Category: Statistics

Mol Brain. 2025 Dec 5;18(1):90. doi: 10.1186/s13041-025-01258-y.

ABSTRACT

The glymphatic system plays a key role in brain waste clearance, but its genetic regulation remains poorly understood. Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index is a non-invasive imaging biomarker to asses glymphatic system activity. We integrated mean DTI-ALPS genome-wide association study (GWAS) data from 31,021 individuals of European ancestry with GTEx v8 multi-tissue eQTL data to perform transcriptome-wide association studies (TWAS) using Unified Test for Molecular Signature (UTMOST) and Functional Summary-based Imputation (FUSION). Gene-level associations were further validated by Multi-marker Analysis of Genomic Annotation (MAGMA). Causal inference was conducted using cis-Mendelian randomization (cis-MR) and summary-data-based Mendelian randomization (SMR), while colocalization was applied to provide evidence of strong associations between two traits within a single genetic region, thereby ensuring the stability of the MR conclusions. TWAS identified 17 candidate genes (AGBL5-IT1, CENPA, CGREF1, DNAJC5G, EMILIN1, GCAT, KHK, MAPRE3, OTOF, PLCL1, PREB, RBM43, RFTN2, SERPIND1, SNAP29, TRIOBP, and UCN), among which six protein-coding genes (TRIOBP, MAPRE3, EMILIN1, KHK, GCAT, and CGREF1) were further validated by MAGMA. Cis-MR provided evidence for the causal effects of these six genes, while colocalization supported that the MR conclusions were stable for four of them (TRIOBP, MAPRE3, EMILIN1, and GCAT). Finally, SMR identified three genes (TRIOBP, GCAT, and MAPRE3) that showed consistent and robust associations with DTI-ALPS across multiple tissues. These findings provide statistical evidence for genetic regulation of glymphatic function.

PMID:41351017 | DOI:10.1186/s13041-025-01258-y

Eur J Med Res. 2025 Dec 5. doi: 10.1186/s40001-025-03597-x. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in adults. While cyclophosphamide and cyclosporine are established treatments, rituximab has emerged as a promising alternative. This meta-analysis aims to compare the efficacy of rituximab versus cyclophosphamide and cyclosporine in patients with IMN.

METHODS: A meta-analysis was conducted in accordance with PRISMA guidelines. Databases including PubMed, EMBASE, Cochrane and Web of Science were searched for randomized controlled trials and observational studies comparing rituximab to cyclophosphamide or cyclosporine in adults with biopsy-confirmed IMN. The primary outcome was treatment efficacy (complete or partial remission). Risk of bias was assessed using the Cochrane RoB 2.0 tool. A random-effects model was used for pooling risk ratios. P < 0.05 was considered statistically significant. R software (4.5.0) was used to perform statistical analysis.

RESULTS: A total of eight studies comprising 936 patients were included in the meta-analysis. Rituximab was compared with cyclophosphamide or cyclosporine in idiopathic membranous nephropathy. The overall pooled analysis showed no significant difference in efficacy between treatment groups (RR = 1.117, 95% CI 0.882-1.414, P = 0.3595). Sensitivity analysis confirmed the robustness of the results. Subgroup analysis revealed that rituximab was more effective than cyclosporine in Asian populations, but less effective than cyclophosphamide in patients with severe renal dysfunction. No significant difference in severe adverse events (RR = 0.984, 95% CI 0.744-1.302, P > 0.05) was found between treatments.

CONCLUSION: Rituximab is comparable in efficacy to cyclophosphamide and cyclosporine for IMN treatment, with no significant difference in remission rates or severe adverse events. Treatment should be individualized.

PMID:41351015 | DOI:10.1186/s40001-025-03597-x

BMC Oral Health. 2025 Dec 6. doi: 10.1186/s12903-025-07463-4. Online ahead of print.

ABSTRACT

OBJECTIVES: Panoramic radiographs of twin and non-twin pediatric patients were analyzed to determine the prevalence of developmental dental anomalies. The concordance between monozygotic (MZ) and dizygotic (DZ) twin pairs was assessed to investigate the relative contributions of genetic and environmental factors to these anomalies.

