Tag: pubmed

Genes Genomics. 2025 Sep 16. doi: 10.1007/s13258-025-01673-4. Online ahead of print.

ABSTRACT

BACKGROUND: Identifying microbiome markers associated with ordered phenotypes, such as disease stages or severity levels, is crucial for understanding disease progression and advancing precision medicine. Despite this importance, most existing methods for differential abundance analysis are designed for binary group comparisons and do not incorporate ordinal information, limiting their ability to capture trends across ordered categories.

OBJECTIVE: To develop and evaluate statistical methods that explicitly account for ordinal phenotype structure in microbiome data, addressing challenges such as sparsity and zero inflation, and improving the detection of meaningful microbial associations.

METHODS: In this study, we propose and evaluate three novel approaches specifically tailored for microbiome association analysis with ordered groups: the binary optimal test, the linear trend test, and the proportional odds model-based permutation test (POMp). These methods explicitly account for the ordinal structure of phenotypes and address the sparsity and zero-inflation commonly observed in microbiome data through permutation-based inference. We applied the proposed methods to three publicly available gut microbiome datasets, including two related to obesity and one concerning colorectal cancer.

RESULTS: All three proposed methods successfully identified differentially abundant features (DAFs) that exhibited stronger ordinal associations compared to those identified by existing methods. In particular, POMp consistently outperformed other approaches in terms of correlation with phenotype order, demonstrating its potential to identify biologically relevant markers.

CONCLUSION: The findings of this study highlight the importance of incorporating ordinal information in microbiome studies and provide robust statistical tools for advancing microbial biomarker discovery in complex disease contexts.

PMID:40956524 | DOI:10.1007/s13258-025-01673-4

Clin Drug Investig. 2025 Sep 16. doi: 10.1007/s40261-025-01482-3. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Dyslipidaemia is a key modifiable risk factor for atherosclerotic cardiovascular disease. However, achieving recommended low-density lipoprotein cholesterol (LDL-C) target levels is challenging owing to dose-dependent adverse effects and limited tolerability of high-dose statins. This study evaluated the real-world efficacy and safety of combining very-low-dose rosuvastatin (2.5 mg) with ezetimibe (10 mg) in adult patients with dyslipidaemia across different cardiovascular risk strata.

METHODS: This multicentre prospective study in South Korea enrolled 2,388 patients. Participants were stratified into low-, moderate-, or high-risk groups on the basis of the 2019 European Society of Cardiology and European Atherosclerosis Society guidelines. Lipid profiles and safety outcomes were assessed at baseline and after 12 weeks. The primary and secondary outcomes were LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) target level achievements, respectively, and adverse events were monitored.

RESULTS: After 12 weeks, LDL-C target levels were achieved by 82.6% of low-risk (< 116 mg/dL), 73.9% of moderate-risk (< 100 mg/dL), and 50.4% of high-risk (< 70 mg/dL) patients. Non-HDL-C target level achievement followed a similar trend. Combination therapy with ezetimibe and low-dose statin resulted in significant LDL-C reductions, compared with statins alone. Adverse events were infrequent (0.6%), and only 0.2% of patients discontinued treatment owing to medication-related concerns.

CONCLUSIONS: Very-low-dose rosuvastatin-ezetimibe combination therapy significantly lowered LDL-C levels and improved lipid profiles across various risk groups, demonstrating a favourable safety profile. These findings support its use as an effective, well-tolerated option for managing dyslipidaemia. Longer-term studies are warranted to evaluate sustained lipid control and cardiovascular outcomes.

PMID:40956520 | DOI:10.1007/s40261-025-01482-3

Hormones (Athens). 2025 Sep 16. doi: 10.1007/s42000-025-00718-3. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic inflammation plays a pivotal role in autoimmune thyroiditis (AT), yet traditional biomarkers fail to predict systemic complications. The systemic immune-inflammation Index (SII) and the systemic inflammation response index (SIRI), which integrate multiple immune cell counts, may serve as novel prognostic tools for assessing AT-related mortality.

