Tag: nevin manimala

Pharmaceut Med. 2026 May 4. doi: 10.1007/s40290-026-00607-z. Online ahead of print.

ABSTRACT

BACKGROUND: Children remain underrepresented in clinical research, despite regulatory frameworks like the EU Paediatric Regulation and Paediatric Investigation Plans (PIPs). The 2024 Declaration of Helsinki revision now recognises excluding vulnerable populations from research as a potential ethical concern. The Clinical Trial Regulation (EU) No 536/2014 aims to harmonise clinical trial application assessment procedures through a coordinated process involving a Reporting Member State (RMS) and Member States Concerned (MSCs).

AIMS: To determine if harmonisation is occurring, we conducted the first systematic analysis of Phase I/II paediatric trial application assessments across Member States (MS) in the European Union (EU) focusing on assessment variability, evidence requirements, PIP integration, and adolescent inclusion practices in adult trials.

METHODS: In the context of a fellowship at the European Medicines Agency, non-public data of 160 paediatric Clinical Trial Applications (CTAs) submitted through the Clinical Trial Information System (January 2022-July 2024) were screened, with inclusion of 55 Phase I/II trials in the main analysis (selected for their focus on innovative treatments and complex risk-benefit assessments). For each CTA, requests for information (consisting of considerations stated by the RMS and MSCs), assessment reports, sponsor responses, and PIP documentation were reviewed. The number of considerations in the requests for information per MS was analysed with median values calculated. Also, considerations were systemically categorised and assessment patterns between RMS and MSC roles were compared. It was examined how PIPs were integrated into assessments and approaches to adolescent inclusion in adult trials was analysed through systematic review of MS considerations.

RESULTS: Of the 160 paediatric CTAs screened, 145 received authorisation, 10 were not authorised, and 5 were withdrawn. Among the 145 authorised CTAs, 61 were Phase I/II trials, 55 of which were included in the main analysis. Analysis of these applications revealed significant heterogeneity in both the number and type of considerations raised across MS, with the median number of considerations per CTA ranging from 5.5 to 26 across MSs (p = 0.025), with particularly marked variation when MSs acted as MSCs compared to RMSs-where additional considerations ranged from zero to 25 per CTA on top of those raised by the RMS. In 36% (20/55), MSs raised concerns about insufficient (pre-)clinical evidence pointing to divergent interpretations of evidence requirements. The degree to which PIPs were integrated into CTA assessments varied considerably-ranging from strict adherence to PIP elements to minimal consideration. In 92% (11/12), MSs showed reluctance to include adolescents in adult Phase I/II trials.

CONCLUSIONS: Despite the CTR’s harmonisation goals, substantial variations persist in assessment practices across MSs, particularly regarding evidence requirements, PIP integration, and adolescent inclusion in adult trials. These variations directly impact equitable access to clinical trials for children across the EU. Urgent regulatory guidance is needed to align interpretation of evidence standards, clarify the role of PIPs in CTA evaluation, and support evidence-based approaches to adolescent inclusion in adult trials.

PMID:42081189 | DOI:10.1007/s40290-026-00607-z

Am J Reprod Immunol. 2026 May;95(5):e70250. doi: 10.1111/aji.70250.

ABSTRACT

PROBLEM: Female genital mutilation/cutting (FGM/C) is harmful to physical, mental, and reproductive health, though the effect of this practice on a woman’s HIV susceptibility is poorly understood. Despite the known associations of FGM/C with short-term vaginal epithelial damage, neither genital inflammation nor the genital microbiome have been explored in women who have undergone FGM/C. In this study we compare the genital immune milieu and microbiome among female sex workers (FSWs) by FGM/C status, hypothesizing that these biological factors are dysregulated in women who have undergone FGM/C, heightening their risk of HIV acquisition.

METHOD OF STUDY: 1003 FSWs in Nairobi, Kenya, were enrolled in the Maisha Fiti study and visited a study clinic up to three times from June 2019 to March 2021. Participants self-reported any previous exposure to FGM/C as well as other relevant sociodemographic factors. Levels of proinflammatory cytokines and soluble E-cadherin (sE-cad), a biomarker of epithelial barrier disruption, were measured by multiplex immunoassay using self-collected cervicovaginal secretion samples provided by HIV-uninfected participants. Genital inflammation was defined using a composite score of inflammatory cytokines previously associated with HIV acquisition. The presence of inflammation was compared longitudinally between groups using mixed models to control for potential confounders including age, bacterial vaginosis (BV) status as defined by Nugent score, and others. Vaginal bacterial abundance, Shannon diversity, and total levels of key vaginal bacteria were measured by qPCR and compared by FGM/C status in an exploratory analysis.

