Category: Statistics

J Periodontol. 2025 Dec 10. doi: 10.1002/jper.70024. Online ahead of print.

ABSTRACT

BACKGROUND: This first-in-human clinical study aimed to evaluate the safety and efficacy of a bioglass incorporated in a toothpaste, in reducing dentin hypersensitivity (DH) compared to a sodium fluoride (NaF) toothpaste over a 2-week period.

METHODS: A double-blind, randomized, parallel-arm, proof-of-concept clinical trial was conducted with 46 participants experiencing self-reported and clinically confirmed DH. Participants were assigned to 1 of 2 groups: (1) Test toothpaste (5 wt% bioglass with 1425 ppm fluoride as NaF), or (2) NaF toothpaste (1425 ppm fluoride). Outcomes included Schiff Airblast Sensitivity Score (primary endpoint), Visual Analog Scale (VAS) for pain, and Yeaple Probe tactile sensitivity (secondary endpoints). Statistical analyses, including analysis of covariance (ANCOVA) and descriptive statistics, were performed to evaluate intergroup differences.

RESULTS: The Test group exhibited a statistically significant reduction in Schiff Airblast Sensitivity Scores at Day 14 compared to the NaF group (ΔMean: -0.8 vs. -0.5, p = 0.0341). Significant improvements were also observed in VAS pain scores in as little as 2 days (ΔMean: -1.03 vs. 0.04, p = 0.0057). Rapid pain relief was noted within 2 days, indicating both immediate and cumulative effects. The difference in tactile scores was not statistically significant between groups although greater change was seen with Test toothpaste (ΔMean 13 vs. 3 g; p = 0.068). No severe adverse events were reported, and safety profiles were comparable across groups.

CONCLUSION: The toothpaste containing the bioglass demonstrated superior efficacy in alleviating DH symptoms at both early and later time points through its mechanism of rapid tubule occlusion. This innovative approach aligns with World Health Organization (WHO) recommendations for fluoride use and addresses unmet needs in DH management globally. Further research is warranted to explore its long-term applications in preventive and restorative dentistry.

CLINICAL TRIALS REGISTRATION: U.S. National Institutes of Health Clinical Trials Registry (http://www.

CLINICALTRIALS: gov) ID NCT06166745.

PMID:41373067 | DOI:10.1002/jper.70024

J Dent Child (Chic). 2025 Sep 15;92(3):129-136.

ABSTRACT

Purpose: To assess the fracture resistance of prefabricated esthetic crowns for primary molars. Methods: Seventy-two human mandibular second primary molars were divided into three groups: preveneered stainless steel crowns (VSS), prefabricated zirconia crowns (PZ) and BioFlx crowns (BF). Crowns were cemented with glass ionomer cement; for each group, 12 samples were tested for fracture resistance and 12 samples underwent 5,000 thermocycles before testing. The fracture mode was assessed for all the samples. Differences in the fracture resistance values between the groups were tested using analysis of variance (ANOVA), followed by Tukey’s post hoc test, while the distribution of fracture modes was tested using Fisher’s exact test. Statistical significance was set at P =0.05 and analyses were conducted using SPSS version 25.0 software. Results: ANOVA tests indicated a significant difference in fracture resistance among the test groups (P <0.001). The groups were ranked as follows: before thermocycling- (1) PZ group (3,327±1497), (2) BF group (1,694±163) and (3) VSS group (536±12); and after thermocycling-(1) PZ group (3,308±162), (2) BF group (1,579±77) and (3) VSS group (413±16). Tukey’s post hoc analysis indicated that the PZ group exhibited a significantly higher fracture resistance than the BF and VSS groups (P <0.001). The VSS group showed a predominance of minimal cracks (5.6 percent) and loss of less than half of the crown (11.1 percent). Conclusions: PZ yielded the highest resistance, followed by BF crowns. VSS may require caution in high-stress areas due to their susceptibility to esthetic component failure, although the underlying crown remains functional.

PMID:41373045

Stem Cell Res Ther. 2025 Dec 10. doi: 10.1186/s13287-025-04854-w. Online ahead of print.

ABSTRACT

BACKGROUND: There is controversy about the benefits of bone marrow mononuclear cells (BMMC) to improve left ventricular dysfunction (LVD) in patients with coronary artery disease. We sought to evaluate the safety, feasibility and efficacy of the intracoronary infusion of BMMC to improve left ventricular ejection fraction (LVEF) in patients with chronic total coronary artery occlusions (CTO).