METHODS: This study analyzed data from 1053 AT patients in the 2007-2012 NHANES cycles. SII and SIRI were calculated using standardized complete blood count parameters. All-cause mortality was assessed through linkage with the National Death Index. Cox proportional hazard models with sequential adjustments evaluated the associations between inflammatory indices and mortality. Nonlinear relationships and critical thresholds were examined using restricted cubic splines.

RESULTS: Elevated SII and SIRI were significantly associated with increased mortality risk. After full adjustment, each log-unit increase in SII (HR = 1.819, 95% CI:1.347-2.457) and each unit increase in SIRI (HR = 1.314, 95% CI:1.124-1.537) independently predicted higher mortality. Threshold analysis identified critical inflection points at ln-SII ≥ 6.18 (HR = 2.629, 95% CI:1.431-4.831) and SIRI ≥ 1.01 (HR = 1.257, 95% CI:1.030-1.535), beyond which mortality risk escalated sharply. Kaplan-Meier curves confirmed significant survival disparities across tertiles (log-rank p < 0.001). Stratified analyses showed consistent associations across demographic and clinical subgroups.

CONCLUSION: SII and SIRI are robust, cost-effective biomarkers for predicting mortality in AT, with defined thresholds marking transitions from compensatory to pathological inflammation. These indices provide a comprehensive reflection of systemic immune dysregulation, offering actionable insights for risk stratification and targeted interventions. Future studies should validate these findings in diverse populations and explore anti-inflammatory therapies to improve outcomes in AT patients.

PMID:40956512 | DOI:10.1007/s42000-025-00718-3

Odontology. 2025 Sep 16. doi: 10.1007/s10266-025-01200-7. Online ahead of print.

ABSTRACT

This in vitro study aimed to evaluate the changes in surface integrity of dental enamel after bleaching using gels with different compositions followed by an erosive challenge. Bovine enamel specimens (4 × 4 × 2 mm; n = 12/group) stored in artificial saliva were treated with bleaching gels containing carbamide peroxide (CP) or hydrogen peroxide (HP) with or without calcium polyphosphate (CaPP) followed by an erosive challenge. In Experiment 1, 10% commercial CP (CPC), CPC + 2% NaF, 10% manipulated CP (CPM), CPM + 2% NaF, 10% CP + 0.5 wt% CaPP, 10% CP + 1.5 wt% CaPP, manipulated gel without CP, or no bleaching were applied for 14 days. In Experiment 2, CP was switched with 35% HP, and all gels were applied for two sessions. Thereafter, all samples were subjected to a 5-day erosive challenge using 1% citric acid (pH 3.5) for 120 s. Enamel surface loss was assessed using contact profilometry and scanning electron microscopy (SEM). Statistical analysis was performed using a generalized linear model (α = 0.05). Compared with that in the CP + 0.5% CaPP and HP + 0.5% CaPP groups, enamel loss was significantly greater in the CPM and CPC groups and HPM and HPC groups in Experiments 1 and 2, respectively. SEM analysis revealed less surface degradation in the groups containing 0.5% CaPP, with greater preservation of the prismatic and interprismatic enamel structure. Both low- and high-concentration bleaching gels containing 0.5% CaPP improved enamel preservation after an erosive challenge compared to that with gels without CaPP. Thus, the addition of CaPP may help minimize enamel damage during bleaching by reducing mineral loss.

PMID:40956501 | DOI:10.1007/s10266-025-01200-7

Ir J Med Sci. 2025 Sep 16. doi: 10.1007/s11845-025-04076-2. Online ahead of print.

ABSTRACT

BACKGROUND: Growing patient interest in the direct anterior approach (DAA) has led to increased Internet promotion by surgeons.

