Nevin Manimala

Drug Saf. 2025 Dec 6. doi: 10.1007/s40264-025-01632-8. Online ahead of print.

ABSTRACT

BACKGROUND: Databases for safety monitoring of medicinal products contain records of a huge number of pairings of drugs and adverse events (AEs). Existing disproportionality methods for safety monitoring in such databases estimate background rates of AE occurrence in ways that may be susceptible to masking effects that can hinder signal detection, particularly in the context of large overall counts of AE or drug occurrence in the data.

OBJECTIVES: To develop a new statistical model for determining the background rate against which individual drug-AE pairs are to be evaluated, which is robust against masking effects, and to incorporate this into an algorithm which simultaneously estimates background rates and detects drug-AE pair counts that deviate significantly from these rates.

METHODS: We constructed a hierarchical Bayesian model for background rates, and background rate samples were drawn from the model parameters using an iterative Markov Chain Monte Carlo (MCMC) method. At each iteration, any counts whose probability is low given current background rate estimation were removed from the computation that sampled the next set of background rates. The algorithm, called Markov Chain Signal Generation (MCSG), was implemented using a combination of Python and the probabilistic programming language Stan.

RESULTS: The MCSG algorithm outperformed routinely used quantitative approaches for signal detection on both synthetic data designed to include a drug-AE pair with very strong masking effects and a reference set featuring 69 unique active substances and 792 unique AEs. On a synthetic dataset where selected pairs occurred at rates deviating from a constant background, MCSG accurately identified these pairs in the presence of strong masking signals. On a subset of some real data from the FDA Adverse Event Report System (FAERS), it effectively identified a reference set of positive and negative controls and was able to identify drug-AE pairs suggested in the literature.

CONCLUSION: We have demonstrated a new approach to signal generation, which avoids the confounding effect of masking more effectively than currently used methods. The algorithm is best used in a setting of multiple drug-AE pairs, the majority of which are expected to have counts at background rate, although with substantial datasets the algorithm can take minutes or hours to run. It is therefore particularly suitable for infrequent, large-scale analysis (for example, quarterly analysis of the entirety of a pharmacovigilance database).

PMID:41351764 | DOI:10.1007/s40264-025-01632-8

J Interv Card Electrophysiol. 2025 Dec 6. doi: 10.1007/s10840-025-02190-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Cardiovascular disease is one of the leading causes of death in patients with type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have proven to be beneficial in improving cardiovascular outcomes and reducing all-cause mortality in patients with T2DM. We aimed to investigate the effect SGLT2i use on cardiovascular outcomes inpatients with T2DM who underwent VT ablation.

METHODS: A retrospective cohort study was conducted using the TriNetX US Collaborative Network, a federated network of healthcare organizations across the United States. Adults (aged 18-80 years) with T2DM who underwent catheter ablation for ventricular tachycardia were included. Patients were stratified based on exposure to SGLT2i. Propensity score matching (1:1) was used to balance baseline characteristics. Outcomes were assessed within 3 years following the index ablation procedure. Patients with a recorded occurrence of the outcome prior to the index event were excluded from each respective outcome analysis. Kaplan-Meier analysis and log-rank tests were used for statistical comparisons with significance set at p < 0.05.

RESULTS: SGLT2 inhibitor non-users exhibited significantly higher hazard ratios (HR) for various adverse outcomes. The HR for all-cause mortality was 1.422 (95% CI: 1.279-1.581), while the HR for cardiac arrest was 1.409 (95% CI: 1.135-1.750). Additionally, the HR for post-ablation cardioversion was 1.188 (95% CI: 1.042-1.355), and the utilization of amiodarone after ablation had an HR of 1.240 (95% CI: 1.106-1.391). In contrast, the hazard ratios for redo ablation (1.039, 95% CI: 0.956-1.128), visits for ICD adjustments (0.916, 95% CI: 0.766-1.096), post-ablation use of any class of antiarrhythmics (1.139, 95% CI: 0.906-1.431), and lidocaine (0.911, 95% CI: 0.775-1.070) were less definitive.

CONCLUSION: SGLT2i non-user group was associated with significantly higher risks of several adverse outcomes following ablation, including a 42% increase in all-cause mortality and a 41% increase in cardiac arrest. Non-users also had higher rates of post-ablation cardioversion and amiodarone use. However, no significant differences were found in redo ablation, ICD adjustments, or the use of other antiarrhythmics. These findings suggest a potential protective role of SGLT2 inhibitors in selective cardiovascular outcomes. Further studies are warranted to confirm these associations and investigate the underlying mechanisms.

PMID:41351762 | DOI:10.1007/s10840-025-02190-w

J Occup Rehabil. 2025 Dec 6. doi: 10.1007/s10926-025-10349-5. Online ahead of print.

