Category: Statistics

J Orthop Res. 2025 Apr 12. doi: 10.1002/jor.26083. Online ahead of print.

ABSTRACT

Non-governmental educational programs such as the annual Orthopaedic Research and Education Foundation (OREF) Resident Research Symposia aim to elevate and fund trainee research endeavors. This study investigates the translation of research recognized at the Resident Research Symposia into peer-reviewed publication and the rate of awardees who pursue academic careers after training. Awards from the OREF Resident Research Symposia between 2008 and 2023 were aggregated. Characteristics of awardees and projects were noted. Conversion to publication and journal characteristics were identified by indexing major research databases. The current practice type and specialty of each trainee was queried using the American Academy of Orthopedic Surgeons roster and institutional sites. Descriptive statistics, univariate and multivariate regression models were performed. Primary outcomes included rates of OREF symposia presentation conversion to publication and trainees pursuing a career in academia. Three hundred and eighty-nine awards were included with 72 (18.5%) females and 317 (81.5%) males. One hundred and forty-two (36.5%) were first place awards, 101 (25.9%) second place, 131 (33.7%) third place, and 15 (3.9%) presenter’s choice, across five regions. Basic science projects were more likely to win first-place awards (p = 0.001). Awarded projects translated to 300 (77%) peer-reviewed publications, with an average impact factor of 1.78 ± 1.65. Male and first-place awardees were more likely to publish (p = 0.014, p = 0.001). The current practice types of 376 distinct awardees were identified with 149 awardees currently practicing in academia (42.3%). Awardees that successfully published their projects (p < 0.001), and those from the Mid-Atlantic region (p = 0.01) were more likely to pursue academic careers. Research awarded at the OREF symposium translates to peer-reviewed publication at a high rate, and awardees enter academia at a disproportionately high rate. OREF provides an effective platform to identify and support budding surgeon-scientists, which is vital given that musculoskeletal research is historically underfunded at a national level.

PMID:40221869 | DOI:10.1002/jor.26083

Bioinformatics. 2025 Apr 12:btaf171. doi: 10.1093/bioinformatics/btaf171. Online ahead of print.

ABSTRACT

SUMMARY: Statistical methods that measure the extent of haplotype homozygosity on chromosomes have been highly informative for identifying episodes of recent selection. For example, the integrated haplotype score (iHS) and the extended haplotype homozygosity (EHH) statistics detect long-range haplotype structure around derived and ancestral alleles indicative of classic and soft selective sweeps, respectively. However, to our knowledge, there are currently no publicly available methods that classify ancestral and derived alleles in genomic datasets for the purpose of quantifying the extent of haplotype homozygosity. Here, we introduce the Polaris package, which polarizes chromosomal variants into ancestral and derived alleles and creates corresponding genetic maps for analysis by selscan and HaploSweep, two versatile haplotype-based programs that perform scans for selection. With the input files generated by Polaris, selscan and/or HaploSweep can produce the appropriate sign (either positive or negative) for outlier iHS statistics, enabling users to distinguish between selection on derived or ancestral alleles. In addition, Polaris can convert the numerical output of these analyses into graphical representations of selective sweeps, increasing the functionality of our software.

RESULTS: To demonstrate the utility of our approach, we applied the Polaris package to Chromosome 2 in the European Finnish, Middle Eastern Bedouin, and East African Maasai populations. More specifically, we examined the regulatory sequence in intron 13 of the MCM6 gene associated with lactase persistence (ie, the ability to digest the lactose sugar present in fresh milk), a region of intense interest to human evolutionary geneticists. Our analyses showed that derived alleles (at known enhancers for lactase expression) sit on an extended haplotype background in the Finnish, Bedouin, and Maasai consistent with a classic selective sweep model as determined by iHS and EHH statistics. Importantly, we were able to immediately identify this target allele under selection based on the information generated by our software. We also explored outlier statistics across Chromosome 2 in two distinct datasets from these populations: i) one containing polarized alleles generated with Polaris and ii) the other containing unpolarized alleles in the original phased vcf file. Here, we found an excess of outlier statistics on Chromosome 2 in the unpolarized datasets, raising the possibility that a subset of these ‘hits’ of selection may be unreliable. Overall, Polaris is a versatile package that enables users to efficiently explore, interpret, and report signals of recent selection in genomic datasets.

AVAILABILITY AND IMPLEMENTATION: The Polaris package is free and open source on GitHub (https://github.com/alisi1989/Polaris) and on DropBox (https://www.dropbox.com/scl/fo/mlxizft5267vem9u62qkn/AAnM0qX923zPzQBlPX8iteM?rlkey=uezrp4t2waffpj0nmo1evr320&e=1&st=jaodccws&dl=0).

CONTACT: alisi@usc.edu; mc44680@usc.edu.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40221866 | DOI:10.1093/bioinformatics/btaf171

Br J Radiol. 2025 Apr 12:tqaf081. doi: 10.1093/bjr/tqaf081. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to compare 3-minute delayed phase images with 5-minute delayed phase images for quantifying hepatic extracellular volume fraction (ECV) using dual-energy computed tomography (CT).

METHODS: Between January 2020 and July 2022, eighty consecutive patients with chronic liver disease (45 men and 35 women, mean age: 69.3 ± 10.4 years) were included in this study cohort. All patients underwent both 3- and 5-minute delayed phase CT scans for assessing focal liver lesions. ECV value was calculated by the iodine densities of the hepatic parenchyma and aorta, and compared between in each phase. Correlations between ECV values in each phase with the albumin-bilirubin (ALBI) score and grade, fibrosis-4 index (Fib-4), and clinical fibrosis stage were statistically analyzed.