MATERIALS AND METHODS: Panoramic radiographs from 419 pairs of twins and 838 non-twin patients, aged 7 to 13 years, who attended the clinic between 2017 and 2023, were examined for developmental dental anomalies. These anomalies were classified by number, size, shape, and positional anomalies. Categorical data were analyzed using the chi-square test, and the concordance of anomalies within twin pairs was evaluated using pairwise concordance and tetrachoric correlation analyses.

RESULTS: Developmental dental anomalies were observed in 33.2% of the twin group, 23.3% of the control group, 31.4% of the MZ twin group, and 33.8% of the DZ twin group. A statistically significant difference was identified in the prevalence of number anomalies between the twin and control groups (p = 0.025), whereas no significant differences were found for size, shape, and positional anomalies between these groups (p > 0.05). Analysis of MZ twin pairs revealed statistically significant concordance and tetrachoric correlation for anomalies such as hypodontia, dens invaginatus, taurodontism, impacted teeth, and infraoccluded primary molars.

CONCLUSION: The findings of our study indicate that genetic factors play a more significant role in the etiology of hypodontia, taurodontism, impacted teeth, and infraoccluded primary molars.

CLINICAL RELEVANCE: These findings present novel targets for future research aimed at elucidating the genetic and environmental determinants underlying developmental dental anomalies.

PMID:41351006 | DOI:10.1186/s12903-025-07463-4

Cardiovasc Diabetol. 2025 Dec 5;24(1):454. doi: 10.1186/s12933-025-03014-x.

ABSTRACT

BACKGROUND: The mechanisms underlying cardiorenal benefits of finerenone remain unclear. This mechanistic trial aimed to evaluate the effects of finerenone on vascular stiffness, as assessed using the cardio-ankle vascular index (CAVI), and cardiorenal biomarkers in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).

METHODS: Eligible patients with T2D and CKD (estimated glomerular filtration rate [eGFR], 25 to < 90 mL/min/1.73 m²; urinary albumin-to-creatinine ratio [UACR], 30 to < 3500 mg/g Cr) were randomly allocated to receive either dose-adjusted finerenone or matching placebo. The primary endpoint was the change in CAVI at week 24. The key secondary endpoint was the proportional change in UACR from baseline over 24 weeks. As an exploratory analysis, changes in circulating proteins were measured by using the Olink® Target 96 Cardiovascular III and Inflammation panels.

RESULTS: This investigator-initiated, multicentre, prospective, two-arm parallel, placebo-controlled, double-blind, randomised clinical trial was conducted at 13 sites in Japan. Among 102 patients randomised, 101 (66.3% men; median age, 73 years; eGFR, 56.2 mL/min/1.73 m²; and UACR, 193.8 mg/g Cr) were analysed. Changes in CAVI at week 24 were – 0.023 (95% confidence interval [CI], – 0.299 to 0.254) for finerenone and 0.011 (95% CI, – 0.245 to 0.267) for placebo. The group difference was – 0.057 (95% CI, – 0.428 to 0.314; P = 0.760). Compared with placebo, finerenone led to a 29% reduction in UACR levels at weeks 12 (group ratio 0.706 [95% CI, 0.504 to 0.989; P = 0.043]) and 24 (0.709 [95% CI, 0.506 to 0.994; P = 0.046]). Finerenone also resulted in an early and sustained eGFR decline over 24 weeks, without increasing levels of urinary biomarkers of acute tubular injury. Finerenone, compared with placebo, was associated with nominal changes in the expression of 11 proteins among the 181 circulating proteins tested.

CONCLUSIONS: Finerenone did not affect changes in vascular stiffness but led to a significant and sustained reduction in albuminuria in patients with T2D and CKD. The clinical benefits of finerenone may result from lowering intraglomerular pressure rather than from its effect on vascular stiffness.

REGISTRATION: ClinicalTrial.gov (NCT05887817) and Japan Registry of Clinical Trials (jRCTs021230011).

PMID:41351003 | DOI:10.1186/s12933-025-03014-x

BMC Public Health. 2025 Dec 5;25(1):4222. doi: 10.1186/s12889-025-25301-8.