ABSTRACT

PURPOSE: To compare employment status 5 years post-diagnosis among native Norwegian, Western immigrant, and non-Western immigrant female cancer survivors (CSs) and their matched controls without cancer, who were employed at the time of diagnosis.

METHODS: Participants were categorized into three groups based on data from Statistics Norway: Natives (CSs = 6587, control = 6587), Western immigrants (CSs = 209, control = 209), and non-Western immigrants (CSs = 105, control = 105). Women were aged 30-55 at diagnosis, employed (salaried/self-employed) at baseline, and alive at 5-year follow-up. CSs and controls were matched on age, education, and employment at diagnosis. Associations between cancer status, immigrant background, and employment were analyzed using binary logistic regressions and Firth penalized logistic regression to account for potential bias from small subgroup sizes.

RESULTS: At 5 years, female CSs had lower odds of employment compared with controls. Western immigrants did not differ from natives, whereas non-Western immigrants showed reduced employment. Higher income was positively associated with employment, while being married or cohabiting and working in the public sector were linked to higher odds. Interaction terms between cancer survivorship and immigrant background were not significant.

CONCLUSION: Among women employed at baseline, cancer survivorship and non-Western immigrant background were independently associated with lower odds of employment five years later. Tailored employment support is needed for non-Western immigrants to improve long-term outcomes. Interventions should also target employers and workplaces to support employment maintenance among CSs.

PMID:41351748 | DOI:10.1007/s10926-025-10349-5

J Robot Surg. 2025 Dec 6;20(1):57. doi: 10.1007/s11701-025-03011-y.

ABSTRACT

As robotic-assisted total knee arthroplasty (TKA) continues to evolve, a key clinical question is whether the learning curve and clinical outcomes differ between CT-dependent and image-independent robotic systems. This retrospective study compared the learning curves and early clinical outcomes of 101 patients undergoing TKA with either a CT-dependent robotic system (Beijing HURWA, Group A) or an image-independent system (Smith & Nephew CORI, Group B). A statistically significant intergroup disparity (P < 0.05) was noted in the rates of transition to conventional treatment, with Group A exhibiting a higher frequency during the learning phase. However, this phase did not witness a significant difference between the groups for other outcomes (p > 0.05). Cumulative sum (CUSUM) analysis was employed to chart the learning curve., peaked at the 15th case for Group A and the 14th for Group B, indicating a similar number of cases to achieve proficiency. During both learning and proficiency phases, the HURWA system demonstrated a shorter bone resection time but longer reference array mounting and registration times. Radiographically, the CT-dependent HURWA system showed superior performance in achieving optimal frontal and lateral femoral component (FFC, LFC) angles. In the early learning phase, Group A reported higher pain scores (VAS) at postoperative day 7, but this difference resolved by day 180. A comparison of the groups demonstrated comparable final knee function (KSS, ROM) and complication rates at all assessment points. The findings indicate that while the two robotic systems exhibit distinct operational time profiles and early radiographic advantages for the CT-dependent system in femoral positioning, both facilitate comparable and satisfactory early clinical outcomes after the initial learning period.

PMID:41351741 | DOI:10.1007/s11701-025-03011-y

Geroscience. 2025 Dec 6. doi: 10.1007/s11357-025-02008-7. Online ahead of print.

ABSTRACT

The rising prevalence of cognitive disorders highlights the urgent need for effective prevention strategies and therapeutic interventions. While adherence to a balanced diet has been associated with a reduced risk of cognitive decline, emerging evidence underscores the potential role of plant-derived bioactive compounds, such as (poly)phenols, with anthocyanins receiving increasing attention. This meta-analysis aimed to evaluate the effect of anthocyanin-rich interventions on cognitive performance. A systematic search of randomized controlled trials (RCTs) assessing the effects of anthocyanin supplementation and cognitive outcomes identified 59 eligible studies. Overall, anthocyanin intervention significantly improved global cognition (standardized mean difference (SMD) = 0.46, 95% CI = 0.30 to 0.63, I² = 0.0%) compared with controls. Domain-specific analyses further revealed significant benefits for visuospatial processing/reasoning and attention (SMD = 0.37, 95% CI = 0.18 to 0.55, I² = 76.3%), processing and psychomotor speed (SMD = 0.19, 95% CI = 0.05 to 0.34, I² = 64.0%), verbal speed and fluency (SMD = 0.21, 95% CI = 0.03 to 0.39, I² = 30.5%), episodic memory (SMD = 0.30, 95% CI = 0.10 to 0.50, I² = 75.9%), and working memory (SMD = 0.24, 95% CI = 0.12 to 0.36, I² = 46.5%). Collectively, these findings suggest that anthocyanin supplementation may improve multiple cognitive domains. Although these results are promising, further well-designed RCTs are needed to validate these outcomes and consolidate the current evidence base.

