Category: Nevin Manimala

Epileptic Disord. 2026 Apr 8. doi: 10.1002/epd2.70232. Online ahead of print.

ABSTRACT

OBJECTIVES: Antiseizure medications (ASMs) can induce the activity of drug-metabolizing enzymes and drug transporters, including cytochrome P450 (CYP)2C9 and P-glycoprotein (P-gp). Our objective was to comparatively assess the effects of ASMs on exposure to clinical CYP2C9 and P-gp substrates.

METHODS: This systematic review and network meta-analysis (NMA) was registered in PROSPERO (CRD42023473609) and performed following PRISMA 2020 guidelines. MEDLINE, EMBASE, and Cochrane Library were searched until October 22, 2025, with additional searches conducted in the FDA and EMA databases and ClinicalTrial.gov. Studies were included if they were prospective and the ASM was used as monotherapy for ≥5 days. The primary endpoint was the substrate area under the curve ratio (AUCR) with/without the ASM. Treatments were ranked by P-scores (range 0-1, higher values reflect stronger induction). The point estimate for indirect pairwise comparisons was the standardized mean difference (SMD). Bias risk was assessed using the PKclin tool.

RESULTS: Twelve and six interventional pharmacokinetic studies with 227 and 97 participants were included in the CYP2C9 and P-gp NMAs, respectively. The ASM with the greatest CYP2C9 induction potential was carbamazepine (600 mg/day, P-score .78). The only statistically significant effect size estimate for CYP2C9 was obtained in the comparison between carbamazepine 600 mg/day and cenobamate 200 mg/day (SMD -.42; CI -.76, -.09). Carbamazepine (300 or 600 mg/day) was also the strongest P-gp inducer (P-scores, .79 and .55, respectively). The effects of its two doses did not differ, and 300 mg/day had a stronger effect on P-gp compared with the other ASMs.

SIGNIFICANCE: Despite variability in populations, substrate drugs, and doses, our findings demonstrate that carbamazepine is an inducer at 300 mg/day, and that ASMs can rank differently as CYP2C9 versus P-gp inducers. Therefore, the safety of ASM polytherapy cannot be extrapolated from one pathway to another for treatment selection, for example, for post-stroke epilepsy.

PMID:41948839 | DOI:10.1002/epd2.70232

Am J Clin Pathol. 2026 Apr 3;165(4):aqag024. doi: 10.1093/ajcp/aqag024.

ABSTRACT

OBJECTIVES: Cancer is a leading cause of mortality worldwide, yet access to specialized pathology services remains limited in many low- and middle-income countries, including Tanzania. Telepathology offers a practical means to expand diagnostic capacity and improve timely cancer care. Through a partnership with the American Society for Clinical Pathology (ASCP) and Duke University, Kilimanjaro Christian Medical Centre (KCMC) implemented a telepathology consultation platform to provide expert review for diagnostically challenging cases.

METHODS: This cross-sectional observational study analyzed challenging pathology cases submitted for teleconsultation between September 2018 and March 2025. Whole-slide images were reviewed by pathologists from Duke University, Radboud University Medical Centre, Princess Máxima Center, ASCP-Tanzania, and the Medical College of Wisconsin. Diagnostic concordance between local and expert interpretations was measured. Turnaround time (TAT) and subspecialty variation were analyzed using descriptive statistics and χ2 testing.

RESULTS: A total of 1266 cases were reviewed, representing 16 different subspecialties. Hematopathology (28.4%), head and neck pathology (17.1%), and soft tissue pathology (9.9%) were the most frequently consulted. The overall concordance rate was 44.79% (567/1266), with a partial concordance rate of 19.75% (250/1266) and a discordance rate of 32.78% (415/1266). Concordance varied significantly across subspecialties (χ2(15) = 31.90, P = .0066). The mean TAT was 18.3 days, with a downward trend from 2018 to 2025.

CONCLUSIONS: Implementation of telepathology at KCMC is feasible and provides a sustainable model for expanding access to expert pathology consultation in resource-limited settings. Despite modest concordance rates, telepathology enhanced diagnostic accuracy, education, and quality assurance, while TATs improved over the study period. Continued investment is needed in digital infrastructure.

PMID:41948834 | DOI:10.1093/ajcp/aqag024

Stroke. 2026 Apr 8. doi: 10.1161/STROKEAHA.125.054863. Online ahead of print.

