Nevin Manimala

Clin Pharmacokinet. 2026 May 26. doi: 10.1007/s40262-026-01637-1. Online ahead of print.

ABSTRACT

BACKGROUND: Mavyret, a combination medication of glecaprevir (GLE) and pibrentasvir (PIB), is approved to treat chronic and acute hepatitis C virus (HCV) (genotypes 1-6) infection in adults and pediatric patients ≥ 3 years old. To support approval, a two-part clinical trial was conducted in adolescents (≥ 12 to < 18 years) and children (≥ 3 to < 12 years) to identify the appropriate dosage and determine the efficacy and safety in pediatric patients.

OBJECTIVES: Population pharmacokinetic (popPK) analyses reported herein aimed to (1) characterize the pharmacokinetic (PK) parameters of orally administered GLE and PIB and the sources of PK variability in pediatric patients and (2) support the use of a body weight-based pediatric GLE/PIB dose ratio of 50/20 mg in HCV-infected children.

METHODS: PopPK models were built for GLE and PIB independently using nonlinear mixed-effects modeling and utilized data collected from 126 pediatric patients. Demographic, pathophysiological, and treatment factors were investigated for their impact on GLE and PIB PK.

RESULTS: PopPK analyses of pediatric exposures confirmed comparable exposures to those of adults who achieved over 95% sustained virologic response (SVR12). The pediatric popPK model incorporated allometric body weight-based scaling and subsequently identified no covariate that significantly impacted GLE exposures. Similarly, no covariate beyond the specified allometric body weight scaling was identified to impact PIB exposures. The developed pediatric popPK models were able to describe the central tendency and variability of the data.

CONCLUSION: These results supported the approval of body weight-based dosing regimens of GLE and PIB in children (< 45 kg) infected with any HCV genotype.

CLINICAL TRIALS: NCT03067129.

PMID:42189498 | DOI:10.1007/s40262-026-01637-1

Sports Med. 2026 May 26. doi: 10.1007/s40279-026-02448-x. Online ahead of print.

ABSTRACT

BACKGROUND: Sport-related concussion (SRC) is a common and complex injury in athletic populations. Linear head acceleration (LHA) and rotational head acceleration (RHA) are key biomechanical factors believed to contribute to SRC, each through distinct mechanisms. Evaluating head impact magnitudes across different sports, athlete populations, and measurement methods is essential for advancing SRC injury prevention and risk assessment.

OBJECTIVE: We aimed to examine linear and rotational head acceleration magnitudes associated with SRC impacts in athletes participating in team sports across all ages and both sexes.

METHODS: We conducted a systematic review and meta-analysis adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We searched three databases (MEDLINE, Scopus, SPORTDiscus) until 4 September, 2024, and the literature search was updated on the 10 November, 2025. Observational and experimental studies reporting peak LHA and/or RHA during SRC impacts in team sport athletes were included. Data were extracted on study characteristics, instrumentation, and head impact magnitudes. The risk of bias was assessed using the National Institutes of Health Quality Assessment Tool, and the certainty of the evidence was evaluated using GRADE. Random-effects meta-analyses were conducted to compare SRC and non-concussive impacts, and subgroup analyses were performed by sport type, age group, sex, session type, and instrumentation type, reporting standardized mean difference and mean difference. Between-group differences were assessed using Q_b statistics, and heterogeneity was evaluated using the I² statistics. Sensitivity and publication bias analyses were also performed.

RESULTS: Data from 30 articles representing 3262 athletes (12% female) were included. Sport-related concussion impacts produced significantly greater head acceleration magnitudes than non-concussive impacts, with large differences for both LHA (69.6 g vs 25.3 g; standardized mean difference = 2.42; 95% confidence interval 1.73-3.12) and RHA (4931 rad/s² vs. 1966 rad/s²; standardized mean difference = 1.99; 95% confidence interval 1.17-2.81). For SRC impacts, subgroup analyses revealed significant differences across sports (p < 0.001), age groups (LHA only, p = 0.01), sexes (LHA only, p < 0.001), and instrumentation types (LHA p < 0.001; RHA p = 0.02). The highest LHA values were observed in American Football (83.2 g), while the highest RHA values were recorded in rugby (7627 rad/s²). Higher LHA values were recorded for male athletes (78.2 g) compared with female athletes (44.2 g), and for high school athletes (88.3 g) compared with youth (61.4 g) and adult athletes (72.2 g). Helmet-mounted sensors recorded the highest LHA (79.0 g), and skin patches recorded the highest RHA (6938 rad/s²). No significant differences were found between games and practices.

