Category: Nevin Manimala

Eur J Drug Metab Pharmacokinet. 2025 Jul 31. doi: 10.1007/s13318-025-00959-y. Online ahead of print.

ABSTRACT

INTRODUCTION: An increasing number of patients in clinical practice are transitioning from intravenous (IV) to subcutaneous (SC) dosing of infliximab. In this simulation study, we evaluated hypothetical dosing scenarios both for typical adults and adults with obesity and for children switching from steady-state IV to SC infliximab, as well as those initiating SC infliximab therapy.

METHODS: By combining two previous published infliximab models, we were able to simulate both IV and SC dosing in adults and children. Various dosing regimens were simulated using a large virtual population. In each scenario, the distribution of trough concentrations and area under the plasma concentration-time curve (AUC) was calculated.

RESULTS: Peak levels were higher after IV dosing compared with SC dosing, while trough levels were higher after SC dosing, leading to more stable infliximab levels over time. Overall exposure remained largely similar when switching from a standard IV to SC dosing regimen. Patients with a high body mass index and those on high-frequency IV dosing regimens of infliximab demonstrated reduced exposure when transitioned to the fixed SC dose. Paediatric patients exhibited higher exposure on the fixed SC dose. Simulation of SC induction schemes demonstrated early achievement of steady-state plasma levels.

CONCLUSION: Infliximab exposure (AUC) remains largely similar when transitioning from standard IV to SC dosing. Current dosing regimens may not be optimal for patients with severe obesity, paediatric patients and patients on high-frequency infliximab regimens. These findings provide a foundation for future clinical research to refine SC infliximab dosing in these populations.

PMID:40742528 | DOI:10.1007/s13318-025-00959-y

Macromol Rapid Commun. 2025 Jul 31:e00251. doi: 10.1002/marc.202500251. Online ahead of print.

ABSTRACT

This study aimed to identify solvent characteristics that enhance drug loading in polymeric micelles. Polyethylene glycol-block-polystyrene (PEG-b-PS) and curcumin were used as model compounds to investigate the impact of 40 different solvent mixtures on drug loading during flow-based assembly. We tested five algorithms: Random Forest (RF), Gradient Boosting (GP), XGBoost, Support Vector Regression (SVR), and Multilayer Perceptron (MLP), with the MLP model proving to be the most effective among them. To explain the model’s predictions, we utilized SHapley Additive exPlanations (SHAP) values to identify solvent properties that contribute to high drug loading. Of the nine descriptors examined-curcumin solubility, polarity, Hildebrand solubility parameters, dipole moment, dielectric constants, viscosity, and Hansen solubility parameters (δD, δP, and δH)-solubility emerged as the most critical factor. Therefore, to achieve optimal drug loading, researchers should prioritize solvents with the highest solubility.

PMID:40742525 | DOI:10.1002/marc.202500251

Mol Diagn Ther. 2025 Jul 31. doi: 10.1007/s40291-025-00801-w. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Primary ciliary dyskinesia (PCD) is a rare genetic condition characterised by abnormal ciliary motility, primarily affecting the respiratory tract. Despite its clinical significance, there is currently no gold standard for PCD diagnosis. This study aims to address this diagnostic challenge by evaluating a comprehensive approach in a large cohort of patients with suspected PCD.

METHODS: We conducted a retrospective analysis of 128 patients with suspected PCD at a specialised clinical reference unit. A thorough anamnesis was performed, followed by a triad of diagnostic tests: (i) a high-speed video analysis of ciliary beat pattern; (ii) transmission electron microscopy for ciliary ultrastructure examination; and (iii) a genetic analysis, primarily through clinical exome sequencing. Correlations between the clinical, morphological and genetic findings were studied. Functional assays on RNA were performed to assess new splicing variants. Pearson’s chi-square test was used to compare categorical variables and comparisons of means were performed using the Student’s t-test.

RESULTS: A definitive PCD diagnosis was established in 72% of the studied patients. Notably, only 58% of the diagnosed cases showed positive results across all three diagnostic tests. Patients with immotile cilia have a higher frequency of neonatal respiratory distress and had a higher likelihood of receiving a genetic diagnosis. A high-speed video analysis was altered in 116 patients, 53 of them with immotile cilia. A transmission electron microscopy revealed ultrastructural alterations in 67 patients, with class 1 defects being more common. DNAH5, RSPH1 and DNAH11 were the most represented genes among the 18 causal genes found. Among the 71 causal genetic variants found, we highlight the overrepresentation of the c.85G>T in RSPH1 and describe the aberrant effect on RNA of the splicing variants DNAH11:c.11497-6T>G, DNAH9:c.2596-2dup, CCDC40:c.2597A>G and CCDC40:c.2832G>A. Finally, we describe a severe phenotype associated with the RSPH1 gene, contrary to previously reported data.