AIMS: The aim of this study was to investigate Internet promotion of the DAA by surgeons in Australia, New Zealand, Ireland and the UK. Further, we aimed to determine if surgeons offering the DAA discussed the potential benefits of the approach more frequently than other surgeons.

METHODS: Orthopaedic surgeons were identified from the websites of the Australian Orthopaedic Association, New Zealand Orthopaedic Association, UK National Joint Registry, and Irish Institute of Trauma and Orthopaedic Surgery. Each surgeon website was investigated for claims made regarding the risks and benefits of the DAA, as well as the literature used to support these claims.

RESULTS: In total, 6.4% (n = 177) of websites identified mentioned the DAA: 128 (72.3%) websites were associated with surgeons offering the DAA, while 49 (27.7%) websites were associated with surgeons not offering the DAA. Potential benefits were mentioned in 74% of websites, while 36.7% made reference to risks; 9% cited peer-reviewed literature. When comparing websites of surgeons who offer the DAA with the websites of surgeons who do not, there was a statistically significantly increased rate of mentioning any benefit (p = 0.016), less tissue damage (p = 0.041), less blood loss (p = 0.004), faster recovery (p = 0.004), and fewer dislocations (p = 0.002).

CONCLUSION: A small number of surgeons in these countries promote the DAA online. Surgeons offering the DAA are more likely to report the potential benefits of the procedure than surgeons not offering the DAA.

PMID:40956496 | DOI:10.1007/s11845-025-04076-2

Eur J Pediatr. 2025 Sep 16;184(10):619. doi: 10.1007/s00431-025-06470-5.

ABSTRACT

OBJECTIVES: This study aimed to assess the impact of malnutrition on liver and spleen stiffness in children using shear wave elastography (SWE) and to compare the findings with those of healthy controls.

METHODS: A total of 308 children aged 0-18 years were prospectively enrolled and classified as either malnourished or healthy according to World Health Organization (WHO) growth reference standards (weight-for-height Z-scores for children under 5 years and BMI-for-age Z-scores for those aged 5 years and older). Liver and spleen stiffness measurements were obtained using SWE by a single pediatric radiologist blinded to nutritional status. Statistical comparisons were performed between groups, across malnutrition severity subgroups, and within different age categories.

RESULTS: Liver stiffness did not differ significantly between malnourished children overall and healthy controls, but it was markedly higher in those with severe malnutrition compared to mild or moderate cases (p = 0.018). Spleen stiffness was significantly lower in malnourished children aged 0-6 years compared to controls (p < 0.001). Both liver and spleen stiffness values increased with age (p = 0.014 and p = 0.013, respectively).

CONCLUSION: Our findings indicate that malnutrition is associated with age- and severity-dependent alterations in liver and spleen stiffness. Liver stiffness was elevated only in children with severe malnutrition, whereas spleen stiffness was reduced in younger children but not in older ones. SWE may serve as a valuable non-invasive tool for assessing organ-level effects of malnutrition, and these results may guide future research on the reversibility and clinical significance of such changes.

WHAT IS KNOWN: • Childhood malnutrition is associated with profound metabolic and structural alterations in vital organs such as the liver and spleen. However, its impact on organ biomechanics, as assessed by elastography, has not been clearly defined.

WHAT IS NEW: • Malnutrition leads to organ-specific biomechanical changes, with increased liver stiffness in severe cases and reduced spleen stiffness particularly in younger children. • Shear wave elastography provides a non-invasive approach to characterize these alterations.

PMID:40956488 | DOI:10.1007/s00431-025-06470-5

Pulm Ther. 2025 Sep 16. doi: 10.1007/s41030-025-00313-2. Online ahead of print.

ABSTRACT

INTRODUCTION: It is important that treatment recommendations reflect real-world data when available, as randomised controlled trials have stringent eligibility criteria and do not represent the entire asthma population or their usual ecosystem of care. Limited real-world evidence has compared the effectiveness of fluticasone furoate/vilanterol (FF/VI) and budesonide/formoterol (BUD/FOR) to date in asthma; we explored this in England using patients from general practice.

