Category: Statistics

Int J Gynecol Cancer. 2026 May 12;36(7):104755. doi: 10.1016/j.ijgc.2026.104755. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the accuracy of ultrasound in identifying residual cervical tumors following conization, using histology as the gold standard.

METHODS: This retrospective, single-center study included patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics IA1-IB1 and early IB2) who underwent conization followed by secondary surgical treatment (re-conization, hysterectomy, or trachelectomy). Patients with locally advanced disease were excluded. All patients underwent trans-vaginal or trans-rectal ultrasound after conization and before definitive surgery between January 2015 and May 2025. Ultrasound findings were classified as follows: a) absence of residual tumor, b) presence of residual tumor, or c) uncertain (suggestive of either residual disease or post-conization artifacts). For statistical analysis, uncertain cases were conservatively considered positive for residual disease. Additionally, a secondary analysis was performed in which “uncertain” cases were classified as negative. Ultrasound results were compared with final histopathology, and diagnostic performance metrics with 95% confidence intervals were calculated.

RESULTS: A total of 166 patients were included (mean age, 44.4 ± 9.2 years). Residual tumor was found at final histology in 75 patients (45.2%), while 91 (54.8%) had no residual disease. The median tumor diameter at conization was 9.8 ± 6.2 mm, and the mean interval between conization and ultrasound was 61.2 ± 45.5 days. Ultrasound correctly identified residual tumor in 40/75 cases (53.3%), while false-positive findings occurred in 16/91 patients (17.6%). Uncertain ultrasound findings were reported in 43 cases (25.9%), of which 16 (37.2%) had residual disease at histology. Residual tumors were predominantly hypoechoic and showed moderate (45.0%) or rich (35.0%) vascularization on color Doppler imaging. Ultrasound demonstrated a sensitivity of 74.7% (95% confidence interval 64.8 to 84.5), specificity of 52.7% (95% confidence interval 42.5 to 63.0), and overall accuracy of 62.7% (95% confidence interval 53.1 to 72.2).

CONCLUSIONS: This study shows that ultrasound has sub-optimal performance in detecting residual tumor after conization for cervical cancer, indicating that optimal timing and accurate assessment of residual disease remain clinically relevant challenges.

PMID:42235121 | DOI:10.1016/j.ijgc.2026.104755

J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Jun 1;1281:125167. doi: 10.1016/j.jchromb.2026.125167. Online ahead of print.

ABSTRACT

Trimethylamine N-oxide (TMAO) is increasingly recognized for its role in the pathogenesis and progression of cardiovascular and metabolic diseases by disturbing fatty acid metabolism. Concurrently, the acylcarnitine profile serves as a critical indicator of associated mitochondrial dysfunction. However, present ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methodologies often focus on a few targets such as betaine, choline, TMAO, and trimethylamine and lack the integrated capability to monitor simultaneous changes in the acylcarnitine profile. This analytical gap restricts the depth of toxicological investigations into the effects of environmental pollutants as well as the thorough assessment of metabolic homeostasis. In this study, an optimized UPLC-MS/MS method was developed for the simultaneous measurement of TMAO and its 15 related metabolites in human serum. Serum samples underwent pretreatment through targeted ethyl bromoacetate-derivatization and protein precipitation. Using 4% bovine serum albumin as a surrogate matrix, matrix-matched calibration was performed to reduce matrix effects and ensure analytical accuracy. Using 10 mmol/L ammonium formate (pH 4.0) and acetonitrile containing 0.1% formic acid as mobile phases, chromatographic separation was achieved on a HILIC column within a 5.5 min runtime. Positive electrospray ionization and multiple reaction monitoring mode were used to monitor the target analytes. The assay demonstrated good linearity (R² > 0.992) with limits of detection ranging from 0.012 to 5.2 μg/L. Spike recoveries in real samples were 84.5%-114.9%, with relative standard deviations below 10%. In conclusion, this study presents a rapid and validated UPLC-MS/MS method for simultaneous profiling of a targeted panel of TMAO, its precursors, and functionally related acylcarnitines in human serum. It may support studies investigating their associations with cardiometabolic disorders, chronic kidney disease, and metabolic dysfunction linked to gut microbial metabolism.