ABSTRACT

Management of unruptured intracranial aneurysms requires balancing the risk of aneurysm rupture against the risk of procedural complications. Estimates of rupture risk stem from a few landmark natural history studies whose findings differ substantially, creating uncertainty for clinical decision-making. This review appraises these studies, highlighting areas of agreement and contradiction to inform future directions. Across studies, short-term rupture risk is low and increases with aneurysm size. The magnitude of risk varies (0.20%-1.85% at 1 year). These discrepancies likely arise from methodological challenges inherent to natural history research, including selection, crossover, incomplete follow-up, and regional variation. The effects of these factors are difficult to disentangle due to confounding. Rupture risk is highest in Finnish studies, followed by Japanese, then other international cohorts. This geographic pattern is reversed for the treatment rate. Rupture risk also shows a strong inverse relationship with treatment rate (P=0.008, R²=0.79). This makes it impossible to know whether rupture risk reflects treatment or geography, and which estimates apply clinically. Studies have short follow-up (mean 2.8 years) and require substantial extrapolation to estimate lifetime risk (mean age at diagnosis 42-66 years). Small differences in short-term estimates produce large variations in long-term projections. Moreover, the underlying assumption that risk remains constant with time has not been formally evaluated. Half of the data sets are consistent with this, but half suggest it declines with time. The effects of key aneurysm rupture predictors vary between studies. This includes age, sex, hypertension, smoking, prior subarachnoid hemorrhage, family history of intracranial aneurysms, and aneurysm location, multiplicity, and size thresholds. It is unclear whether this reflects regional variation, overfitting, or other factors. Meta-analyses are most representative, but remain constrained by limitations of contributing data sets. Larger multicenter studies with longer follow-up, fewer losses, and deeper phenotyping are still needed, despite their practical challenges.

PMID:41948814 | DOI:10.1161/STROKEAHA.125.054863

Disaster Med Public Health Prep. 2026 Apr 8;20:e82. doi: 10.1017/dmp.2026.10353.

ABSTRACT

OBJECTIVES: Hazardous materials (HazMat) incidents pose significant risks to public health, safety, and the environment. This study aimed to characterize the temporal trends, geographic distribution, operational settings, and incident types of HazMat events reported in Oman.

METHODS: This retrospective descriptive study analyzed data from the national HazMat incident records maintained by the Civil Defence and Ambulance Authority (CDAA). All reported chemical, biological, or radiological incidents between June 1, 2019, and November 30, 2024, were included.

RESULTS: A total of 55 HazMat incidents were recorded during the study period. Reported incidents increased over time, with the highest annual counts observed in 2023 (14 incidents) and 2024 (17 incidents). Muscat Governorate accounted for 39 incidents (71%). Residential neighborhoods were the most common operational setting (26/55, 47%), followed by other public areas (9/55, 16%), while airports, educational institutions, industrial areas, and transportation corridors each accounted for 5 incidents (9%). Gas leaks were the most frequently reported incident type, involved in 28 incidents (51%).

CONCLUSIONS: HazMat incidents in Oman increased over the study period and were concentrated in Muscat Governorate. Incidents occurred across diverse operational settings, particularly residential and public environments, while gas leaks represented the most frequently reported incident type.

PMID:41948793 | DOI:10.1017/dmp.2026.10353

JPRAS Open. 2026 Mar 7;49:358-365. doi: 10.1016/j.jpra.2026.03.014. eCollection 2026 May.

ABSTRACT

BACKGROUND: Necrotizing fasciitis (NF) is a rapidly progressing, life-threatening soft tissue infection. Procalcitonin (PCT) has emerged as a promising biomarker for early diagnosis and prognosis in severe infections.

METHODS: We performed a retrospective analysis of 62 patients with confirmed NF treated at a high-volume Department of Plastic Surgery between January 2005 and May 2024. Clinical parameters, laboratory values, and surgical outcomes were evaluated. Patients were stratified into survivors and non-survivors.

RESULTS: Elevated PCT levels at admission were significantly associated with in-hospital mortality (p = 0.0329), whereas other parameters showed no statistical significance. Skin grafting was the most common reconstructive procedure. No significant association was found between the type of reconstructive surgery and survival.

CONCLUSION: Serum PCT levels at admission may serve as a valuable prognostic marker in NF. Once infection control is achieved, reconstructive surgical interventions appear to be safe and do not influence survival.

PMID:41948778 | PMC:PMC13051722 | DOI:10.1016/j.jpra.2026.03.014

Pediatr Qual Saf. 2026 Apr 6;11(2):e876. doi: 10.1097/pq9.0000000000000876. eCollection 2026 Mar-Apr.