METHODOLOGY: We retrospectively compared new FF/VI users and new BUD/FOR users from 1 December 2015 to 28 February 2019, based on de-identified data from the Clinical Practice Research Datalink. The baseline period pre-index was ≥ 1 year; the follow-up period was 1 year. At index, eligible adults (≥ 18 years) with diagnosed asthma had ≥ 1 prescription for FF/VI or BUD/FOR, ≥ 1 years’ general practitioner registration and records eligible for linkage to Hospital Episode Statistics. Chronic obstructive pulmonary disease was an exclusion criterion. The primary study outcome assessed the overall asthma exacerbation rate in new FF/VI or BUD/FOR users. Secondary outcomes included oral corticosteroid (OCS) use and medication persistence (analysed using Kaplan-Meier curves). For each treatment comparison, propensity scores were generated and confounding between baseline group characteristics was adjusted via inverse probability of treatment weighting, separately carried out for each study outcome. Intercurrent events (ICEs) were considered for analyses, such as death, loss to follow-up, rescue-medication use, treatment discontinuation or switching.

RESULTS: Between groups, baseline attributes were well balanced. Annual per-person rates of exacerbation were numerically similar in the while on-treatment population (measuring outcome until ICE; FF/VI, 0.1356; BUD/FOR, 0.1583 [P = 0.3023]). Patients who continued initiation treatment for 1 year without interruption had significantly lower annual per-person exacerbation rates with FF/VI (0.0722 [n = 425]) versus BUD/FOR (0.2258 [n = 546]) (rate ratio 0.3197 [P = 0.0003]). Patients indexed on FF/VI had significantly fewer OCS prescriptions and lower OCS dosage versus BUD/FOR (respective coefficients: – 0.29 [P = 0.0352]; 0.41 [P = 0.0004]) and improved treatment persistence (hazard ratio: 0.62 [P < 0.0001]).

CONCLUSIONS: Patients who continued initiation treatment for a year without interruption had reduced exacerbation rates with FF/VI versus BUD/FOR. The FF/VI group also had reduced treatment discontinuation and OCS use.

PMID:40956480 | DOI:10.1007/s41030-025-00313-2

Clin Oral Investig. 2025 Sep 16;29(10):458. doi: 10.1007/s00784-025-06556-2.

ABSTRACT

OBJECTIVES: Total temporomandibular joint (TMJ) replacement is indicated when conservative treatments fail in conditions that significantly alter joint anatomy. This study evaluated the impact of early and prolonged physiotherapy on functional outcomes after TMJ prosthetic replacement.

MATERIALS AND METHODS: Thirty-six patients (94.4% female; mean age, 49.8 years) underwent TMJ prosthetic replacement between July 2020 and December 2023, with a mean follow-up of 23.5 months. Functional outcomes included TMJ range of motion (ROM), pain according to a visual analog scale (VAS), and masticatory function (diet and chewing score on the TMJ-S-QoL scale). Patients were divided into two groups based on physiotherapy: early and prolonged (initiated within the first month and continued for ≥ 6 months) vs. absent/delayed/non-prolonged.

RESULTS: Overall, patients showed significant (p < 0.001) improvements in ROM (+ 9.8 mm), pain score (-5.2 points), and diet and chewing score (+ 1.7 points). At 1 year, early and prolonged physiotherapy was associated with significantly better masticatory outcomes. Recovery kinetics showed faster and greater improvements between 1 and 6 months in this group. ROM and pain improvements also favored early rehabilitation, although the differences were not statistically significant.

CONCLUSION: Early and sustained physiotherapy initiated within the first postoperative month significantly enhances masticatory recovery following TMJ prosthetic replacement. These findings support the integration of structured rehabilitation protocols to optimize long-term functional outcomes.