PMID:42235119 | DOI:10.1016/j.jchromb.2026.125167

Neurotherapeutics. 2026 Jun 3;23(4):e00936. doi: 10.1016/j.neurot.2026.e00936. Online ahead of print.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the spread of muscle weakness across body regions. ROCK-ALS was a multicenter, placebo-controlled phase 2 trial assessing the safety, tolerability, and efficacy of the Rho kinase inhibitor fasudil in ALS patients. A key exploratory objective was to evaluate fasudil’s effect on the spread of muscle weakness using the Motor Unit Number Index (MUNIX), an established, quantitative electrophysiological biomarker of lower motor neuron integrity. MUNIX was assessed in 10 muscles at baseline, day 26, day 90, and day 180. In the present post-hoc analysis, correlations were assessed between baseline serum biomarkers-neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)-and baseline clinical measures (ALSFRS-R, slow vital capacity, and MUNIX-10 sum scores) as well as their monthly rates of change, to explore potential prognostic relationships. For the analysis of disease spreading, muscles were classified as newly affected based on MUNIX decline relative to contralateral values or prior measurements, using thresholds of ≥10%, ≥20%, or ≥30%. Out of 118 participants included in the intention-to-treat population, 78 had full MUNIX datasets at baseline, and 67 had at least one follow-up. Baseline MUNIX-10 sum scores correlated with subsequent ALSFRS-R decline, suggesting prognostic value. Additionally, at day 90, fasudil significantly reduced the number of newly affected muscles compared to placebo in a dose-dependent manner over different thresholds. This supports MUNIX as a sensitive biomarker for monitoring disease spreading and demonstrates that fasudil may attenuate the progression of lower motor neuron involvement in ALS. Trial registration number: NCT03792490 (ClinicalTrials.gov); 2017-003676-31 (Eudra-CT).

PMID:42235092 | DOI:10.1016/j.neurot.2026.e00936

Clin Breast Cancer. 2026 Jun 3;26(6):83-88. doi: 10.1016/j.clbc.2026.04.018. Online ahead of print.

ABSTRACT

INTRODUCTION: Li-Fraumeni syndrome increases the risks of multiple cancers, including early-onset breast cancer (BC). At The University of Texas MD Anderson Cancer Center, we aimed to describe the complete cancer histories of women with BC and LFS.

METHODS: Patients with BC and LFS were identified from a prospective BC database between 2001 and 2024. We described their cancer histories, BC characteristics, and genetic testing patterns. Summary statistics and statistical methods for associations between factors of interest were generated.

RESULTS: Ninety-six women were identified with a history of BC and LFS. Among 96 women, 127 breast tumors were diagnosed, and 29% (28/96) of women developed at least 2 BCs. Individuals had histories of 1-7 total cancers, totaling 226 cancers in the cohort; 56% of individuals (54/96) had at least 1 other cancer besides BC. BC was the first cancer diagnosis in 67% (36/54) of patients. More than half of the women (54%) underwent genetic testing after developing at least 2 cancer diagnoses. Radiation-induced malignancies occurred in 26% of patients who received radiation treatment.

CONCLUSIONS: Genetic testing for LFS often occurred after the diagnosis of multiple primary malignancies; therefore, earlier genetic testing for LFS may reduce patients’ cancer burden owing to increased screening and/or prevention. Treatment-related malignancies were high in this population and contribute to the importance of early LFS diagnosis. These observations contribute to the greater understanding of a rare but high-risk cancer syndrome and highlight opportunities for early intervention and prevention that may reduce the cancer burden among women with LFS.

PMID:42235091 | DOI:10.1016/j.clbc.2026.04.018

J Emerg Med. 2026 Apr 30;87:14-30. doi: 10.1016/j.jemermed.2026.04.022. Online ahead of print.

ABSTRACT

BACKGROUND: Undifferentiated agitation in older adults is common in the prehospital setting, and in transitions from emergency medical services (EMS) to emergency department care. Restraints are commonly used in the management of agitation, although there is little evidence to inform the development of best practices.