CONCLUSIONS: This comprehensive analysis of a large cohort of patients with PCD underscores the challenges in achieving a definitive diagnosis and emphasises the need for a multi-faceted diagnostic approach. This study enhances our understanding of this rare condition, including the identification of new splicing variants and an unexpected severe phenotype associated with RSPH1, challenging previous assumptions about genotype-phenotype correlations in PCD.

PMID:40742517 | DOI:10.1007/s40291-025-00801-w

J Epidemiol Glob Health. 2025 Jul 31;15(1):100. doi: 10.1007/s44197-025-00421-x.

ABSTRACT

BACKGROUND: In Ethiopia’s Sidama National Regional State, diarrhea remains the second most common cause of illness among children under five, despite a decrease in its mortality rate. However, limited research has been conducted in Ethiopia to identify the causes behind the continuing rise in the prevalence of diarrhea in children associated with exposure to domestic animals. Therefore, this study explores the relationship between domestic animal, environmental, and human behavioral factors and confirmed cases of diarrhea in children under five in the Sidama National Regional State of Ethiopia.

METHODS: We conducted a matched-pairs case-control study involving 306 cases and 306 controls in the Sidama region from September 2022 to February 2023. Cases and controls were identified at healthcare facilities, and interviews and observations were completed at residential homes with children under five. We collected data using the KoboCollect application and analyzed it through conditional logistic regressions. The random forest (RF) method with the classification RF model was used to compare its findings with those of the multivariate conditional regression analysis. The statistical analyses were conducted using R v.4.3.2 software.

RESULTS: The study indicated that having a caretaker who is a housewife [matched adjusted odds ratio (mAOR) = 3.09, 5% CI (1.09, 8.70)], a mean number of chickens ≥ 5 [mAOR = 5.18, 95% CI (2.70, 9.95)], the absence of soap at handwashing facilities [mAOR = 2.61, 95% CI (1.34, 5.10)], those who travel more than 30 min to fetch water [mAOR = 3.14, 95% CI (1.13, 8.78)], children who are in contact with animal feces [mAOR = 2.44, 95% CI (1.24, 4.82)], and households living with animals [mAOR = 3.28, 95% CI (1.71, 6.30)] showed significant associations with under-five diarrhea. The random forest analysis also identified the first five variables as the main risk factors for diarrhea occurrence among children under-five years of age.

CONCLUSIONS: Risk factors for diarrhea among children under-five include a high number of chickens, cohabitation with animals, prolonged water-fetching times, poor hand hygiene, and caretakers’ occupational status. Animal feces management, improved water access, and hygiene education are critical to reducing under-five diarrheal diseases.

PMID:40742515 | DOI:10.1007/s44197-025-00421-x

Ultrasound J. 2025 Jul 31;17(1):37. doi: 10.1186/s13089-025-00441-5.

ABSTRACT

BACKGROUND: The efficacy of bedside chest ultrasonography for the detection and diagnosis of pneumothorax is under debate. We aimed to compare Emergency Healthcare Workers performed chest ultrasonography with chest X-ray in the detection and diagnosis of pneumothorax in the emergency department.

METHODS: We queried PubMed, Cochrane, ScienceDirect, Web of Science and ClinicalTrials.gov databases from 2000 through January 2024. We included all studies (both retrospective and prospective) that compared the diagnostic performance of chest ultrasonography with chest radiography, using chest computed tomography as the gold standard. Participants are patients consulting in the emergency department and physician that performed the chest ultrasound was an Emergency Healthcare Workers. Studies reporting the sensitivity and specificity for both chest ultrasonography and chest X-ray met inclusion criteria. We applied a random effects meta-analysis methodology. We then performed a meta-regression analysis to search for influencing variables such as technical parameters of echograph, patients and pneumothorax.

MAIN RESULTS: 15 studies totaling 3,171 patients were analyzed. 71% of patients were male with a mean age of 40.2 years. The mean prevalence of pneumothorax was 27.6% (95 CI 20.9 to 34.3). Chest ultrasonography had higher sensitivity (79.4%, 68.2 to 90.7) compared to chest X-ray (48.1%, 36.8 to 59.4), and a greater negative predictive value (chest ultrasonography = 94.3%, 91.2 to 97.3, and chest X-ray = 87.9%, 84.1 to 91.6). There was no statistical difference in specificity between the two modalities: chest ultrasonography 99.5%, 99 to 100 and chest X-ray 99.8%, 99.4 to 100) or in positive predictive value (chest ultrasonography 94.2%, 90.5 to 97.9 vs chest X-ray 96.7%,92 to 100). Characteristics of echograph or pneumothorax and patients sociodemographic did not influence results.