RESULTS: 44 of 1003 (4%) participants had undergone Type I or II FGM/C. These participants were older (p < 0.001) and more likely to test positive for herpes simplex virus-2 (HSV-2; p = 0.04), and less likely to have completed primary education (p = 0.03). Among HIV-uninfected participants, there was no evidence that genital inflammation was associated with FGM/C status after controlling for potential confounders (aOR = 0.70; 95% CI: 0.31-1.59; p = 0.40). There was no evidence of a difference in BV prevalence (p > 0.99), total bacterial abundance (p = 0.96), or Shannon diversity (p = 0.15) by FGM/C status.

CONCLUSIONS: Type I or II FGM/C was not associated with genital inflammation or microbial dysregulation in the long-term among HIV-negative FSWs in this cohort. This may be due to the duration elapsed since FGM/C occurred or the lowered mucosal immune activation previously observed in FSWs.

PMID:42081188 | DOI:10.1111/aji.70250

Discov Nano. 2026 May 4;21(1):163. doi: 10.1186/s11671-026-04597-4.

ABSTRACT

This study examines magnetohydrodynamic (MHD) heat and mass transfer of a ternary hybrid nanofluid over a rotating sphere incorporating thermophoretic particle deposition, thermal radiation, activation energy and chemical reaction effects. The nanofluid consists of [Formula: see text]-[Formula: see text]-[Formula: see text] nanoparticles dispersed in propylene glycol. The governing boundary layer equations are transformed into a system of nonlinear ordinary differential equations via similarity transformations, which are solved using the Gegenbauer wavelet method. Results indicate that increasing magnetic interaction suppresses velocity due to Lorentz force effects while enhancing thermal distribution. Higher nanoparticle volume fraction improves heat transfer but increases viscous resistance. Thermophoresis and activation energy significantly influence mass transfer characteristics. Comparative analysis reveals that the ternary hybrid nanofluid exhibits enhanced thermal performance relative to the corresponding hybrid nanofluid configuration. The findings provide theoretical insight into MHD-controlled rotating nanofluid systems.

PMID:42081179 | DOI:10.1186/s11671-026-04597-4

Clin Transplant. 2026 May;40(5):e70551. doi: 10.1111/ctr.70551.

ABSTRACT

OBJECTIVE: To evaluate whether the difficulty of surgery affects failure-to-rescue (FTR) after liver transplantation (LT).

SUMMARY BACKGROUND DATA: Predictors of FTR include both recipient and intraoperative factors, and their identification and improvement may reduce its incidence.

METHODS: This retrospective study included all first-time isolated LTs performed in six centers. A difficult LT was defined as one in which the number of blood units transfused, cold ischemia time, and duration of surgery were all at or above the median values for the study population. FTR was defined as death within 90 days after a major postoperative complication. The correlations of a difficult LT with outcomes, including FTR, were assessed. Predictors of FTR were identified.

RESULTS: The study population included 1341 patients. The respective incidences of difficult LT, 90-day major complications, 90-day mortality, and FTR were 17.4%, 53.6%, 5.8%, and 10.7%. Difficult LT was correlated with worse short-term outcomes, including a high FTR rate. Being in the intensive care unit, receiving renal replacement therapy at the time of LT, and difficult LT were independent predictors of FTR.

CONCLUSIONS: Mortality following a difficult LT may be correlated to FTR. Identification of modifiable predictors of FTR may help to improve the post-transplant management of these patients.

PMID:42081175 | DOI:10.1111/ctr.70551

Ophthalmic Physiol Opt. 2026 May 4. doi: 10.1007/s44402-026-00097-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the growth and prescribing patterns of community-based independent prescribing (IP) optometrists managing acute eye conditions in Wales between 2020 and 2024, a period that saw the introduction and subsequent commissioning of National Health Service (NHS) funded acute eye care with prescribing in primary care optometry throughout Wales.

METHODS: Monthly prescribing data from NHS Wales Shared Services Partnership were analysed for all IP optometrists in Wales from 1st February 2020 to 31st January 2024. Data included drug name, British National Formulary classification, quantity, cost and health board location. Descriptive and correlational statistics were used to assess prescribing activity, regional distribution and cost trends.

RESULTS: The number of active IP optometry practices increased from eight in February 2020 to 68 in January 2024, with 20,980 prescriptions (49,162 items) issued at a total cost of £339,426. Corticosteroids, anti-infective agents and ocular lubricants were the most frequently prescribed drug classes. Ocular lubricants accounted for 34.0% of the total spend. Regional variation in prescribing activity was observed, with positive correlations between the number of active practices and both prescription volume and cost. Generic prescribing accounted for 47.0% of prescriptions, lower than national averages.