ABSTRACT

INTRODUCTION: Emergency department evaluations for acute child sexual assault include anogenital photodocumentation as a standard of care, which has implications for accurate clinical care and forensic significance. If photodocumentation quality is suboptimal from a diagnostic standpoint, this may lead to wasted care and resources and place needless burdens on patients and families. Our project aimed to improve the diagnostic quality of anogenital photodocumentation at 2 sites in a pediatric emergency department, increasing it from a baseline of 24% to 50% during a 9-month intervention period.

METHODS: We surveyed multiple clinical teams to determine drivers of diagnostic quality. Using the Model for Improvement, we implemented multiple interventions (clinical pathway revisions, visual guidance, direct provider feedback, and an improved light source option) in the care process for these patients and measured diagnostic quality using a definition adapted from a validated photograph-scoring system. We used statistical process control charts to track diagnostic quality.

RESULTS: We detected no special-cause variation in the outcome measure of improved diagnostic quality. We detected special-cause variation for the process measure of whether care teams obtained photodocumentation, which increased from 77% to 89%.

CONCLUSIONS: Interventions to improve the diagnostic quality of anogenital photodocumentation did not result in improvement; however, there was improvement in the likelihood of care teams obtaining photodocumentation in acute sexual assault evaluations.

PMID:41948737 | PMC:PMC13052962 | DOI:10.1097/pq9.0000000000000876

Front Pharmacol. 2026 Mar 23;17:1792080. doi: 10.3389/fphar.2026.1792080. eCollection 2026.

ABSTRACT

INTRODUCTION: The Home Medication Review (HMR) is a structured, patient-centred service provided by pharmacists to facilitate the optimisation of medication therapy, mitigate drug-related issues, and improve health outcomes. Despite the global adoption of HMR, there is a lack of standardisation. To overcome this gap, a detailed HMR checklist was developed to ensure that all key elements of an HMR visit are covered. The aim was to develop and validate a comprehensive checklist to standardise the delivery of HMR and facilitate its widespread implementation in the Indian healthcare system, which can also be adopted internationally with regional modifications.

METHODS: A detailed literature review was conducted to develop a preliminary checklist framework, which was subsequently refined through input from a seven-member advisory board. Content Validity Index (CVI) and modified kappa statistics (k*) were used to evaluate content validity by eleven experts. The checklist was tested for its usability in the home care environment through pharmacist-conducted reviews of medications in a feasibility study involving 20 participants.

RESULTS: The 12-domain, final 65-item HMR Checklist demonstrated high levels of content validity, with an average Cronbach’s alpha (Ave-CVI) of 0.97, indicating high relevance and simplicity. In the case of Universal Agreement-CVI, the values were 0.78 and 0.75. The level of pharmacist compliance during the feasibility tests showed a high level of adherence (93.5% total compliance), with key areas demonstrating adherence at every visit. Further examination of the I-CVI and k* values was very high in all domains, demonstrating good item-level validity. Overall, the feasibility data demonstrated high patient acceptance and easy integration into the workflow.

CONCLUSION: Overall, content validity indices and content validation processes are considered crucial factors in the development of an instrument. The study demonstrates that the HMR Checklist is a reliable, holistic, and practical instrument that can be used to standardise and implement home medication reviews, led by clinical pharmacists. It has a strong potential to enhance medication safety and provides a solid foundation for future large-scale evaluations globally.

PMID:41948732 | PMC:PMC13050876 | DOI:10.3389/fphar.2026.1792080

Front Pharmacol. 2026 Mar 23;17:1670012. doi: 10.3389/fphar.2026.1670012. eCollection 2026.

ABSTRACT

OBJECTIVE: Apatinib combined with S-1 and oxaliplatin (SOX) synergistically improves the prognosis of advanced gastric cancer patients, but its application as an adjuvant regimen has rarely been reported. This study aimed to investigate the efficacy and safety of adjuvant low-dose apatinib combined with SOX versus SOX alone in patients with resectable locally advanced gastric cancer.

METHODS: This cohort study included 110 patients with locally advanced gastric cancer (pTNM stage III) who underwent radical surgery. Among these patients, 70 patients received adjuvant low-dose apatinib (250 mg/day) combined with SOX regimen (named apatinib + SOX group), and 40 patients received adjuvant SOX regimen alone (named SOX group). Disease-free survival (DFS) and adverse events were recorded.