CONCLUSION: In this systematic review and meta-analysis, chest ultrasonography performed by Emergency Healthcare Workers, had greater sensitivity and negative predictive value than chest radiography for the diagnosis of pneumothorax in emergency department patients.

PMID:40742513 | DOI:10.1186/s13089-025-00441-5

Child Health Nurs Res. 2025 Jul;31(3):165-175. doi: 10.4094/chnr.2025.014. Epub 2025 Jul 31.

ABSTRACT

PURPOSE: This study aimed to identify the factors affecting the health promotion behavior of school-aged children informed by the Information-Motivation-Behavioral Skills Model.

METHODS: A cross-sectional study was conducted with 209 fifth- and sixth-grade elementary school students from Seoul, selected through convenience sampling. Data were collected from March 13 to 31, 2023, using a self-administered questionnaire. The questionnaire included validated tools that measured health literacy, attitude toward health behaviors, social support, self-efficacy, and health promotion behavior. Data were analyzed using descriptive statistics, Pearson’s correlation, and stepwise multiple regression, using IBM SPSS/WIN ver. 29.0.

RESULTS: The factors influencing the health promotion behavior of school-aged children were social support (β=.43, p<.001), attitude toward health behaviors (β=.27, p<.001), interest in health (high interest group) (β=.14, p=.003), self-efficacy (β=.13, p=.014), and health literacy (β=.10, p=.026). The explanatory power of the model was 63% (F=68.37, p<.001).

CONCLUSION: Based on the results of this study, it is highly recommended to develop and apply health education and health promotion programs that consider health literacy, attitude toward health behaviors, social support, self-efficacy, and interest in health to foster school-aged children’s health promotion behavior.

PMID:40741628 | DOI:10.4094/chnr.2025.014

Tzu Chi Med J. 2025 May 9;37(3):321-327. doi: 10.4103/tcmj.tcmj_249_24. eCollection 2025 Jul-Sep.

ABSTRACT

OBJECTIVES: Transplantation of human umbilical cord blood cells (hUCB) may enhance neuroprotection, and thus, the intravenous (IV) infusion of hUCB in patients with acute ischemic stroke (AIS) is being tested for its safety and efficacy.

MATERIALS AND METHODS: We conducted a 12-month, open-label, and single-center, phase I trial of hUCB treatment in AIS patients at the age of 45-80 years, with magnetic resonance imaging evidence of acute infarction in the internal carotid artery supplied territory and the National Institute of Health Stroke Scale (NIHSS) score between 6 and 18. Eligible participants received a single-dose IV infusion of hUCB followed by the two doses of mannitol infusion within 9 days after the onset of stroke symptoms. The primary endpoint was the incidence of adverse events (AEs) and the secondary endpoints were the changes in NIHSS, Barthel index (BI), and Berg Balance Scale (BBS) scores.

RESULTS: Six patients (Male: Female = 3: 3) were enrolled with a mean age at 65.8 years. A total of 40 AEs occurred in six participants during this study, which included nine serious adverse events. Only transient erythema multiforme and hematuria were probably and possibly related to hUCB infusion, respectively. The mean NIHSS score was 11.5 at baseline and it significantly improved at 1, 3, 6, 9, and 12 months after treatment (mean change from baseline: -4.0, -5.3, -6.8, -7.0, and -7.3). The mean BI score was 22.5 at baseline and it significantly increased at 3 and 6 months after treatment (mean change from baseline: 26.7 and 42.5, respectively). The BBS score increased numerically but did not reach statistical significance. The changes in cytokine levels and spleen size were unremarkable.

CONCLUSION: The IV hUCB was safe and well tolerated in AIS patients, and the preliminary efficacy results demonstrated its therapeutic potential, supporting the conduct of a randomized, placebo controlled, phase II clinical trial in future.

PMID:40741608 | PMC:PMC12306862 | DOI:10.4103/tcmj.tcmj_249_24

Cureus. 2025 Jun 30;17(6):e87035. doi: 10.7759/cureus.87035. eCollection 2025 Jun.

ABSTRACT

INTRODUCTION: Necrotising soft tissue infection (NSTI) is uncommon, and its management is complex due to its diverse clinical presentations, multiple associated comorbidities, and a wide range of potential microbial aetiologies. This study aims to illustrate the clinical profile, microbiological spectrum, and factors affecting mortality among patients with NSTI.

METHODS: This single-centre, hospital-based, prospective observational study included all patients with NSTI aged 18 years or older. The primary outcome was the impact of time to surgery on mortality. Secondary outcomes included identifying the aetiology, microbiological flora, major co-morbidities, and overall outcomes in these patients. Results: During the study period, 87 patients were enrolled. There were 65 (74.7%) male and 22(25.3%) female patients with an age range of 18 years to 88 years. Postoperatively, 18 patients succumbed to death, while 69 survived. Overall, the average timing of the first intervention after admission was six hours, with no significant statistical difference between the survivor and non-survivor group (p-value = 0.575). Our study found types I and II infections in 26 (34.5%) and 45 (65.4%) patients, respectively, and Escherichia coli (E. coli) was the most common isolate in both types. The antibiotic resistance pattern revealed increased resistance to third-generation cephalosporins and fluoroquinolones for the Enterobacteriaceae group and E. coli.