ABSTRACT

BACKGROUND: Diarrhea remains one of the biggest public health threats in Ghana, and it is the most common cause of both morbidity and mortality among children in sub-Sahara Africa. Several preventive and adaptative public health measures such as Rota Virus vaccination and improving access to potable water are being implemented. There is little research in Ghana examining the climatic resilience of these preventative and adaptive interventions. The study aimed at determining whether the preventative and adaptive interventions are climate-resilient by using morbidity data.

METHODS: In this research, time series data of monthly all-cause diarrhea morbidity, rainfall, temperature, and relative humidity which span the period of January 2014 to December 2020 were analyzed. The study used the Auto Regression Distributed Lag cointegration approach to model the impact of the climatic variables on all-cause diarrheal morbidity.

RESULTS: Public health preventative and adaptation strategies are climate robust and unresponsive to changes in climatic variables. The residuals in the models estimated are white noise and do not exhibit serial autocorrelation or conditional heteroscedasticity.

CONCLUSION: In the Tamale Metropolitan Area, climate change has no effect on diarrhea morbidity, supporting the claim that climate resilience is an important component of public health preventive interventions against diarrhea. The study findings as a whole emphasize the significance of climate-sensitive, evidence-based public health strategies.

PMID:41351001 | DOI:10.1186/s12889-025-25301-8

BMC Oral Health. 2025 Dec 5. doi: 10.1186/s12903-025-07052-5. Online ahead of print.

ABSTRACT

BACKGROUND: Dental trauma constitutes the second most common cause of emergency dental care worldwide, after cavities, accounting for approximately 5% of all physical injuries across all age groups. Early intervention is crucial, especially for children and adolescents, who present a higher incidence due to their active lifestyle. This study aims to conduct a systematic review and descriptive analysis to assess the level of knowledge among non-dental healthcare professionals in the management of dental trauma, identifying gaps in their education and proposing educational interventions to improve care in this critical field.

METHODS: This systematic review was structured according to the SPIDER strategy: population, non-dental healthcare professionals, exposure to a clinical situation, management of dental trauma and outcome knowledge, attitude and awareness. The included studies were analyzed descriptively. Mean values and other summary statistics reported in each study were extracted and organized according to the primary variables of interest, focusing on the domains of knowledge, attitudes, and practices of non-dental healthcare professionals. Due to the substantial heterogeneity in study designs, measurement tools, and response formats, no pooled or inferential analyses were performed. The articles were analyzed by the authors and summarized using a “KAP Heat Map” approach, in which colors indicated the level of knowledge (< 25%, 25-50%, 51-75%, and > 75%), and the width of the columns represented the number of studies for each question stem (QS), based on data reported in the included studies.

RESULTS: Only two studies of 25 concluded that the level of knowledge was adequate, seven studies indicated a moderate level of knowledge, and sixteen studies reported an inadequate level of knowledge. Twelve of the included studies mention the need for continuing education in dental trauma for health professionals. Most included studies exhibited moderate to high risk of bias.

CONCLUSIONS: The studies reviewed showed that the level of knowledge of health professionals such as doctors and nurses is inadequate. This shows a lack of training during their academic training as well as a lack of training in the workplace.

TRIAL REGISTRATION: This systematic review has been registered in PROSPERO with CD CRD578189 on August 9, 2024.

PMID:41351000 | DOI:10.1186/s12903-025-07052-5

BMC Infect Dis. 2025 Dec 6. doi: 10.1186/s12879-025-11747-z. Online ahead of print.

ABSTRACT

BACKGROUND: Aminoglycoside pharmacokinetics is expected to change in premature infant. However, the PK profile of amikacin in Chinese premature infants has not been characterized. The aim of this study was to assess the safety and describe the pharmacokinetics properties of amikacin in Chinese premature infants.

METHODS: This was a two-center, retrospective, pharmacokinetic study. Phoenix NLME was used to construct a pharmacokinetics model. Monte Carlo simulations were performed to screen the optimal dosage regimen.