CONCLUSIONS: In team sports, SRC impacts are associated with significantly higher LHA and RHA than non-concussive impacts. The observed overlap and contextual variability in head acceleration magnitudes highlight the importance of considering individual-specific and context-specific interpretation in SRC risk assessment and provide a foundation for improving head impact monitoring, injury prevention strategies, and athlete safety.

CLINICAL TRIAL REGISTRATION: PROSPERO CRD42024584070.

PMID:42189496 | DOI:10.1007/s40279-026-02448-x

Drugs Aging. 2026 May 26. doi: 10.1007/s40266-026-01303-y. Online ahead of print.

ABSTRACT

BACKGROUND: Orthostatic hypotension is recognized as a potential contributor to cognitive impairment in older adults. It is still unknown whether pharmacological treatment of orthostatic hypotension can affect cognition.

OBJECTIVE: The aim of this scoping review was to identify whether treatment of orthostatic hypotension with midodrine, droxidopa, and fludrocortisone had any effect on cognitive performance.

METHODS: We searched the databases of Embase and MEDLINE. Key eligibility criteria included observational studies or clinical trials using midodrine, droxidopa, or fludrocortisone to treat adult patients with orthostatic hypotension with cognition assessed. Key search terms used were “orthostatic hypotension,” “cognition,” “midodrine,” “fludrocortisone,” and “droxidopa.” Quality assessment was performed using the LEGEND (Let Evidence Guide Every New Decision) Evidence Evaluation System. A descriptive synthesis was undertaken because of heterogeneous study designs and assessments, categorizing studies by patient population, with no statistical pooling.

RESULTS: Five studies met the criteria for the scoping review. These studies investigated midodrine, droxidopa, and fludrocortisone used individually, or in combination, to treat orthostatic hypotension. Three studies found cognitive improvements with orthostatic hypotension treatment, one found negative cognitive side effects with orthostatic hypotension medications and one study found no significant change. Three patient populations were examined in these studies: patients with dementia, patients with parkinsonism, and patients with spinal cord injury. Included studies were small, observational, and interventional and cognitive outcomes ranged from symptom-based assessments to formal neuropsychological testing.

CONCLUSIONS: Limited conclusions can be drawn from these five studies because of non-standardized cognitive assessments, small sample sizes, and methodological variability. However, overall, this scoping review provides evidence that treatment of orthostatic hypotension might have a cognitive benefit in certain populations. Further observational studies and clinical trials are warranted to better elucidate whether combinations of midodrine, droxidopa, and fludrocortisone will work in specific patient populations to improve clinical outcomes.

PMID:42189477 | DOI:10.1007/s40266-026-01303-y

Environ Sci Pollut Res Int. 2026 May 26. doi: 10.1007/s11356-026-37859-w. Online ahead of print.

ABSTRACT

Rivers in industrial regions face significant pressure from anthropogenic activities, often resulting in degraded water quality. This study investigates long-term water quality dynamics of the Damodar River in West Bengal, India, using a multi-index approach and advanced statistics. Six established Water Quality Indices (WQIs) were computed using monthly data from 2014 to 2024 across ten monitoring sites. To reconcile the inconsistencies among individual indices, Principal Component Analysis (PCA) was applied to generate a unified metric termed the Principal Component Averaged WQI (PCAWQI). Furthermore, to quantify the causal impact of the COVID-19 lockdown (March-May 2020) on river health, we employed a Regression Discontinuity Design (RDD) using Bayesian structural time-series modeling (CausalImpact). The composite PCAWQI successfully captured spatial and temporal pollution gradients, highlighting critical midstream deterioration. Additionally, site-specific improvements in water quality were observed during the lockdown, with some sites exhibiting significant gains likely due to industrial inactivity. However, heterogeneous responses underscored the influence of socio-cultural and hydrological factors. Thus, by integrating dimensionality reduction and causal inference techniques, we developed a robust and replicable framework for water quality assessment. This framework can be utilized for environmental monitoring and policy evaluation in heavily industrialized river basins.

PMID:42189471 | DOI:10.1007/s11356-026-37859-w

Environ Sci Pollut Res Int. 2026 May 26. doi: 10.1007/s11356-026-37867-w. Online ahead of print.