OBJECTIVES: To explore paramedic experiences and determine perceptions on issues when managing older adults with agitation and using restraints in EMS.

METHODS: We conducted a descriptive cross-sectional survey of paramedics in Alberta, Canada, with a mix of multiple choice and open-ended questions that were interpreted using descriptive statistics and a qualitative thematic analysis, respectively.

RESULTS: Paramedics (n = 162) reported that older adults were commonly restrained due to risk of harm to self (81.5%) or others (76.5%), combative behavior (73.5%), or resistance to care (58.0%). Most paramedics believed that restraints were effective in facilitating care (76.9%) and had not resulted in adverse events (72.8%). Only 44.5% believed they had the necessary training to provide restraint alternatives, however, 93.6% agreed they have de-escalated situations without restraints, and 80.0% felt capable of using non-restraint-based agitation management strategies. Nearly half endorsed having suffered physical injury from patient agitation (48.1%). The mean total moral injury score was 20.9 ± 6.8 (range 9-35), indicating a relatively high level of moral injury.

CONCLUSION: Restraints are frequently used by EMS for the management of agitation among older adults, especially when there was a perceived risk of harm. Physical and moral injury is high among paramedics, as well as insufficient training regarding restraint alternatives.

PMID:42235087 | DOI:10.1016/j.jemermed.2026.04.022

J Med Internet Res. 2026 Jun 3;28:e78568. doi: 10.2196/78568.

ABSTRACT

BACKGROUND: Informal caregivers of people with dementia frequently experience substantial psychological burden, including elevated stress and depressive symptoms. eHealth interventions have emerged as a scalable solution to support caregivers. However, their effectiveness and the influence of intervention characteristics remain unclear.

OBJECTIVE: This study aimed to evaluate the effectiveness of eHealth interventions in reducing caregiver burden and depressive symptoms among informal caregivers of people with dementia, and to explore potential moderators of intervention effectiveness, including delivery modality, human support, and intervention duration.

METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Search extension) guidelines. Eight electronic databases and clinical trial registries were searched from inception to March 10, 2026. Eligible studies were randomized controlled trials involving informal caregivers of people with dementia receiving interactive eHealth interventions compared with usual care or inactive controls. Study selection, data extraction, and risk-of-bias assessment were conducted independently by 2 reviewers (ML and JXR). Meta-analyses were conducted using a random-effects model with the Hartung-Knapp-Sidik-Jonkman adjustment. Heterogeneity was assessed using the I2 statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was evaluated using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) criteria.

RESULTS: Thirty-five trials (N=3388) were included. eHealth interventions were associated with a statistically significant reduction in caregiver burden (k=35, standardized mean difference [SMD] -0.26, 95% CI -0.42 to -0.10; P=.002; τ2=0.16, τ=0.40; 95% PI -1.10 to 0.58) and a modest reduction in depressive symptoms (k=23, SMD -0.27, 95% CI -0.53 to -0.01; P=.04; τ2=0.31, τ=0.55; 95% PI -1.45 to 0.91). While average effects were statistically significant, wide PIs indicate substantial between-study heterogeneity and variability in real-world effectiveness. Subgroup analyses suggested that short-term (≤8 weeks) intervention was associated with borderline significantly stronger effects for caregiver burden, while human-supported and mobile-based interventions demonstrated larger point estimates with substantial heterogeneity. Meta-regression indicated that caregiver age was a potential moderator (P=.05) in univariate analysis, with decreasing effectiveness observed in older populations. Sensitivity analysis of 27 high-quality studies confirmed robust effects (SMD -0.31, P=.002). No significant small-study effects were detected (Egger test: P>.35). The overall certainty of evidence was moderate.

CONCLUSIONS: eHealth interventions provide modest but variable benefits in reducing burden and depressive symptoms among informal caregivers of people with dementia. This review is timely, given the rapidly expanding digital dementia care and extends prior evidence using a more conservative Hartung-Knapp-Sidik-Jonkman framework with PIs, showing that effects vary from minimal to substantial. While average effects support effectiveness, wide PIs and moderate certainty evidence indicate that outcomes are context-dependent and influenced by heterogeneity and methodological limitations. Hybrid digital-human models should be prioritized to enhance consistency and real-world impact.

