Nevin Manimala

BMC Endocr Disord. 2025 Nov 14;25(1):264. doi: 10.1186/s12902-025-02087-9.

ABSTRACT

BACKGROUND: As type 2 diabetes mellitus (T2DM) has emerged as a global health challenge, various treatment strategies, such as the use of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors, have been widely adopted. However, evidence on the effectiveness of their combination therapy remains limited, particularly in studies utilizing target trial emulation approaches within the South Korean population.

METHODS: This emulated target trial included 68,372 patients with T2DM identified between 2001 and 2024 from four university hospitals in South Korea. After applying exclusion criteria, patients were classified into two groups: metformin monotherapy and metformin plus alogliptin dual therapy. A 1:2 propensity score matching approach was used to balance baseline covariates between groups. The outcome of this analysis was the achievement of glycemic control, defined as haemoglobin A1c (HbA1c) < 6.5% during the follow-up period. Clinical parameters, including glycemic indices, were assessed over 24 weeks from the initiation of therapy using unpaired t-tests. Cox proportional hazards models were employed to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) to evaluate the likelihood of achieving glycemic control.

RESULTS: After applying exclusion criteria and performing 1:2 propensity score matching, 1230 patients were included in the final analysis (371 in the dual therapy group and 662 in the monotherapy group). Over the 24-week follow-up period, the dual therapy group showed greater reductions in HbA1c and fasting plasma glucose, with the greatest improvement observed at 8 weeks. No significant differences were found between groups in changes across other clinical parameters. Although the reduction in HbA1c during 24-week follow-up period was greater in the dual therapy group, the difference did not reach statistical significance. However, over the extended follow-up period, patients receiving dual therapy exhibited a higher likelihood of achieving glycemic control (HbA1c < 6.5%) compared to those on monotherapy (aHR, 2.41; 95% CI, 1.64-3.55).

CONCLUSION: By emulating a target trial, this study showed that dual therapy with metformin and alogliptin improved glycemic control in patients with T2DM in South Korea. Given the growing number of available treatment regimens, future research should incorporate a wider range of antidiabetic agents and explore the effectiveness of various therapeutic combinations.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41239448 | DOI:10.1186/s12902-025-02087-9

Arch Public Health. 2025 Nov 14;83(1):277. doi: 10.1186/s13690-025-01751-9.

NO ABSTRACT

PMID:41239445 | DOI:10.1186/s13690-025-01751-9

Clin Epigenetics. 2025 Nov 14;17(1):190. doi: 10.1186/s13148-025-02007-7.

ABSTRACT

BACKGROUND: Polypharmacy, defined as taking ≥ 5 different daily medications, is common in older adults and has been linked with neuropsychiatric/neurological and other health conditions. To clarify the potential molecular implications, we tested the hypothesis that polypharmacy may influence DNA methylation (DNAm) patterns in aging, in a longitudinal Italian cohort (N = 1,098; mean (SD) age at recruitment: 58.8 (5.6) years, 51.3% women; median (IQR) follow-up 12.6 (1.1) years).

RESULTS: We tested associations of polypharmacy with several DNAm aging clocks (Hannum, Horvath, GrimAge, DNAmPhenoAge, DunedinPACE), through linear mixed models incrementally adjusted for age, sex, education, prevalent health conditions and lifestyles, leukocyte counts and residual batch effects. This revealed significant positive associations of GrimAge acceleration and DunedinPACE with the switch to polypharmacy status during follow-up (Beta (SE): 0.024 (0.008) and0.0012 (0.0004)). While the association of GrimAge was driven by a DNAm-based surrogate of tissue inhibitor metalloproteinase 1 (TIMP-1), no significant association was detected for component CpGs of DunedinPACE. When we tested associations of polypharmacy with 668,413 CpGs epigenome-wide, we observed no statistically significant findings (top hit: cg07675998; chr11q13.1; Beta (SE) = 0.009 (0.002); p = 1.5 × 10^-6). However, these showed significant enrichments of several biological functions and pathways related to renal tissue, lipoproteins, inflammatory and immune response.

CONCLUSIONS: These findings suggest an influence of polypharmacy on accelerated epigenetic aging and on altered methylation patterns in the genome, suggesting a potential implication of pathways related to renal tissue development, lipoproteins and cholesterol homeostasis, inflammatory and immune response, in line with previous proteomic analyses of polypharmacy mouse models. These observations also suggest potential targets for mitigating disruptive effects of polypharmacy on elderly health.

