilot study included 149 participants, 50 from Manaus and 99 from Porto Velho. On Day 7, 117 (79%) of 149 participants responded to WhatsApp messages generated by Seta asking whether they had experienced an AE or become pregnant; 45 participants responded "yes". At Week 8, 64 (55%) of the Day 7 responders also responded, 10 of whom indicated that they had experienced an AE or become pregnant. A total of 55 follow-up calls were therefore attempted by PVCs, of which, 25 (45%) were answered and allowed for reporting of AEs and pregnancies, as appropriate, to ANVISA.

CONCLUSIONS: This observational pilot study provides insights into how digital reporting tools such as Seta can enhance pharmacovigilance in remote areas and build upon existing signal detection methodologies. Twenty-five AEs or pregnancies were reported to ANVISA that were unlikely to have been reported otherwise.

PMID:40033382 | DOI:10.1186/s12936-025-05295-9

Sci Rep. 2025 Mar 3;15(1):7411. doi: 10.1038/s41598-025-91753-y.

ABSTRACT

Individuals with latent tuberculosis infection (LTBI) are at risk of progressing to active tuberculosis (TB), which remains a significant cause of death globally. Although various antiTB medications-rifampin and isoniazid-exist for treating for both LTBI and active TB, pharmacovigilance studies evaluating their adverse effects are especially scare for LTBI. Given the continued status of South Korea as having the highest TB incidence among Organization for Economic Cooperation and Development countries, this study examines drug-related adverse events (AEs) and identifies novel signals associated with rifampin or isoniazid in TB prevention and treatment in South Korea using the national AE reporting system. Analyzing data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KAERS DB, 2301A0006) between 2017 and 2021, we observed that rifampin was frequently listed as a suspected drug in AE reports. Serious adverse events (SAEs), including life-threatening events and hospitalizations, were observed in LTBI as well as active TB cases when rifampin was the suspected drug. Novel signals, including QT prolongation and acne, were also identified, underscoring the importance of AE monitoring in LTBI or active TB treatment.

PMID:40032948 | DOI:10.1038/s41598-025-91753-y