METHODS: Prospective, randomized, open-label and controlled study. Patients with a percutaneous revascularization of CTO (CTO-PCI) three months before and persistent LVD (LVEF < 45%) were included and randomized in a 1:1 ratio to receive intracoronary infusion of autologous BMMC plus conventional medical treatment or conventional treatment alone (control group). The primary efficacy endpoint was the absolute change in LVEF by cardiac magnetic resonance imaging (CMR) at 6-month follow-up. The functional capacity status by NYHA class, the overall mortality and the adverse cardiac events rate were also evaluated in the 24-month follow-up period.

RESULTS: Twenty-eight patients were included, 13 received intracoronary infusion of BMMC and 15 received standard care. No major procedural complications occurred during BMMC infusion, and the rates of overall mortality and adverse cardiac events in follow-up were similar. At 6-month follow-up, the absolute change in LVEF was greater in BMMC group, without reaching statistical significance [∆ LVEF 0% ( – 5 to 0) in the control group vs. 2.5% ( – 2.7 to 4) in the BMMC group, median between-groups difference 2.5% ( – 2 to 4.5), p = 0.118)]. The change in NYHA class did not differ between treatment arms at any stage of follow-up.

CONCLUSIONS: The intracoronary infusion of BMMC in patients with previous CTO-PCI and persistent LVD seemed to be safe and feasible. There was a numerical but not statistically significant difference in terms of LVEF recovery favouring the BMMC group. The study offers a novel design for future larger trials to clarify the impact of BMMC therapy in patients with CTO. Trial registration The trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT number: 2013-000915-26).

PMID:41373040 | DOI:10.1186/s13287-025-04854-w

J Intensive Care. 2025 Dec 11. doi: 10.1186/s40560-025-00840-9. Online ahead of print.

ABSTRACT

BACKGROUND: The pharmacokinetics of prolonged remimazolam infusion in patients undergoing long-term mechanical ventilation remain unclear. This study aimed to evaluate the pharmacokinetics of remimazolam administered continuously for 24 h.

METHODS: This open-label pharmacokinetic analysis enrolled patients requiring mechanical ventilation into two groups: the surgical group, which received remimazolam during and after surgery, and the medical ICU group, which received remimazolam in the intensive care unit (ICU). Remimazolam was administered at a fixed rate of 0.1 mg/kg/h for ≥ 24 h, and blood samples were collected at regular intervals. Plasma remimazolam concentrations were measured by tandem mass spectrometry.

RESULTS: Twenty patients (10 in each group) completed the study. The median duration of remimazolam infusion was 24.0 h in the surgical group and 102.0 h in the medical ICU group. The steady-state plasma concentrations in both the surgical and medical ICU groups exhibited modest intrasubject variability (4.46-32.73%) and moderate intersubject variability (16.45-31.71%), with all values falling within clinically acceptable intermediate ranges. The plasma remimazolam concentration at the end of infusion was 130.7 ng/mL (95% confidence interval [CI] 115.2-146.1) in the surgical group and 134.3 ng/mL (95% CI 98.7-170.0) in the medical ICU group. Noncompartmental analysis showed that the clearance was 54.3 L/h (95% CI 47.6-61.8) and 55.6 L/h (95% CI 42.8-72.1) (P = 0.856), while the volume of distribution at steady state was 284 L (95% CI 215-376) and 316 L (95% CI 142-707) (P = 0.780), with no statistically significant differences between the groups.

CONCLUSIONS: In this preliminary study, both the surgical ICU group (approximately 24 h) and the medical ICU group (beyond 24 h) showed no evidence of time-dependent accumulation of plasma remimazolam, indicating a generally stable pharmacokinetic profile under the examined conditions.

TRIAL REGISTRATION: In compliance with the Japanese Clinical Trials Act, the study was classified as a Specified Clinical Trial owing to the use of unapproved pharmaceuticals, which were reviewed by a certified review board (CRB) and registered in the Japan Registry of Clinical Trials (jRCTs041200076) on December 15, 2020.

PMID:41373030 | DOI:10.1186/s40560-025-00840-9

Adv Rheumatol. 2025 Dec 10. doi: 10.1186/s42358-025-00458-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether the combination of exercise and intra-articular injection (IAI) effectively improves pain, function, and quality of life in patients with knee osteoarthritis (OA) compared to any control group in the short, medium, and long term through a systematic review.

METHODS: A comprehensive search strategy was applied in the databases Embase, PubMed, MEDLINE, CENTRAL, CINAHL, and PEDro. Inclusion criteria focused on randomized controlled trials examining the effects of exercise combined with IAI in patients with knee OA, with outcomes assessed at short-, medium-, and long-term follow-ups. The primary outcomes were pain and function. The quality of the evidence was evaluated using the GRADE system.