PMID:41239444 | DOI:10.1186/s13148-025-02007-7

Malar J. 2025 Nov 14;24(1):399. doi: 10.1186/s12936-025-05645-7.

ABSTRACT

BACKGROUND: Ghana still faces prevailing malaria cases despite the progress made in reducing its incidence. The formal private drug retail sector most at times tends to be the first source of healthcare for people with fever. However, there is limited information from this sector with regards to the documentation and reporting of malaria cases and other diseases. This study examined malaria documentation and reporting practices among formal drug retail shops in the Hohoe Municipality as part of efforts to enhance tracking of malaria.

METHODS: A concurrent mixed-methods approach was employed, comprising a cross-sectional study of 57 formal drug retail facilities (9 from Community Pharmacies and 48 from Over-the-Counter Medicine Sellers [OTCMS]) and an exploration study of 7 of them. Quantitative data was collected via semi-structured questionnaires and analysed using Stata. The quantitative data was analysed using descriptive (frequencies and proportions) and bivariate (fishers’ exact test) analysis. Statistical significance was measured at a p-value of 0.05. Qualitative data from 7 in-depth interviews were thematically analysed using ATLAS.ti to identify key themes.

RESULTS: The median age of the participants was 26 years (IQR = 24-42), with 40 (70.2%) qualified as Counter Medicine Assistants, and 38 (66.7%) having 1-5 years of work experience. Of the 57 shops, 51 (89.5%) lacked documentation and reporting tools; only 5 (10.5%) used paper-based methods with significant differences observed between community pharmacies and OTCMS (p = 0.004). Digital reporting was favoured by 35 (61.4%) of attendants, prioritizing a user-friendly interface, data security, and real-time data submission. Participants highlighted barriers like stress and resource constraints but suggested solutions such as improved staffing, training, and digital infrastructure.

CONCLUSIONS: Malaria documentation and reporting were low, with few facilities relying on paper-based methods. Digital reporting was preferred but faces challenges like resource constraints and inadequate training. Addressing these barriers through infrastructure investments and comprehensive training with collaborations between the National Malaria Elimination Programme (NMEP) and the Ghana Pharmaceuticals Council (GPC) will improve data accuracy and reporting, even in low-connectivity areas.

PMID:41239439 | DOI:10.1186/s12936-025-05645-7

Neurol Res Pract. 2025 Nov 14;7(1):88. doi: 10.1186/s42466-025-00450-8.

ABSTRACT

BACKGROUND: Despite current guidelines recommending against intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with direct oral anticoagulants (DOAC) within prior 48 h, latest real-world data indicate no increased bleeding risk. However, these observations are based mainly on alteplase (rt-PA), whereas data for tenecteplase (TNK) are scarce.

METHODS: We retrospectively compared data from our stroke registry of AIS-patients with DOAC (intake within the last 48 h), who received IVT either with rt-PA or TNK without prior antagonization. The primary outcome was the rate of symptomatic intracranial hemorrhage (sICH) per SITS-Most criteria. Secondary outcomes included the rate of any ICH or major bleeding, rate of mortality, neurological and functional outcome at discharge.

RESULTS: 82 AIS-patients were included, with 42 patients receiving TNK und 40 patients receiving rt-PA. Median age was 83 y for TNK patients and 82 y for rt-PA patients. Median NIHSS score at admission for TNK was 9 points for both groups (p = 0.61). Median drug-specific DOAC plasma level was 49 ng/mL for TNK versus 24 ng/mL for rt-PA (p = 0.04). We found no statistically significant increased risk for neither sICH (TNK 2.4% vs. rt-PA 2.5%; p = 1), nor for other safety outcomes for TNK-treated patients compared with rt-PA. The rate of excellent functional outcome (TNK 61.9% vs. rt-PA 52.5%) was similar among both groups. High drug-specific DOAC plasma levels were not related to an increased rate of hemorrhagic complications in our cohort.

CONCLUSION: We report no increased rate of (s)ICH for TNK based IVT compared with rt-PA in AIS-patients with DOAC, indicating a similar safety profile. Moderate to high drug-specific DOAC levels were no surrogates for hemorrhagic complications, supporting the implementation of specific Standard Operating Procedures for IVT in DOAC-treated patients. Contrary to previous studies, we did not observe an increased rate of early recanalization of LVO in TNK-treated patients in this small single-center cohort.

TRIAL REGISTRATION: n/A.

PMID:41239434 | DOI:10.1186/s42466-025-00450-8

Neurol Res Pract. 2025 Nov 14;7(1):89. doi: 10.1186/s42466-025-00448-2.