PMID:42235069 | DOI:10.2196/78568

JMIR Cancer. 2026 Jun 3;12:e82210. doi: 10.2196/82210.

ABSTRACT

BACKGROUND: Despite the human papillomavirus (HPV) vaccine being available to males for the past 12 years, adolescent males continue to lag in HPV vaccine uptake due to a variety of factors. With the ubiquitous nature of social media use among this population, further research is needed to improve HPV vaccine confidence among young adolescent males using these platforms.

OBJECTIVE: Using the Elaboration Likelihood Model (ELM), this study sought to better understand knowledge, attitudes, and beliefs about HPV and HPV vaccination among male adolescents aged 14-17 years and examine how social media messaging influences vaccine perceptions and explore the characteristics of persuasion and trustworthiness of digital content narratives across age and vaccination status.

METHODS: The study team recruited 18 adolescent males to participate in a series of online focus groups and interviews stratified by age (14-15 years and 16-17 years) and HPV vaccination status. The study team worked with our in-house national probability survey panel, AmeriSpeak Teen Panel, to recruit for the discussion groups and interviews. All discussions were recorded, transcribed, and coded using NVivo 14 (Lumivero). ELM was used to develop discussion guides, codebook, and analysis. Emergent themes were identified, and the full team participated in double-coding and analysis. Data were analyzed using rigorous thematic analysis to identify patterns across groups.

RESULTS: Knowledge of HPV varied by age and vaccination status. Older, vaccinated adolescents were more likely to understand that HPV affects both genders and is sexually transmitted, whereas younger, unvaccinated adolescents often had little to no prior awareness. Parents-especially mothers-were the primary decision-makers for vaccinated adolescents, with older adolescents more likely to be engaged in that decision. Trust in social media health messages was low overall, with participants relying on perceived source credibility over content format or style. Trusted sources included parents, physicians, and well-known health organizations. Younger adolescents were more influenced by personal anecdotes, whereas older adolescents preferred statistics, facts, and reliable sources.

CONCLUSIONS: Our findings highlight the importance of tailoring HPV vaccine messaging by age and developmental stage. Trusted messengers, clear factual content, and platform appropriateness are critical for engaging adolescent males. ELM provides a useful lens for interpreting these findings: younger adolescents were more influenced by peripheral cues, personal stories, or visual appeal, whereas older adolescents engaged in more central processing, evaluating the credibility of the source and the factual content of the message. This underscores the need to match message strategies with adolescents’ cognitive and motivational readiness. Future interventions should consider dual strategies targeting both youth and parents, especially for younger adolescents. As the digital landscape continues to evolve, further research should also examine how generative artificial intelligence (AI) may serve as a trusted source or tool for communicating accurate, engaging health information to adolescent audiences.

PMID:42235061 | DOI:10.2196/82210

JMIR Res Protoc. 2026 Jun 3;15:e97781. doi: 10.2196/97781.

ABSTRACT

BACKGROUND: Approximately 80% of individuals with Parkinson disease (PD) experience impaired balance and mobility, contributing to freezing of gait, an increased risk of falls, and reduced health-related quality of life. Mind-body interventions, such as mindfulness and yoga, may address both motor and nonmotor symptoms by enhancing mind-body coordination and reducing stress, thereby offering a scalable approach to balance rehabilitation in PD.

OBJECTIVE: This study aims to evaluate the effects and acceptability of Mindfulness Yoga-Practice Awareness through Cognitive-Based Exercise (MY-PACE), a mobile health-delivered, home-based intervention, on balance, mobility, and psychological well-being in individuals with PD and balance impairment.