RESULTS: Eleven studies, comprising 802 participants, were included. All studies investigated the combination of IAI and exercise. A statistically significant difference in pain was observed: in the short and medium term, the Botulinum toxin IAI group demonstrated superior pain reduction compared to the Hyaluronic acid IAI group (MD -1.32, 95% CI -2.20 to -0.44 and MD -9.09, 95% CI -13.16 to -5.01, respectively). In the medium term, Saline IAI was more effective than Corticosteroid IAI (MD 1.99, 95% CI 0.49 to 1.90). Regarding function, Saline IAI outperformed IAI with any medication in the short term (MD 0.50, 95% CI 0.20 to 0.79). In terms of quality of life, the Corticosteroid IAI group demonstrated superior physical function and mental health outcomes compared to the Saline IAI group in the medium term (MD -0.43, 95% CI -0.77 to -0.08 and MD -0.38, 95% CI -0.76 to -0.01, respectively). In the long term, physical function improved more with IAI combined with exercise compared to exercise alone.

CONCLUSION: Given the very low quality of the evidence, it is not possible to definitively conclude that the combination of IAI and exercise is more effective than IAI or exercise alone in patients with knee OA. Further high-quality studies are needed to establish more definitive conclusions.

REGISTRATION: The International Prospective Register of Systematic Reviews (PROSPERO): CRD42021277729.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41373020 | DOI:10.1186/s42358-025-00458-3

J Ovarian Res. 2025 Dec 10. doi: 10.1186/s13048-025-01925-7. Online ahead of print.

NO ABSTRACT

PMID:41373018 | DOI:10.1186/s13048-025-01925-7

Syst Rev. 2025 Dec 10. doi: 10.1186/s13643-025-03011-x. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive subtype of steatotic liver disease, imposes a substantial global health burden due to its association with obesity and metabolic syndrome. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrate therapeutic potential through pleiotropic mechanisms, including appetite regulation, metabolic enhancement, and anti-inflammatory activity. However, clinical evidence remains limited by methodological heterogeneity and insufficient long-term efficacy data, necessitating a rigorous systematic evaluation.

METHODS: This protocol for a systematic review and meta-analysis will include randomized controlled trials (RCTs) evaluating GLP-1 RAs versus placebo in adults with biopsy-confirmed MASH. Comprehensive searches of PubMed, Web of Science, Embase, and the Cochrane Library will be conducted using predefined strategies. Two independent reviewers will perform study screening, data extraction, and risk-of-bias assessment with the Cochrane ROB 2 tool. Primary outcomes are histological: (1) MASH resolution without fibrosis worsening, and (2) fibrosis improvement without MASH deterioration. Secondary outcomes encompass physiological and biochemical parameters. Data synthesis will utilize random-effects meta-analysis, complemented by meta-regression to explore heterogeneity sources. Trial sequential analysis (TSA) will be used to control random errors (α = 0.05, power = 80%) and validate evidence sufficiency, strengthening result reliability. Sensitivity analyses will assess robustness. Statistical analyses will employ RevMan 5.4 and R 4.3.1. Evidence certainty will be evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework.

ETHICS AND DISSEMINATION: Ethical approval is not required as this study synthesizes published data. Findings will be disseminated through peer-reviewed publication and conference presentations.

SYSTEMIC REVIEW REGISTRATION: PROSPERO CRD420251090801.

PMID:41373001 | DOI:10.1186/s13643-025-03011-x

Trials. 2025 Dec 10. doi: 10.1186/s13063-025-09315-6. Online ahead of print.

ABSTRACT

BACKGROUND: In clinical trials, evaluating de-intensified oncologic treatment strategies can help reduce treatment-related toxicities while preserving patients’ quality of life. However, de-intensification is typically evaluated in cancers with a low relapse rate, and if the cancer type is uncommon, a randomized trial may require an impractically extended period to accumulate sufficient events for reliable inferential conclusions.

METHOD: This paper introduces a Bayesian adaptive method for the single-arm trial design that provides efficient analysis of survival data under these constraints. By incorporating data from previous studies to establish prior knowledge and a historical control arm, this approach enables robust and accurate estimations and predictions for trial design, sample size determination, and inferential decision-making. To support the implementation of this method, we developed an R package called “BayesAT,” which offers significant flexibility in modelling and supports multi-stage interim analyses, particularly for evaluating de-intensified oncologic treatments.

RESULT: Our approach is validated through comprehensive simulation studies and sensitivity analyses. Additionally, this algorithm has been applied to a pediatric Hodgkin lymphoma trial, showcasing its capability to effectively leverage information from previous studies and conduct interim analyses that expedite conclusions regarding treatment efficacy.