ABSTRACT

BACKGROUND AND AIMS: Stroke remains a leading cause of mortality and disability in many low- and middle-income countries, where access to diagnostic and treatment resources is often severely constrained. This pilot study investigated the feasibility of telemedicine-based training to integrate carotid artery ultrasound and Holter monitoring into routine diagnostic practices at the stroke unit of the University Teaching Hospital (UTH) in Lusaka, Zambia.

METHODS: Five neurology residents at the University Teaching Hospital in Zambia, without prior clinical experience in carotid artery ultrasound, received remote online training sessions. Subsequently, they were divided into two groups: the first conducted practical examination sessions under on-site supervision of a stroke neurologist, while the second was remotely supervised via screen sharing by a stroke neurologist from Krankenhaus Nordwest in Frankfurt (KHNW), Germany. Handheld portable ultrasound probes (Butterfly IQ+) were used for the examinations. Following the training, each group of residents performed 50 extracranial ultrasound examinations in acute ischemic stroke patients at the UTH stroke unit. Each examined patient was re-examined in a separate session by an experienced stroke neurologist, who was blinded to the results of the residents’ examination. The agreement between raters in the assessment of carotid stenosis was assessed using Cohen’s kappa (κ), a statistical measure that evaluates interrater reliability for categorical items. Similarly, 26 stroke nurses at UTH were trained in Holter monitoring exclusively through video tutorials, without hands-on practice. They recorded 30 Holter examinations on subsequent acute ischemic stroke patients. The quality of the recordings was subsequently compared to 30 Holter recordings from consecutive patients at the stroke unit of KHNW. A cardiologist, blinded to the origin of the recordings, evaluated their quality on a scale of 1 to 10, and the results were analyzed using Welch’s t-test. All participants completed multiple-choice assessments to evaluate their theoretical knowledge, along with a feedback survey on the training program.

RESULTS: 50 patients underwent bilateral carotid artery ultrasound examination, split evenly between the direct and remotely supervised groups. Both groups achieved a high rate of concordance with an experienced stroke neurologist. The directly supervised group achieved 86% concordance for ICA stenosis and 88% for plaque detection, while the remotely supervised group achieved 80% and 84%, respectively. Holter recordings from UTH demonstrated higher quality than those from the stroke unit at KHNW (p < 0.01). Most participants reported enhanced confidence and knowledge, though over 60% preferred face-to-face training formats.

CONCLUSION: Innovative telemedical training approaches offer a transformative solution for addressing diagnostic and infrastructure challenges in stroke care, particularly in resource-constrained healthcare settings. Comprehensive research is crucial to optimize these programs and enhance medical capabilities across diverse healthcare environments.

PMID:41239430 | DOI:10.1186/s42466-025-00448-2

BMC Med Educ. 2025 Nov 14;25(1):1604. doi: 10.1186/s12909-025-08009-6.

ABSTRACT

BACKGROUND: Physician Assistant/Associate (PA) students are facing increased impairment, adverse academic experiences, and impeded performance. Despite well-documented research demonstrating the multi-factorial wellness needs of many PA students nationally, the unnecessary challenges and continuance of harm persists. Such barriers have influenced student performance, stability, outcomes, and undesirable health events. Further, evidence suggests that student learner wellness is influenced by predisposing and mitigatable factors, which can be addressed proactively at the individual and program level. Early identification of well-being needs, risk factors, and modifiable action steps can enhance student success during the intensive educational journey of the PA student pre-clinical workforce. Therefore, examining, optimizing, and integrating longitudinal wellness practices across curricular design and program operations can have a lasting impact on learners, including as the future healthcare workforce (HCW). This scoping review aims to investigate wellness practices, alignment of their terminologies and implementations for PA students in the United States (U.S.) and evaluate health profession programs’ implications of the future HCW.

METHODS: The authors utilized a Joanna Briggs Institute (JBI) scoping review protocol and logic model to investigate the research query. Literature retrieval was led by the research librarian using keywords, Boolean operators, and database-specific terminology. Using a population, intervention, comparison, outcome, and setting (PICOS) framework and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) tools, studies were vetted through a phased eligibility screening process according to inclusion/exclusion criteria (PA students, wellness practices, occurred within the U.S., original research). Data extraction occurred systematically and involved categorization of terminology (constructs, positive/negative tone), wellness practices, and student impact and outcomes. Findings were mapped to best-fit wellness dimensions using the National Wellness Institute (NWI) competency-based model and to the PA Core Competencies. Thematic and directed content analysis was performed in sequence to determine culminative study results.