RESULTS: A total of 54 amikacin concentrations from 23 patients were available for population pharmacokinetic analysis. The patients received an amikacin total daily dose (median(range)) of 14.32 (10.34-19.70) mg/kg. The distribution of C_min (median(range)) was 4.07 (1.01-30.99)µg/mL, and C_max (median(range)) was 17.45 (4.56-164.72) µg/mL. There were 14 patients achieved target C_min, and 6 infants achieved C_max. There were 3 cases occurred acute kidney injury, with C_max and C_min all exceeded the recommended range. A one-compartment model with first-order elimination best described the amikacin concentration-time data. The estimated typical values of clearance and volume of distribution for amikacin were 1.43 L/h/70kg and 30.97 L/70kg, respectively. Covariate analyses revealed that statistically significant relationships between amikacin clearance and weight, postmenstrual age and renal function, while there was a statistically significant relationship between volume of distribution and weight. Based on the model-based simulations, the initial recommend dosage regimens prior to therapeutic drug monitoring were suggested as 13 mg/kg q24h, 12 mg/kg q36h and q48h for serum creatinine between 15-22µmol/L; 23-36 and 37-60µmol/L, respectively.

CONCLUSION: Weight, postmenstrual age and renal function have significant influence on the PK of amikacin in Chinese premature infants. The optimal dosage regimens might provide an alternative choice for premature infants in China in the therapy of amikacin.

PMID:41350991 | DOI:10.1186/s12879-025-11747-z

BMC Geriatr. 2025 Dec 5;25(1):999. doi: 10.1186/s12877-025-06685-z.

ABSTRACT

BACKGROUND: As the number of older people living at home increases, the role of home care services (HCS) becomes more important. Diabetes is associated with premature mortality and is common among older people in HCS, yet mortality patterns among HCS recipients are not well known. This study aimed to estimate all-cause and cause-specific mortality risk in persons with pharmacologically treated diabetes receiving HCS compared to other HCS recipients and explore whether mortality risk differed between diabetes treatment subgroups.

METHODS: This nationwide registry study merged data from the Norwegian Information System for the Nursing and Care Sector with data from the Norwegian Prescription Database, the Norwegian Patient Registry, and the Cause of Death Registry (CDR). The study population included recipients of HCS (aged 65-90 years at baseline) in Norway between 2009 and 2014. Individuals were classified as having pharmacologically treated diabetes (hereafter referred to as diabetes) (≥ 1 prescription of glucose-lowering drugs (GLD) in the current half year or the year before), or not having diabetes. Those with diabetes were further sub-classified into “non-insulin GLD only”, “insulin and non-insulin GLD”, or “insulin only”. Time of death and the underlying cause of death were retrieved from CDR. The study population, diabetes status, covariates, and all-cause mortality were updated each half-year. Mortality risk was compared between groups using Cox proportional hazards regression, with age as time scale, and reported as hazard ratio (HR) with 95% CIs.

RESULTS: Women in the “insulin only” group had a higher risk of all-cause mortality (HR 1.18 (CI 1.11-1.25)) than women without diabetes, while in the “non-insulin GLD only” and “insulin and non-insulin GLD” subgroups, both women and men with diabetes had lower mortality risks than those without diabetes. Overall, persons with diabetes had a higher risk of cardiovascular mortality (HR 1.23 (CI 1.19-1.28)) compared to persons without diabetes, and a lower risk of dying from cancer (HR 0.68 (CI 0.66-0.70)) and respiratory disease (HR 0.67 (CI 0.62-0.72)).

CONCLUSION: Mortality risk varied by diabetes status and treatment subgroups. Most diabetes subgroups had lower all-cause mortality risk than those without diabetes, except for women using “insulin only”, underscoring the need for individualized HCS.

PMID:41350985 | DOI:10.1186/s12877-025-06685-z

BMC Geriatr. 2025 Dec 5;25(1):1000. doi: 10.1186/s12877-025-06620-2.

ABSTRACT

BACKGROUND/OBJECTIVE: The relationship between frailty and sarcopenia is well-known in older adults, but the factors associated with frailty were not adequately investigated. This study aimed to investigate the relationship between frailty levels and balance, fall risk, and kinesiophobia in older adults with primary sarcopenia and to compare them by sex.