CONCLUSION: High APACHE II and LRINEC scores, anaemia, hypoalbuminemia, and high creatinine are associated with a higher risk of death. Prompt multidisciplinary management of these patients significantly improves outcomes and reduces mortality.

PMID:40741589 | PMC:PMC12309787 | DOI:10.7759/cureus.87035

Cureus. 2025 Jun 30;17(6):e87049. doi: 10.7759/cureus.87049. eCollection 2025 Jun.

ABSTRACT

Real-world data on cardiovascular immune-related adverse events (CV-irAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs) present findings that differ from those reported in meta-analyses of clinical trials. This study aims to estimate the incidence of CV-irAEs from observational studies among patients undergoing ICI therapy for various malignancies and investigate the discrepancy between the results of meta-analyses and observational studies. A systematic literature review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. The PubMed database was searched for observational studies that included cancer patients treated with ICIs. Α single-arm meta-analysis using the metaprop command in Stata Statistical Software: Release 16 (StataCorp LLC, College Station, Texas, United States) was performed for the following outcomes: myocarditis, pericardial disease, arrhythmias, cardiac failure, Takotsubo cardiomyopathy, ischemic heart disease, heart valve disease, venous thromboembolism and artery disease. ICI treatment agents were classified into three major classes: PD-1 inhibitors, PD-L1 inhibitors, CTLA4 inhibitors, or their combinations. Heterogeneity was quantified using the I2 statistic and small study effect, and potential publication bias was assessed by inspecting funnel plots, as well as by Egger’s test. A total of 42 studies were included. The incidence of CV-irAEs within the entire population undergoing treatment with ICIs was assessed as follows: total CV-irAEs: 8% (95% confidence interval (CI): 6%, 10%), arrhythmias: 18% (95%CI: 10%, 27%), myocarditis: 11% (95%CI: 5%, 18%), cardiac failure: 8% (95%CI: 2%, 15%), ischemic heart disease: 6% (95%CI: 3%, 11%), pericardial disease: 5% (95%CI: 1%, 10%), artery disease 5% (95%CI: 1%, 12%), and venous thromboembolism: 3% (95%CI: 0%, 8%); cardiomyopathy and heart valve disease had minimal number of observed episodes, thus the pooled incidence results are referring as zero, 0% (95%CI: 0%, 0%) and total CV deaths: 1% (95%CI: 0%, 3%). Median time to CV-irAEs was estimated at 119 days (interquartile range (IQR) 53-180). The most common CV-irAEs were arrhythmias, myocarditis, and cardiac failure with life-threatening complications. Data derived from meta-analyses of clinical trials in most cases indicated that the total incidence of CV-irAEs varied between 0.05% and 1.30%, while in large pharmacovigilance databases, it ranged from 0.125% to 6.7%. In our meta-analysis of post-market surveillance studies, higher estimates were obtained, which offer an insight into the long-term prevalence and outcomes for patients experiencing CV complications associated with ICIs. Longer follow-up period and different definitions of cardiotoxicity may account for the higher cardiotoxicity rates that seem to reflect an emerging threat.

PMID:40741581 | PMC:PMC12310155 | DOI:10.7759/cureus.87049

Cureus. 2025 Jun 30;17(6):e87033. doi: 10.7759/cureus.87033. eCollection 2025 Jun.

ABSTRACT

The treatment of distal tibial fractures with an articular fracture line remains controversial. Intramedullary nailing allows for the maintenance of good frontal and sagittal alignment, as well as rapid and satisfactory functional recovery. In this retrospective case series, we present our department’s experience with 20 patients presenting with AO 43C1 and 43C2 fractures, treated with intramedullary nailing combined with interfragmentary screw fixation over an eight-year period, with a follow-up of 18 months. Postoperative alignment was assessed using radiographic measurements of the anterior distal tibial angle (ADTA) and lateral distal tibial angle (LDTA), immediately and at follow-up. Functional outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. Descriptive statistical analysis was used to report means, standard deviations, and proportions. Acceptable alignment was achieved in 95% of patients. The AOFAS score exceeded 86% in 88% of patients, indicating excellent outcomes. Interfragmentary screw fixation prior to nailing improved construct stability, minimized malalignment risk, and enhanced functional recovery.

PMID:40741563 | PMC:PMC12309624 | DOI:10.7759/cureus.87033