RESULTS: A total of 447 studies were retrieved from database searching (n = 439) and handsearching (n = 8). After initial screening and full-text review, 25 studies met inclusion criteria for a total of 9,628 PA student participants. Out of the 25 studies examined, 13/25 (52%) explored the didactic year, 3/25 (12%) examined the clinical year, 7/25 (28%) studied both, and 2/25 (8%) did not specify (Table 1). 28% (n = 7/25) of studies were anchored in evidence-based frameworks. Terminology, wellness practices, and implementation varied across the health professions programs. The ‘construct tone’ across studies used was nearly equivalent when examining positive (50.89%) versus negative (49.11%) terms related to ‘well-being,’ Three of 7 (42.86%) dimensions of wellness were most prevalent (EP, IM, and OA) (Fig. 2), whereas the remaining 4 of 7 (57.14%) dimensions (Ph, Sp, Soc, and OWB) had less representation (Table 2). Wellness practices were siloed or brief in nature as seen in 15/25 studies (60%), such as an isolated module or class session, and none of the studies (n = 0/25) addressed all the dimensions of wellness. Findings related to PA student positive/negative wellness experiences sourced directly from the included studies showed statistical significance (p < 0.0001 to p = 0.05), a predominance of moderate to strong correlations (r = -0.802, r = 0.762), and a range of effect sizes: odds ratios (1.04 to 2.09), Cohen’s d (0.09 to 0.38), and Pearson’s r (0.0 to 0.16).

CONCLUSIONS: Unified terminology, definitions, and implementation of wellness practices are necessary to optimize PA student success as future clinicians practicing medicine. Establishing and fostering practices that promote wellness habits, work-life balance, and modernization of antiquated health professions programs is an investment in the iterative growth toward long-term well-being, resilience, and success.

PMID:41239420 | DOI:10.1186/s12909-025-08009-6

J Health Popul Nutr. 2025 Nov 14;44(1):400. doi: 10.1186/s41043-025-01144-2.

ABSTRACT

BACKGROUND: Sarcopenia is a generalized skeletal muscle disease that significantly affects daily life and increases the risk of falls, fractures, and other related complications. Recent studies have shown that dietary adjustments can effectively prevent and delay the onset of sarcopenia.

METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 were used in this investigation. We employed weighted multivariable logistic regression models to investigate the relationship of eight dietary factors with sarcopenia, and further explored these associations using weighted restricted cubic splines (RCS) and subgroup analyses.

RESULTS: A total of 8,221 participants were included in the study, of whom 715 were diagnosed with sarcopenia. In the weighted multivariable logistic regression model (Model 2), after adjusting for confounding factors, a significant negative association was observed between the intake of macronutrients and the incidence of sarcopenia: energy (OR 0.19, 95% CI 0.11-0.34), protein (OR 0.38, 95% CI 0.26-0.55), dietary fiber (OR 0.50, 95% CI 0.34-0.73), carbohydrates (OR 0.57, 95% CI 0.38-0.85), total sugars (OR 0.61, 95% CI 0.42-0.89), total fat (OR 0.60, 95% CI 0.41-0.88), total saturated fatty acids (OR 0.59, 95% CI 0.40-0.88), and total cholesterol (OR 0.51, 95% CI 0.35-0.77). A substantial linear negative link in the occurrence of sarcopenia and these eight dietary factors was found using RCS analysis. Subgroup analyses further confirmed the robustness of the relationship between macronutrients and sarcopenia.

CONCLUSIONS: Increasing the intake of dietary fiber, protein, energy and fat, while appropriately managing carbohydrate and cholesterol intake, may help reduce the risk of sarcopenia.

PMID:41239412 | DOI:10.1186/s41043-025-01144-2

BMC Surg. 2025 Nov 14;25(1):545. doi: 10.1186/s12893-025-03207-x.

ABSTRACT

OBJECTIVES: To compare outcomes of nasogastric (NGT) or nasoenteric tube decompression against no decompression in the non-operative management of adhesional small bowel obstruction (ASBO) using a systematic review and meta-analysis.

METHODS: Database searches up to February 2025 were conducted using Cochrane Library, EMBASE, MEDLINE and SCOPUS. Abstract screening and data extraction were performed by two independent reviewers. Patients aged 18 and above were included. Studies were excluded if they compared NGTs to long tube devices or if the primary aetiology of SBO was not adhesions. Quality appraisal was conducted using the Newcastle Ottawa Scale and meta-analysis was performed using RevMan Web Software.