ABSTRACT

Globally, the primary concern affecting the suitability of groundwater for drinking is the presence of numerous chemical contaminants in large-scale aquifer systems. Therefore, it is essential to establish reliable methods for assessing groundwater quality and determining the origin of groundwater contaminants. This study developed a comprehensive, data-driven method for evaluating the quality of large-scale groundwater in the State of Bihar, India, using a traditional Water Quality Index (WQI) and a statistically based Root Mean Square Water Quality Index (RMS-WQI). In the present study, four state-of-the-art machine learning algorithms, namely, Classification and Regression Tree (CART), Light Gradient Boosting Model (LGBM), Random Forest (RF), and Extreme Gradient Boosting Model (XGBoost), were evaluated to assess their utility in predicting groundwater quality. Of the four models tested, XGBoost demonstrated the highest degree of predictive performance, exhibiting high levels of accuracy in terms of R² values of 0.984 for the WQI and 0.994 for the RMS-WQI and low error metrics. Spatial diagnostics of the RMS-WQI model employing the Nash-Sutcliffe Efficiency (NSE), Model Efficiency Factor (MEF), and Percent Relative Error Index (PREI) identified heterogeneity in model performance, particularly in the data-volatile Gaya District, where NSE = -0.1. The uncertainty and robustness of the ML model were thoroughly evaluated using Monte Carlo simulations, which showed a reliability of 88.5%. Geochemical analysis indicated that both natural geochemical and anthropogenically influenced processes contributed to the variability in groundwater chemistry. Four main contributors to groundwater chemistry were identified through absolute principal component scores-multiple linear regression (APCS-MLR): mineral dissolution (32.7%), water-rock interactions (20.1%), mixed sources (16.3%), and anthropogenic inputs (13.2%). This innovative integrated methodology provides a scalable and cost- effective decision-making tool for predicting the spatial distribution of groundwater quality and supports the development of sustainable hydro-environmental management practices, while also supporting the achievement of United Nations Sustainable Development Goal 6.

PMID:42189468 | DOI:10.1007/s11356-026-37867-w

AIDS Behav. 2026 May 26. doi: 10.1007/s10461-026-05178-3. Online ahead of print.

ABSTRACT

African American/Black and Latine (AABL) emerging adults living with HIV have insufficient engagement along the HIV care continuum, and lower rates than their White peers. Some subpopulations (e.g., those with unsuppressed HIV viral load, immigrants) and aspects of their experiences are understudied. This study uses a sequential explanatory mixed-methods design to explore motivational appraisals (e.g., core health goals), generative capabilities (e.g., self-efficacy, resilience), and their relationships to HIV management in a diverse cohort. Structured baseline assessments were conducted (N = 271). A subset of these was purposively sampled for maximum variability for qualitative interviews (N = 41). Quantitative data were analyzed with descriptive statistics and a structural equation model (SEM). Primary outcomes were HIV care engagement and viral suppression. Quantitative results informed qualitative research questions; qualitative data were analyzed with directed content analysis. We used the joint display method to integrate results. Participants were 25 years old (SD = 2), on average. The majority (59%) were Latine/Hispanic, 41% were African American/Black. Nearly all were assigned male sex at birth (96%) and sexual minorities (93%). Approximately half (49.1%) were immigrants. Almost a third (28%) were not well-engaged in care and 19% were not virally suppressed. Motivation, adherence self-efficacy, and medication outcome expectancies were high regardless of viral suppression. In the SEM, self-efficacy had a positive direct effect on motivation (B = 0.24, p < 0.01); and resilience (B = 0.02, p = 0.04) and self-efficacy (B = 0.23, p < 0.01) each had positive direct effects on outcome expectancies. Motivation (B = 0.26, p = 0.02) had a positive direct effect on care engagement. There were no statistically significant direct effects on viral suppression. In the qualitative results, participants focused on medication/viral suppression, but not HIV care. We organized qualitative results into four themes: (1) why participants took medication (e.g., desire for longevity, to be “normal” and attractive, and avoid transmitting HIV); (2) how they took medication (e.g., learning over time, creating routines and habits); (3) factors that interfered (e.g., structural barriers/disruptions could overwhelm motivation); and (4) issues salient to immigrants (e.g., moving to the US for better care, honoring family by taking medication). This study advances knowledge on HIV management among diverse AABL emerging adults living with HIV, and identifies intervention targets.

PMID:42189459 | DOI:10.1007/s10461-026-05178-3

Prog Orthod. 2026 May 26;27(1):20. doi: 10.1186/s40510-026-00624-3.

ABSTRACT

AIMS: To quantify and compare the three-dimensional (3D) deviations of crown and root movements produced by two clear aligner systems based on different materials-SmartTrack (ST) and MasterControl S (MCS)-in first premolar extraction cases using a 3D crown-root registration approach.

METHODS: This retrospective cohort study included 29 patients (58 dental sides) treated with ST (n = 15) or MCS (n = 14). Pretreatment (T0) CBCT images were integrated with T0 and post-treatment (T1) intraoral scans and superimposed using palatal rugae as reference structures. Linear mixed-effects models (LMM) were applied to estimate between-material differences while adjusting for age, sex, and standardized planned movement magnitude. Estimates are reported with 95% confidence intervals (CI).