PMID:41351717 | DOI:10.1007/s11357-025-02008-7

Eur J Orthop Surg Traumatol. 2025 Dec 6;36(1):37. doi: 10.1007/s00590-025-04604-x.

ABSTRACT

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have recently garnered increased attention due to their effectiveness in inducing marked weight loss among overweight and obese adults. Recent evidence, however, has raised concerns about a potential link between GLP-1 receptor agonist therapy and perioperative pulmonary aspiration. In this single-institution retrospective series, we aimed to quantify the incidence of intraoperative and early postoperative complications among patients taking GLP-1 RA before elective total joint arthroplasty (TJA).

METHODS: All patients who underwent primary TJA at our institution between April 2014 and October 2023 were initially screened. Patients were considered eligible for inclusion if they demonstrated consistent preoperative GLP-1 RA utilization. GLP-1 RA medication type, dosage, administration method, and treatment duration were tabulated for each patient. The primary outcomes of interest wereintraoperative anesthesia-related complications, particularly pulmonary aspiration, postoperative medical and surgical complications, and 90-day reoperation.

RESULTS: In total, 83 patients demonstrated consistent GLP-1 RA usage before primary TJA. Of these patients, 63 (75.9%) received semaglutide, 19 (22.9%) liraglutide, and 1 (1.2%) tirzepatide. No cases of acute intraoperative pulmonary aspiration were identified. Intraoperative assessment of gastric contents was not routinely performed; however, one patient was noted to have a full stomach requiring nasogastric decompression. This individual was in the dose-escalation phase of treatment, having self-administered 1 mg of semaglutide five days before surgery. Four patients (4.8%) experienced 90-day medical complications, none of which were attributed to GLP-1 RA use, and one patient (1.2%) required reoperation.

CONCLUSION: Despite recent studies suggesting an elevated risk of acute intraoperative pulmonary aspiration, our findings underscore the rare nature of intraoperative anesthesia-related adverse events in TJA patients taking GLP-1 RA.

PMID:41351714 | DOI:10.1007/s00590-025-04604-x

Mol Neurobiol. 2025 Dec 6;63(1):264. doi: 10.1007/s12035-025-05434-y.

ABSTRACT

Depression, a common psychiatric condition, is frequently associated with chronic stress. This research investigates the therapeutic benefit of chamomile (Matricaria chamomilla) against restraint stress (RS)-induced behavioral and neurobiological alterations in male mice. Animals were categorized into control, RS, and RS + chamomile (Cm) groups. Behavioral evaluation (open field, rotarod, catalepsy, memory test), histopathology, integrity of the blood-brain barrier, and gene expression profiling were done. In silico ProTox analysis confirmed the non-toxicity of chamomile compounds, including chamazulene, which also complies with Lipinski’s Rule of Five, indicating drug-like properties. Molecular docking identified robust interactions between chamazulene and prominent stress-related and other relevant targets like IFN-γ, IL-6, caspase-3, BDNF, and GLUT-1. RS exposure interfered with locomotor activity, evoked neuroinflammation, apoptosis, and compromised neuronal-glial function. Treatment with chamomile greatly enhanced locomotor function and posture, decreased catalepsy latency test, and normalized neuronal architecture. Immunofluorescence staining and transcriptional analysis indicated that chamomile suppressed pro-inflammatory cytokines (IFN-γ, IL-6), the apoptotic marker Caspase-3, and increased neurotrophic and neuronal markers (BDNF, NeuN, GFAP) and glycolytic enzymes (GLUT-1, HK-1, LDHA). These results indicate that chamomile has neuroprotective actions by regulating RS-induced inflammation, apoptosis, and metabolic dysfunction. Although no remarkable effects were seen on body or brain-to-body weight ratio, chamomile exhibited powerful behavioral and molecular effects. Overall, the results highlight chamomile, particularly its active constituent chamazulene, as a promising candidate for alleviating restraint stress. However, further clinical validation is required to establish its therapeutic potential in neuropsychiatric disorders.

PMID:41351710 | DOI:10.1007/s12035-025-05434-y

Eur Radiol. 2025 Dec 6. doi: 10.1007/s00330-025-12185-w. Online ahead of print.

ABSTRACT

OBJECTIVES: To address Croatia’s high lung cancer mortality and late-stage diagnoses, the Ministry of Health initiated a multidisciplinary effort to design a national lung cancer screening program.