METHODS: This cross-sectional study included 68 (32 female, mean age 71.56 ± 5.04 years; 36 male, mean age 71.97 ± 4.86 years) older adults with primary sarcopenia. Sarcopenia was assessed based on grip strength, skeletal muscle mass, and physical performance. Frailty levels (Edmonton Frailty Scale (EFS)), dynamic and static balance (Force plate), fall risk (Denn Fall Risk Assessment Scale), and kinesiophobia (Tampa Kinesiophobia Scale (TSK)) of the individuals were assessed.

RESULTS: Sarcopenic females had statistically significantly higher levels of frailty, fall risk, kinesiophobia, and decreased balance stability areas than males (p < 0.05). The prevalence of frailty among older adults with sarcopenia was 51.5%, with a mean EFS score of 6.54 ± 2.51. Females had significantly higher frailty levels than males (7.53 ± 2.81 vs. 5.67 ± 1.83, p = 0.002). Fall risk was also higher in females (10.66 ± 5.83 vs. 7.17 ± 4.29, p = 0.007), as was kinesiophobia (47.59 ± 6.37 vs. 41.81 ± 5.09, p < 0.001). Frailty showed a moderate positive correlation with fall risk (r = 0.603, p < 0.001) and kinesiophobia (r = 0.510, p < 0.001), and a weak negative correlation with balance stability in the anterior direction (r=-0.249, p = 0.040) and to the right (r=-0.265, p = 0.030).

CONCLUSION: Sarcopenic females have higher levels of frailty and have a higher risk of falling and kinesiophobia than males. Sarcopenic females also have more impaired balance. Increased frailty levels in older sarcopenic adults are associated with increased fear of falling and kinesiophobia, and impaired balance. Therefore, assessment of frailty and associated factors in older adults with sarcopenia is essential in planning rehabilitation.

PMID:41350982 | DOI:10.1186/s12877-025-06620-2

BMC Anesthesiol. 2025 Dec 5. doi: 10.1186/s12871-025-03532-x. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of this study is to compare the effects of remimazolam and dexmedetomidine on the incidence of hypotension in middle-aged and elderly patients undergoing general anesthesia, and to evaluate the safety profiles of both medications.

METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, and Web of Science from inception to July 2024 for randomized controlled trials comparing remimazolam versus dexmedetomidine in patients aged ≥ 45 years undergoing general anesthesia. Two investigators independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Meta-analyses employed random-effects models to calculate risk ratios (RR) with 95% confidence intervals. The primary outcome was intraoperative hypotension incidence; secondary outcomes included bradycardia, tachycardia, hypertension, and postoperative nausea and vomiting.

RESULTS: This meta-analysis included 8 randomized controlled trials with 741 patients (384 remimazolam; 357 dexmedetomidine). There was no statistically significant difference in intraoperative hypotension between groups (RR 0.78, 95% CI 0.36-1.68, P = 0.53, I²=71%). Remimazolam showed a significant reduction in bradycardia risk compared to dexmedetomidine (RR 0.41, 95% CI 0.23-0.73, P = 0.002, I²=0%). However, remimazolam had a higher risk of tachycardia (RR 3.41, 95% CI 1.47-7.90, P = 0.004, I²=0%). There was no significant difference in intraoperative hypertension (RR 0.85, 95% CI 0.38-1.90, P = 0.69, I²=0%) or postoperative nausea and vomiting(RR 0.98, 95% CI 0.30-3.23, P = 0.97, I²=0%).

CONCLUSIONS: Remimazolam and dexmedetomidine did not differ significantly in intraoperative hypotension, intraoperative hypertension, or postoperative nausea and vomiting in middle-aged and elderly patients. Remimazolam reduced the incidence of bradycardia. In contrast, dexmedetomidine had an advantage in reducing intraoperative tachycardia. These findings support individualized anesthetic selection based on patients’ specific cardiovascular risk profiles.

PMID:41350976 | DOI:10.1186/s12871-025-03532-x