RESULTS: DFS was longer in apatinib + SOX group versus SOX group (P = 0.004). Specifically, the median DFS was not reached, and the 1-year/2-year cumulating DFS rates reached 75.7%/61.4% in apatinib + SOX group, whereas the median DFS was 15.0 (95% confidence interval: 10.0-20.0) months, and the 1-year/2-year accumulating DFS rates were 57.5%/35.0% in SOX group. After adjustment by multivariate Cox regression, apatinib + SOX (versus SOX) was independently related to prolonged DFS (hazard ratio = 0.316, P < 0.001). Moreover, hypertension showed a higher tendency in apatinib + SOX group compared to SOX group (22.9% versus 10.0%, P = 0.093), but did not reach statistical significance. However, incidences of other adverse events were not different between the two groups including: nausea and vomiting (P = 1.000), fatigue (P = 0.709), leukopenia (P = 0.103), pain (P = 0.564), thrombocytopenia (P = 0.113), anorexia (P = 0.564), and anemia (P = 0.686).

CONCLUSION: Low-dose apatinib combined with SOX may be a feasible adjuvant regimen in patients with resectable locally advanced gastric cancer.

PMID:41948723 | PMC:PMC13051217 | DOI:10.3389/fphar.2026.1670012

Front Pharmacol. 2026 Mar 23;17:1789772. doi: 10.3389/fphar.2026.1789772. eCollection 2026.

ABSTRACT

OBJECTIVE: Pomiferin, a prenylated isoflavonoid from Maclura pomifera, shows anticancer and antioxidant potential. However, data vary across cell lines and models. This meta-analysis aims to quantify its IC ₅₀ in different cancer types and systematically synthesise its effects on oxidative stress biomarkers, thereby establishing a quantitative synthesis for its therapeutic profile.

METHODS: A systematic search in PubMed, Scopus, and Web of Science was conducted following PRISMA guidelines. A “mean-only” approach was used to manage within-study dependency and inconsistent variance reporting. Data were analysed with multilevel random-effects models and Cluster-Robust Variance Estimation (CR2).

RESULTS: The pooled geometric mean IC ₅₀ for Pomiferin was 12.6 μM (logIC ₅₀ = 2.53). Meta-regression showed that efficacy varied by tumour type, with Glioma/neurological models having higher IC ₅₀ values (lower efficacy) than others (p = 0.012). Pomiferin increased Catalase activity (p = 0.044) and protein levels (p = 0.033). No statistically significant difference in efficacy was detected between in vitro and in vivo models (p = 0.190); however, current data limitations preclude establishing definitive biological equivalence.

CONCLUSION: This meta-analysis demonstrates that Pomiferin is a context-dependent agent that modulates enzymatic defences, such as CAT, confirming its potential as a therapeutic candidate. It highlights the efficacy limits in resistant types, such as Glioma, and provides a quantitative basis for future research. This study consolidates diverse findings into a robust evidence base, serving as the first comprehensive meta-analysis of Pomiferin’s biological activity and guiding future studies.

PMID:41948722 | PMC:PMC13050899 | DOI:10.3389/fphar.2026.1789772

J Kidney Cancer VHL. 2026 Apr 1;13(1):27-32. doi: 10.15586/jkc.v13i1.421. eCollection 2026.

ABSTRACT

To evaluate whether the length of positive surgical margin carries a risk for recurrence, data of patients that underwent partial nephrectomy (PN) from six centers were evaluated. Fifty-three patints with positive surgical margins (PSMs) (the PSM group) and 438 patients with negative surgical margin (the NSM group) were included in the present study. Pathologic reevaluations were performed, and surgical margins were measured in micrometers. The number of positive margin areas, and the length of the maximum and total positive margins were evaluated. Data were analyzed using SPSS 27 package program. A p-value less than 0.001 was considered statistically significant. Local recurrence occured in 16.98% of patients in the PSM group and 4.24% of patients in the NSM group. (p<0.001). Patients with PSM were at fourfold increased risk for recurrence. Age, gender, tumor location, tumor side and size, and fuhrman grade were not associated with local recurrence of the tumor (p>0.01). However, positive surgical margin was an important risk factor for local recurrence (p<0.01). No relationship was found between positive margin length and local recurrence (p=0.044). Logistic regression analysis did not identify any parameters associated with local recurrence. The presence of a PSM was significantly associated with an increased risk of local recurrence following PN. The number of positive margin foci and total or maximum length of margin involvement were not associated with recurrence. These findings suggest that it is the presence of PSM, rather than its extent, that may be the primary factor influencing oncological risk.

PMID:41948714 | PMC:PMC13051508 | DOI:10.15586/jkc.v13i1.421