RESULTS: The two systems demonstrated no statistically significant difference in deviation in sagittal crown retraction of the maxillary central incisor (U1) (ST: 1.25 (1.30) mm; MCS: 2.13 (1.82) mm; LMM difference: – 0.81 mm; 95% CI – 1.89-0.28; P = 0.145). MCS demonstrated smaller deviation in sagittal root positioning for the second premolar (U5) (difference: 1.07 mm; 95% CI 0.21-1.93; P = 0.015) and first molar (U6) (difference: 1.04 mm; 95% CI 0.13-1.94; P = 0.025). ST showed improved control of U5 axial inclination (difference: 3.33°; 95% CI 0.27-6.39; P = 0.033) and torque (difference: 3.04°; 95% CI 0.08 to 6.00; P = 0.044). Both systems exhibited a consistent “roller-coaster effect”, with no significant difference in unplanned U1 extrusion (difference: 0.14 mm; 95% CI – 0.73-1.02; P = 0.747).

CONCLUSIONS: The biomechanical performance of clear aligner systems appears to vary depending on tooth position and movement vector. SmartTrack demonstrated better control of premolar angulation and torque, whereas MasterControl S showed closer agreement with the planned sagittal root position.

PMID:42189428 | DOI:10.1186/s40510-026-00624-3

MedScience. 2026 May 26. doi: 10.1007/s11684-026-1205-3. Online ahead of print.

ABSTRACT

X-chromosomal genetic variants have been understudied in end-stage renal disease (ESRD), which holds the promise to provide valuable insights into sexually dimorphic traits and diseases. Here we performed an X chromosome-wide association study (XWAS) in a Chinese cohort (N = 2750), comprising 1489 cases with ESRD and 1261 controls, to identify locus associated with ESRD risk. One locus showing a consistent effect direction across sex but primarily supported by the male cohort was identified in COL4A5 (P = 2.43 × 10^-6) in the metaanalysis combining summary statistics from the sex-stratified XWAS. COL4A5 codes for the alpha chain of type IV collagen, which is essential for the integrity of the glomerular basement membrane and normal glomerular function. Two male-specific loci, MIR3202-2 (P = 6.85 × 10^-5) and SYTL4 (P = 1.71 × 10^-5), were identified in the sex-stratified XWAS in males, and expression of SYTL4, TSPAN6, NOX1, CSTF2, and PCDH19 was found to be influenced by the ESRD loci near SYTL4 based on expression quantitative trait loci (eQTL) results from the Genotype-Tissue Expression (GTEx) project. In summary, our findings revealed three X-chromosome loci linked to ESRD risk, which provided foundational knowledge for genetic risk prediction and advanced our understanding of the molecular underpinnings of ESRD.

PMID:42189395 | DOI:10.1007/s11684-026-1205-3

MedScience. 2026 May 26. doi: 10.1007/s11684-026-1250-y. Online ahead of print.

NO ABSTRACT

PMID:42189394 | DOI:10.1007/s11684-026-1250-y

Forensic Sci Med Pathol. 2026 May 26. doi: 10.1007/s12024-026-01270-1. Online ahead of print.

ABSTRACT

This study aimed to assess the reliability of the Demirjian and Olze staging systems for mandibular third molars using panoramic radiographs in a medico-legal context. A retrospective pilot study was conducted on 25 medico-legal cases from a Medico-Legal Institute. Panoramic radiographs were evaluated using the Demirjian (A-H) and Olze (0-3) methods. Chronological age was compared with radiographic findings. Statistical analyses included sensitivity, specificity, predictive values, and Cohen’s kappa coefficient. Demirjian stage H and Olze stages 2-3 were observed only in individuals aged 18 years or older, whereas stages C-G and Olze stage 0 were found exclusively in those under 18. Both staging methods demonstrated high diagnostic performance within this sample, with sensitivity, specificity, and predictive values reaching 100% for identifying legal adulthood. Agreement between methods was complete (κ = 1.00), with high inter- and intra-observer reliability (κ = 0.84; ICC = 0.92). No significant sex-related differences were observed. Panoramic analysis of third molars appears to be a promising, reproducible, and ethically acceptable approach for distinguishing minors from adults in this medico-legal context. However, given the pilot design and limited sample size, these findings should be interpreted with caution. Larger multicenter studies, including the integration of skeletal indicators, are required to establish robust and generalizable reference standards.

PMID:42189383 | DOI:10.1007/s12024-026-01270-1