CONCLUSION: NHS commissioning of IP services in Wales has significantly expanded the role of optometrists in managing acute eye conditions in primary care. The findings highlight the potential of IP optometry to reduce pressure on general medical practice and hospital eye services. Further research is needed to evaluate clinical outcomes, cost-effectiveness and the broader therapeutic use of ocular lubricants in acute care.

PMID:42081174 | DOI:10.1007/s44402-026-00097-1

J Endocrinol Invest. 2026 May 4. doi: 10.1007/s40618-026-02899-z. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the associations between composite inflammatory indicators and the presence of osteoporosis (OP) and sarcopenia in patients with type 2 diabetes mellitus (T2DM), and to explore the potential mediating role of inflammation in the relationship between sarcopenia and OP.

METHODS: In this cross-sectional study, 756 adults with T2DM were enrolled. Osteoporosis was defined as a Bone Mineral Density (BMD) T-score ≤ -2.5 at the hip or lumbar spine. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Composite inflammatory indicators, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), pan-immune inflammation value (PIV), platelet-to-lymphocyte ratio (PLR), advanced lung cancer inflammation index (ALI), neutrophil-to-albumin percentage ratio (NPAR), platelet-to-neutrophil ratio (PNR), and neutrophil-lymphocyte-platelet ratio (NLPR) were calculated from routine blood parameters. Associations between composite inflammatory indicators and OP as well as sarcopenia were assessed using restricted cubic splines (RCS) and multivariate logistic regression analysis. The ability of composite inflammatory indicators to identify sarcopenia was evaluated using receiver operating characteristic (ROC) curves. Mediation analysis to assess the indirect effect of inflammation on the sarcopenia and osteoporosis relationship.

RESULTS: In this study, the prevalence of osteoporosis was 31.1%, and the prevalence of sarcopenia was 34.0%. RCS analysis revealed that ALI exhibited a linear negative correlation with osteoporosis, and SII, SIRI, NLR, PIV, PLR, NLPR, NPAR exhibited linear positive correlations with sarcopenia (all P for nonlinearity > 0.05). PNR and ALI demonstrated a negative nonlinear association with sarcopenia (all P for nonlinearity < 0.05). Logistic regression analysis indicated that sarcopenia was positively associated with osteoporosis (P< 0.05). However, ALI (aOR 0.99, 95% CI 0.98-1.00) showed inverse association with osteoporosis (P < 0.05). Logistic regression analysis also indicated that osteoporosis was positively associated with sarcopenia (P < 0.05). The multivariable regression analysis showed hs-CRR (aOR 1.03, 95% CI 1.01-1.05), SII (aOR 1.00, 95% CI 1.00-1.00), SIRI (aOR 1.46, 95% CI 1.13-1.93), PIV (aOR 1.00, 95% CI 1.00-1.00), NPAR (aOR 1.11, 95% CI 1.04-1.19), and NLR (aOR 1.20, 95% CI 1.05-1.38) showed positive associations with sarcopenia. Conversely, ALI (aOR 0.98, 95% CI 0.97-0.99) exhibited a inverse association with sarcopenia (P < 0.05). The area under the ROC curve (AUC) for ALI in identifying sarcopenia was 0.68. Mediation analysis showed that ALI mediated the statistical association between sarcopenia and osteoporosis with proportions (%) of 19.58.

CONCLUSION: Sarcopenia is positively associated with osteoporosis in patients with T2DM, and this relationship is partially mediated by systemic inflammation, as captured by the ALI. The ALI may serve as a useful and accessible clinical indicator to identify T2DM patients at higher risk for sarcopenia and osteoporosis, who may benefit from targeted screening and multimodal interventions.

PMID:42081166 | DOI:10.1007/s40618-026-02899-z

Acta Biotheor. 2026 May 4;74(3):14. doi: 10.1007/s10441-026-09523-w.

NO ABSTRACT

PMID:42081161 | DOI:10.1007/s10441-026-09523-w

Support Care Cancer. 2026 May 4;34(5):489. doi: 10.1007/s00520-026-10748-1.

ABSTRACT

PURPOSE: To evaluate the impact of telemedicine adoption and pandemic-related fear on treatment adherence, healthcare utilization, and supportive care processes among patients undergoing cancer therapy during the COVID-19 pandemic.

METHODS: In this prospective cohort study, we followed 149 cancer patients over two years to evaluate telemedicine utilization, treatment modifications, and COVID-19-related fear. We employed validated psychometric tools, including the COVID-19 Fear Scale.