MATERIALS AND METHODS: Lung cancer remains one of the leading causes of cancer-related mortality both globally and in Croatia. In 2021 alone, Croatia recorded over 3300 new cases of lung cancer and more than 2800 associated deaths, indicating a high mortality burden. In response to this public health concern, the Ministry of Health has established a multidisciplinary Lung Cancer Screening Working Group, tasked with developing a national screening approach. The Program incorporates several innovative elements, including the application of modified International Early Lung Cancer Action Program (I-ELCAP) criteria for nodule management, volumetric analysis assessed by artificial intelligence, complete digitalization, smoking cessation, and nationwide deployment to ensure equitable access.

RESULTS: From October 2020 to August 2025, over 50,000 participants were screened, resulting in more than 70,000 LDCT scans performed. The cohort includes 54% male and 46% female participants, with an average age of 62 years. Among these participants, 4.5% had positive results, which required further follow-up.

CONCLUSION: The Croatian National Lung Cancer Screening Program offers unique features as it has been comprehensively incorporated into the existing healthcare infrastructure and is fully reimbursed. A key aspect of the program is the important role assigned to general practitioners (GPs), who are responsible for identifying and referring individuals at high risk for lung cancer.

KEY POINTS: Question No European Union country has implemented a national lung cancer screening program despite evidence from previous trials showing significant mortality reduction. Findings Croatia successfully launched a fully integrated national lung cancer screening program using LDCT, AI-assisted volumetric analysis, modified I-ELCAP criteria, and GP-centered recruitment. Clinical relevance The Croatian model demonstrates the feasibility of national lung cancer screening within a European public healthcare system with full reimbursement, providing a replicable framework for other EU countries implementing lung cancer screening programs.

PMID:41351704 | DOI:10.1007/s00330-025-12185-w

Environ Monit Assess. 2025 Dec 6;198(1):16. doi: 10.1007/s10661-025-14867-w.

ABSTRACT

Urban forests play a vital role in sustainable cities by providing ecological, social, and climatic benefits. However, tree selection often emphasizes aesthetics and pollution control, overlooking resilience to extreme weather, particularly cyclones in coastal regions. This study proposes a climate-resilient tree selection framework that integrates ecological function and mechanical stability. Thirty-four commonly planted species in Bhubaneswar, a cyclone-prone city in Odisha, India, were evaluated using four indices: Air Pollution Tolerance Index (APTI), Cyclone Tolerance Index (CTI), Use Value Index (UVI), and Morphometric Character Index (MCI). APTI was derived from leaf physio-biochemical traits; CTI from cyclone damage reports and UVI and MCI from ethnobotanical surveys and morphological data. These indices were normalized and combined into an Integrated Resilience and Utility Index (IRUI) to rank species suitability for urban planting. Based on IRUI values, species were categorized into five suitability classes ranging from very high to unsuitable. Azadirachta indica was identified as very highly suitable, while eleven species including Mimusops elengi, Neolamarckia cadamba, Alstonia scholaris, and Ficus religiosa were highly suitable for cyclone-prone polluted urban environments. Regression analysis indicated positive contributions of all four indices to IRUI, ranked as CRI > APTI > MCI > UVI. This framework provides a data-driven basis for urban planners to design multifunctional, climate-resilient green spaces, supporting Sustainable Development Goal 11 (Sustainable Cities and Communities).

PMID:41351643 | DOI:10.1007/s10661-025-14867-w

Environ Monit Assess. 2025 Dec 6;198(1):15. doi: 10.1007/s10661-025-14833-6.

ABSTRACT

The Monterrey Metropolitan Area (MMA) in Northeastern Mexico, already burdened by significant industrial pollution, experienced a severe drought crisis during the 2020-2023 triple-dip La Niña. This prolonged climate anomaly triggered three major fire episodes in the Sierra Madre Oriental (SMO), sharply increasing particulate matter (PM10 and PM2.5) concentrations. To assess the impact of wildfire emissions on urban pollution, this study integrates ground-based air quality and meteorological measurements, satellite-derived data (VIIRS fire radiative power and MODIS aerosol optical depth), drought indicators from the North American Drought Monitor (NADM), and dispersion modeling using Nonparametric Wind Regression (NWR). Fire-attributable contributions increased by up to 53.3 $\mu$ gm $_{}^{–3}$ for PM10 and 12.8 $\mu$ gm $_{}^{–3}$ for PM2.5, frequently exceeding both Mexican and WHO air quality standards. On average, the three wildfires accounted for relative increases of 110% in PM10 and 49% in PM2.5 compared to non-fire conditions. These increases were linked to wind-driven smoke transport from the SMO to the MMA, demonstrating that three megafires substantially degraded urban air quality during a period of extreme drought. As climate change is expected to increase the frequency of multi-year ENSO episodes, thereby prolonging droughts and intensifying wildfire occurrence, our findings underscore the urgent need to incorporate biomass burning aerosol emissions into air quality management strategies and health impact assessments in other regions experiencing similar conditions.

PMID:41351638 | DOI:10.1007/s10661-025-14833-6