RESULTS: Searches yielded 1442 studies, of which 4 met the inclusion criteria, comprising a total of 1219 patients undergoing non-operative management for ASBO. These were all retrospective cohort studies. Within these studies, a total of 732 patients had a nasogastric or nasoenteric tube inserted for ASBO while 487 patients were managed without one. NGT use had a non-significant trend toward increased operative intervention, with a pooled odds ratio of 2.58 (95% CI: 0.77 to 8.65; p = 0.09, I² = 82%). Three studies compared bowel resection rates; NGT use was not associated with a statistically significant increased risk of bowel resection (OR 2.31; 95% CI: 0.86-6.16; p = 0.10). All studies reported a longer length of hospital stay in the NGT group.

CONCLUSIONS: The available evidence is sparse, limited in design and quality, and marked by high heterogeneity, making it insufficient to draw a definitive conclusion regarding the role of NGTs in ASBO. High-quality evidence from a randomised controlled trial is needed to guide future practice.

TRIAL REGISTRATION: PROSPERO (CRD: CRD42021256098).

PMID:41239407 | DOI:10.1186/s12893-025-03207-x

BMC Psychol. 2025 Nov 14;13(1):1263. doi: 10.1186/s40359-025-03611-1.

ABSTRACT

BACKGROUND: Previous studies have shown that family relationships are closely related to internet gaming disorder (IGD) in adolescents. There are also neurological mechanisms that correlate spontaneous brain activity with adolescent family relationships and IGD. Therefore, this study explores the mediating role of spontaneous brain activity between family relationships and IGD in adolescents.

METHODS: This study used a cross-sectional design. It recruited 52 IGD adolescents as the IGD group and 51 normal adolescents as the healthy control (HC) group. The study included adolescents aged 12-18 years, with a male-to-female ratio of 45:7 in the IGD group and 41:10 in the HC group. The diagnosis of IGD was established based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria. The Young Internet Addiction Scale (YIAS) was used to assess the severity of internet addiction among adolescents, and the Chinese version of the Family Environment Scale (FES-CV) was used to evaluate family relationships. Resting-state functional MRI was utilized to assess adolescents’ spontaneous brain activity, specifically measuring the mean amplitude of low-frequency fluctuation (mALFF) and functional connectivity (FC). MRI data were collected using a Siemens Magnetom Prisma 3.0T MRI scanner. The specific scan sequence and parameters are as follows: BOLD sequence, repetition time (TR) = 1000 ms, echo time (TE) = 30 ms, flip angle = 70°, slice thickness = 2.2 mm, number of slices = 52, matrix size = 64 × 64, voxel size = 3 mm × 3 mm × 3 mm, scan duration = 360 s. The steps of data preprocessing included data format conversion, exclusion of time points, slice timing correction, head motion correction, spatial normalization, removal of linear drift, regression of covariates, band-pass filtering, and data cleaning. Statistical analysis was conducted using SPSS 22.0. Gaussian random field (GRF) correction was applied in the DPABI toolbox, with voxel-level p < 0.005 and cluster-level p < 0.05 indicating statistical significance. Pearson correlation was employed to analyze the relationships between various scales and between these scales and brain spontaneous activity. Mediation analysis was performed using the SPSS Process program.

RESULTS: (1) Compared to the HC group, the IGD group had significantly higher YIAS scores (t = 21.571, P < 0.05). For the FES-CV scores, the IGD group scored higher in conflict (t = 4.228, P < 0.05) and lower in cohesion (t=-3.768, P < 0.05), with statistically significant differences. (2) Pearson correlation analysis revealed a negative correlation between cohesion in family relationships and middle frontal gyrus (MFG) (r = – 0.443, p < 0.01), a negative correlation between cohesion and internet addiction (r = – 0.474, p < 0.01), and a positive correlation between internet addiction and MFG (r = 0.557, p < 0.01) in the IGD group. The MFG mediated the relationship between family relationships and internet addiction, with a mediation effect value of -0.183 (95% CI=-0.403 ~ -0.037), accounting for 38.77% of the total effect (-0.183/-0.472). (3) In the IGD group, the FC value from the MFG to the right insula was positively correlated with conflict in family relationships (r = 0.349, P < 0.05).

CONCLUSION: Family relationships are related to internet addiction in adolescents, and the MFG mediates this relationship. Additionally, the FC value from the MFG to the right insula in the IGD group is positively correlated with conflict. This suggests that the MFG may serve as a neurobiological marker through which family relationships influence IGD development in adolescents.

PMID:41239403 | DOI:10.1186/s40359-025-03611-1