PMID:41372997 | DOI:10.1186/s13063-025-09315-6

Parasit Vectors. 2025 Dec 10. doi: 10.1186/s13071-025-07142-x. Online ahead of print.

ABSTRACT

BACKGROUND: Members of the genus Trichinella are muscle-dwelling zoonotic parasites of global importance for public health, animal husbandry, and trade. Trichinella chanchalensis (T13) is the newest species in the genus, first described in the Yukon and the Northwest Territories, for which the geographical distribution remains unknown due to limitations of the gold standard test for genotyping (multiplex polymerase chain reaction [PCR]). Our primary objective was to determine whether T. chanchalensis was present in Alaska, using a new molecular method that enables the description of the prevalence, co-infection, host associations, and risk factors for Trichinella spp. infection in wild carnivores.

METHODS: Trichinella spp. larvae were recovered through artificial digestion of muscle and genotyped using next-generation sequencing (NGS).

RESULTS: Trichinella spp. larvae were detected in 53/157 (34%) animals, namely wolverines (Gulo gulo), arctic foxes (Vulpes lagopus), red foxes (Vulpes vulpes), coyotes (Canis latrans), wolves (Canis lupus), brown bears (Ursus arctos), and polar bears (Ursus maritimus), but not in black bears (Ursus americanus) or lynx (Lynx canadensis). Prevalence was highest in polar bears and wolverines, while intensity (larvae per gram, LPG) was highest in red foxes, arctic foxes, and wolves. Most animals (65%) harbored single infections with Trichinella nativa, followed by mixed infections of T. nativa and Trichinella T6 (33%). A single wolverine was infected with T. nativa, T6, and T. chanchalensis. Combining NGS with statistical methods, we found no evidence of competition between T. nativa and T6 in host muscles. Trichinella spp. infection (primarily T. nativa) was the highest in the Northwestern region, whereas T6 infection probability was higher in the Interior and Southern regions, suggesting differences in environmental resistance even among these three taxa. In a single, highly infected brown bear, we detected a rare case of Trichinella spiralis of foreign origin based on whole-genome sequencing, suggesting illegal importation and disposal of meat.

CONCLUSIONS: We report a new geographical record for T. chanchalensis and a rare finding of T. spiralis in North American wildlife, and demonstrate the utility of new NGS methods for describing the ecology of parasites maintained in wildlife hosts commonly presenting as co-infections.

PMID:41372994 | DOI:10.1186/s13071-025-07142-x

Genome Med. 2025 Dec 10. doi: 10.1186/s13073-025-01582-x. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) diagnosis relies on identifying disease episodes disseminated in space and time, and excluding other disease explanations. MS is a genetically complex autoimmune and neurodegenerative disorder that shares features with some monogenic progressive neurological conditions. The extent to which people diagnosed with MS have an alternate diagnosis (MS mimic), or genetic multimorbidity is unknown. Additionally, the burden of rare variation associated with MS risk and severity in monogenic neurological disease genes has not been evaluated. We investigated the prevalence of disease-causing variants in progressive neurological disease genes, and their contribution to MS risk and severity, in 4,340 MS cases diagnosed in sub-speciality clinics in Australia and New Zealand, and in 2,861 local controls.

METHODS: Exome sequencing and array-based genotyping data were analysed for 1,680 genes with pathogenic or likely pathogenic variants reported in ClinVar. Clinical history reviews of MS cases with putative disease-causing variants were conducted. We specifically examined the contribution of rare, likely deleterious variants in a subset of 30 hereditary spastic paraplegia (HSP) genes in 421 individuals with progressive onset MS (POMS). Gene-based association tests with MS risk and severity were performed for all genes in the cohort.

RESULTS: We identified 166 MS cases (3.82%) with variants prompting clinical history reviews, and of 75 cases reviewed, four (0.13% of all cases) had either genetic multimorbidity in addition to MS or a potential misdiagnosis. In contrast to previous findings we observed no enrichment of likely deleterious variants in HSP genes in POMS, nor did we find significant associations between neurological disease genes and MS risk or severity.

CONCLUSIONS: Our findings suggest that rare deleterious genetic variation in progressive neurological disease genes does not play a substantive role in MS risk or severity, and that misdiagnosis is exceedingly rare in this cohort. Consequently, among individuals diagnosed with MS by a specialist, a very small proportion may benefit from clinical genomic testing to inform MS diagnosis or an alternate diagnosis, which could have implications for healthcare management.

PMID:41372986 | DOI:10.1186/s13073-025-01582-x