METHODS: This assessor-blinded, 2-arm, randomized waitlist-controlled trial enrolled 132 individuals with PD and balance impairment, randomized to either the MY-PACE group (n=66, 50%) or the control group receiving routine outpatient care (n=66, 50%). The MY-PACE group will complete a 12-week, Zoom-delivered program incorporating mindfulness, yoga, and mindful walking practices. The control group will receive the intervention after study completion. The primary outcome is functional balance, as measured by the Berg Balance Scale. Secondary outcomes include functional mobility, gait patterns, balance confidence, freezing of gait severity, motor symptoms, anxiety and depressive symptoms, cognitive function, mindfulness, health-related quality of life, and fall incidence. Assessments will occur at baseline, 3 months (T1), and 6 months (T2). Data will be analyzed using linear mixed-effects models under the intention-to-treat principle.

RESULTS: Ethics approval was obtained on September 18, 2019. A preliminary feasibility study with 10 participants was conducted between May and June 2020. The full randomized controlled trial was funded in January 2022 by the Early Career Scheme 2021-2022 of the Research Grants Council, Hong Kong. The trial was prospectively registered on December 10, 2021. Recruitment began in April 2022. As of manuscript submission, 132 participants have been enrolled. Data analysis has not yet commenced. The study protocol and statistical analysis plan follow the original prespecified design. The results are expected to be published in 2026.

CONCLUSIONS: This trial will evaluate a telehealth-delivered mindful yoga intervention for improving balance and mobility in individuals with PD. By integrating cognitive-based mindful awareness and motor training, MY-PACE targets both motor and nonmotor contributors to balance impairment. If effective, it may represent a scalable intervention for individuals with PD and other populations with mobility limitations.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100054145; https://tinyurl.com/4j8f8zvn.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/97781.

PMID:42235054 | DOI:10.2196/97781

J Drugs Dermatol. 2026 Jun 1;25(6):83251s3-83251s10. doi: 10.36849/JDD.83251.

ABSTRACT

Hair loss is a widespread condition with a potentially severe psychological burden, especially among women. The chance of suffering from female alopecia increases with menopause, and topical treatments beyond minoxidil are scarce. Over the past several years, new combinations of natural ingredients and patented mixtures have shown promising results to improve hair shedding, thus helping recover self-esteem and confidence. In this work, results of a prospective, open-label clinical trial conducted in women of predominantly menopausal age provides evidence that the dual cosmetic serum system developed by KilgourMD displays statistically significant and clinically meaningful effects on female hair loss, measured through an objective combing test, modified hair wash test, and clinical expert evaluation, after an application period of 4 months.

PMID:42235052 | DOI:10.36849/JDD.83251

J Drugs Dermatol. 2026 Jun 1;25(6):523-529. doi: 10.36849/JDD.9346.

ABSTRACT

BACKGROUND: Acne is the most prevalent skin disease globally, with a significant burden and limited therapeutic innovation. Although it has a multifactorial etiology, Cutibacterium acnes (C acnes) overgrowth is a key factor in driving inflammation in acne. Bacteriophages are a novel mechanism that can specifically target C acnes and are found in greater abundance on healthy skin compared to acne-prone skin.

OBJECTIVES: To study the safety and efficacy of phages and salicylic acid (SA) in acne, and to analyze their mode of action and effect on microbiome diversity.

METHODS: A randomized double-blind placebo-controlled study was conducted on 90 participants for 8 weeks. Males and females 12 to 35 years old with mild to moderate acne were enrolled in placebo, phage, and phage + SA arms. Clinic visits at baseline, week 4, and week 8 collected safety data, VISIA imaging, lesion counts, IGA scores, and microbiome samples.

RESULTS: Phage treatment demonstrated an excellent safety profile. Participants in both phage and phage + SA arms showed significant improvement (P<0.05) over baseline at 8 weeks. Phage application resulted in a statistically significant (P<0.05) decrease of C acnes on the skin compared to placebo. Notably, phage use over 8 weeks significantly increased microbiome diversity, a marker of long-term skin health.

CONCLUSION: This study shows the potential of bacteriophages to be a highly promising modality with a unique mode of action for the treatment of acne. Beyond short-term lesion improvement, phage-induced enhancement of microbiome diversity suggests potential for durable, long-term skin health benefits. &nbsp.

PMID:42235049 | DOI:10.36849/JDD.9346