PMID:40956466 | DOI:10.1007/s00784-025-06556-2

J Comp Eff Res. 2025 Sep 16:e240168. doi: 10.57264/cer-2024-0168. Online ahead of print.

ABSTRACT

Randomized controlled trials (RCTs) are regarded as the highest level of evidence in medical research, but RCTs also have their drawbacks. Over the years, several alternative study designs have been introduced to address these problems. However, many of the alternative designs are often regarded as inferior to RCTs or currently not suitable for widespread implementation due to, for example, ethical or statistical problems. Thus, there is a need for study designs that have the same level of validity as RCTs, but are also suitable for large-scale implementation. The cohort intervention random sampling study (CIRSS) with historical controls meets these requirements, by combining the strengths of abovementioned designs. The CIRSS with historical controls has the potential to optimize implementation of promising new treatments as fluidly and rapidly as possible, representing real-world clinical population. Further research is required to address the range of analyses, implementation, issues, barriers and facilitators and ethical questions related to CIRSS.

PMID:40955624 | DOI:10.57264/cer-2024-0168

J Periodontol. 2025 Sep 16. doi: 10.1002/jper.70011. Online ahead of print.

ABSTRACT

BACKGROUND: Accurate periodontal disease diagnosis is essential for optimal treatment planning and patient care. However, variability in applying the 2017 Periodontal Classification may affect diagnostic reliability and treatment outcomes. This study investigated diagnostic accuracy and consistency among periodontists, periodontal residents, and dental interns in Saudi Arabia.

METHODS: Forty-four participants, including 13 periodontists, 14 periodontal residents, and 17 dental interns, independently classified 25 periodontitis cases. Agreement with a gold-standard diagnosis, established by expert periodontists using the 2017 Classification System, was assessed using descriptive statistics. Chi-square tests with Bonferroni-adjusted z-tests were used to compare agreement levels between rater groups. Inter-rater reliability was calculated using Fleiss’ kappa, while Cohen’s kappa was used to assess intra-rater reliability.

RESULTS: Periodontists demonstrated the highest agreement with the gold standard (92.0%) for periodontitis diagnosis. Staging agreement was highest among residents (51.7%) and periodontists (49.1%). Grading accuracy was highest for grade C cases across all groups (60.7%). Underestimation was common across rater groups, with interns exhibiting the highest rates in staging (49.6%) and grading (58.3%). The second assessment demonstrated improved diagnostic accuracy across all groups. Inter-rater reliability ranged from fair to moderate across rater groups (κ = 0.22-0.60). Intra-rater reliability was highest among interns, indicating substantial agreement (κ = 0.63-0.75).

CONCLUSION: Findings highlight considerable variability in the application of the 2017 Periodontal Classification among dental professionals, underscoring the role of clinical experience and training in influencing diagnostic accuracy. Structured calibration and targeted educational strategies are essential to improve diagnostic consistency, minimize misclassification, and support optimal patient care.

PLAIN LANGUAGE SUMMARY: Understanding gum disease correctly is important for providing patients with the right treatments. This study looked at how accurately different groups of dental professionals – specialists in gum disease (periodontists), dentists in training (residents), and recent dental graduates (interns) – could diagnose cases of periodontitis using a new system called the 2017 Periodontal Classification. A group of expert periodontists created a “gold-standard” diagnosis for comparison. We found that periodontists were the most accurate, while interns had more difficulty correctly identifying disease severity. Across all groups, many participants underestimated how serious the cases were. Participants were better at recognizing advanced disease compared to milder forms. When the participants repeated the diagnosis of the cases later, their accuracy improved, suggesting that practice and training help. Our results show that diagnosing gum disease can vary depending on experience and training. The study highlights the need for ongoing education and practice to make sure that all dental professionals can diagnose gum disease reliably, which is important for making treatment decisions and improving patient care.

PMID:40955590 | DOI:10.1002/jper.70011