RESULTS: Telemedicine adoption (24.8% of patients) was associated with fewer hospital visits (7.3 ± 3.2 vs 9.4 ± 4.1, p = 0.004) and reduced emergency room utilization (16.2% vs 46.4%, p < 0.001). Treatment modifications occurred in 55.9% of patients, predicted by COVID-19 infection (OR = 2.8, 95% CI:1.7-4.6) and neutropenia (OR = 2.1, 95% CI:1.3-3.4). High fear scores were linked to increased mortality (8.1% vs 2.7%, p = 0.032), disease progression (37.8% vs 21.4%, p = 0.018), lower treatment adherence (75.7% vs 87.5%, p = 0.041), and higher hospitalization rates (51.3% vs 24.1%, p < 0.001).

CONCLUSION: This study demonstrates that telemedicine can reduce acute care utilization while treatment modifications and high pandemic-related fear significantly worsen cancer outcomes. These findings highlight the need for oncology teams to proactively integrate remote care strategies and targeted psychological support to maintain treatment adherence and mitigate adverse outcomes during health crises.

PMID:42081154 | DOI:10.1007/s00520-026-10748-1

J Mol Histol. 2026 May 4;57(3):157. doi: 10.1007/s10735-026-10819-x.

ABSTRACT

A histological safety profile is essential for non-antibiotic microbial interventions in aquaculture. This study assessed the multi-organ histological biocompatibility of a novel actinobacterial strain, Agrococcus sp. RKDAS_1, in Nile tilapia (Oreochromis niloticus) under controlled conditions. Juvenile tilapia were fed diets with varying concentrations of RKDAS_1 (10⁵, 10⁷, and 10⁹ CFU g^{– 1} feed) for 60 days. Tissues from the gill, intestine, liver, and heart were analysed through standard histological methods, employing semiquantitative scoring and intestinal morphometry. Across all examined organs, RKDAS_1 supplementation did not induce inflammatory responses, degenerative lesions, or structural disruptions, which are indicative of tissue-level toxicity. Gill architecture was intact, with normal hepatocyte arrangements and no necrosis or fibrosis, while cardiac tissues showed a normal structure. Intestinal morphology maintained epithelial integrity, displaying dose-related variations in villus height and goblet cell density. Intermediate-dose live hepatic sections showed reduced cytoplasmic vacuolation compared to controls, though the difference was not statistically significant. The semi-quantitative histopathological evaluation showed that the tissue structure remained intact across different treatments. The results collectively suggest that Agrococcus sp. RKDAS_1 did not cause any noticeable histopathological damage, indicating enhanced biocompatibility. The findings suggest that Agrococcus sp. RKDAS_1 is compatible with biological tissues without causing significant damage. However, these conclusions are restricted to structural analysis and do not ensure functional improvements or overall safety beyond tissue examination. The findings provide a critical starting point for future research, which will delve into molecular, immunological, and long-term exposure studies. These investigations aim to evaluate the biotherapeutic potential of RKDAS_1 thoroughly.

PMID:42081141 | DOI:10.1007/s10735-026-10819-x

Pediatr Surg Int. 2026 May 4;42(1):213. doi: 10.1007/s00383-026-06455-x.

ABSTRACT

PURPOSE: Implementation of Enhanced Recovery After Surgery (ERAS) protocols in paediatric surgery remains limited, despite proven benefits in adults. The barriers to implementation and protocol modifications requires comprehensive detailing in paediatrics. We aimed to determine the practicality and safety of ERAS in paediatric laparoscopies at a tertiary-care center, addressing the context-specific barriers.

METHODS: This was a prospective, single-arm, preliminary study. One hundred thirty-six children, aged 2-14 years, undergoing laparoscopy were enrolled. ERAS elements were implemented perioperatively. The outcomes analysed included protocol compliance, length of hospital stay (LOS), 30-day complications, readmission and mortality rates. The challenges to implementation were noted.

RESULTS: Overall protocol compliance was 82.5 ± 12.4%. There was a significant correlation between adherence to components and LOS (r=-0.642 ; p < 0.01). Time to start liquids/solids and drain removal showed a significant correlation with LOS. No complications and 30-day readmissions were directly attributable to the fast-track concepts. There was no mortality. Key challenges included infrastructure, parental anxiety regarding early discharge and persistently motivating stakeholders to adhere the protocol.

CONCLUSION: Implementing paediatric ERAS protocol is safe and feasible within a tertiary health-setting. A high degree of multidisciplinary commitment can successfully overcome the unique logistic and cultural barriers with an accelerated convalescence.

PMID:42081132 | DOI:10.1007/s00383-026-06455-x