RESULTS: No significant difference was found in ECV values between the 3- and 5-minute delayed phase images (p = 0.056). The ratio of ECV values for 3-minute to 5-minute delayed phase images was 0.984 ± 0.078, ranging from 0.85 to 1.16. The ECV calculated on 3- and 5-minute delayed phase images showed strong and moderate correlations with ALBI grade (Spearman’s ρ; 0.763 and 0.724, respectively) and ALBI score (Spearman’s ρ; 0.707 and 0.668, respectively), and also showed moderate correlations with Fib-4 (Spearman’s ρ; 0.548 and 0.543, respectively) and clinical fibrosis stage (Spearman’s ρ; 0.468 and 0.435, respectively).

CONCLUSION: Three-minute delayed phase images were found to be equivalent to 5-minute delayed phase images for the calculation of ECV.

PMID:40221863 | DOI:10.1093/bjr/tqaf081

Rheumatology (Oxford). 2025 Apr 12:keaf207. doi: 10.1093/rheumatology/keaf207. Online ahead of print.

ABSTRACT

OBJECTIVES: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease in which a significant proportion of patients remain refractory to existing therapies. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiated a project aimed at unraveling the reasons for treatment failures in PsA, culminating in the establishment of definitions for Difficult-to-Treat PsA (D2T-PsA) and Complex-to-Manage PsA (C2M-PsA). This study explores patient perspectives on treatment-resistant PsA, incorporating a broader patient perspective into the overarching GRAPPA project.

METHODS: Multilingual (10 languages), online survey to explore PsA patients’ perspectives on treatment inefficacies. Developed collaboratively by GRAPPA members and patient research partners. It included sections on demographic data, structured questions about treatment failures, and open-ended questions. Data analysis used descriptive statistics and inductive coding of qualitative responses via Dedoose.

RESULTS: Among 570 respondents, most were female (68.8%) and White (72.6%), with an average PsA diagnosis delay of 4.3 years. Key contributors to D2T- and C2M-PsA were persistent joint pain and psoriasis (65.7%), fatigue (52.8%), and medication side effects (41.7%). Ranked by impact, arthritis was the most debilitating symptom. Quality of life concerns were notable, with sleep impairment and reduced life enjoyment being reported by 66.4%. Language differences emerged; for instance, with Dutch and Italian respondents prioritizing fatigue and daily life impact, respectively.

CONCLUSION: This is the first international study to highlight patient-driven insights in the management of resistant PsA, emphasizing a multidimensional approach that considers biological and psychosocial factors. These insights will inform the ongoing GRAPPA initiative to standardize definitions for treatment-resistant PsA, ultimately improving patient care.

PMID:40221862 | DOI:10.1093/rheumatology/keaf207

Eur J Cardiothorac Surg. 2025 Apr 12:ezaf139. doi: 10.1093/ejcts/ezaf139. Online ahead of print.

ABSTRACT

Trials in cardiac surgery are often hampered at the design level by small sample sizes and ethical considerations. The conventional analytical approach, combining frequentist statistics with null hypothesis significance testing, has known limitations and its associated p-values are often misinterpreted, leading to dichotomous conclusions of trial results. The Bayesian statistical framework may overcome these limitations through probabilistic reasoning, and is subsequently introduced in this Primer. The Bayesian framework combines prior beliefs and currently obtained data (the likelihood), resulting in updated beliefs, also known as posterior distributions. These distributions subsequently facilitate probabilistic interpretations. Several previous cardiac surgery trials have been performed under a Bayesian framework and this Primer enhances the understanding of their basic concepts by linking results to graphical presentations. Furthermore, contemporary trials that were initially analysed under a frequentist framework, are re-analysed within a Bayesian framework to demonstrate several interpretative advantages.

PMID:40221858 | DOI:10.1093/ejcts/ezaf139

Mol Ther. 2025 Apr 11:S1525-0016(25)00283-7. doi: 10.1016/j.ymthe.2025.04.009. Online ahead of print.

ABSTRACT

Intramuscular injection of donaperminogene seltoplasmid (recombinant human hepatocyte growth factor plasmids) represents a gene therapy that treat patients with chronic limb-threatening ischemia (CLTI). The HOPE CLTI-2 trial was a Phase 3, multicenter, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of seltoplasmid in patients with Rutherford class 5 CLTI. This study did not require participants to be ineligible for revascularization, allowing enrollment of patients with CLTI caused by either atherosclerosis (ASO) or Buerger’s disease (TAO). The primary endpoint was the complete ulcer healing rate at 6 months. A total of 242 participants (53.3% ASO versus 46.7% TAO) were enrolled, with 161 receiving seltoplasmid and 81 receiving placebo. Complete ulcer healing was achieved in 70 patients in the seltoplasmid group compared to 15 patients in the placebo group, resulting in an adjusted healing rate difference of 26.1% (95% confidence interval [CI]: 15.1-37.0%; P < 0.001). The hazard ratio for healing was 2.31 (95% CI: 1.32-4.05; P = 0.004). The benefits of seltoplasmid on ulcer healing persisted in both TAO and ASO subgroups. Serious adverse events were rare. Our study demonstrated that seltoplasmid significantly improved ulcer healing rates in patients with Rutherford class 5 CLTI compared to placebo.

PMID:40221835 | DOI:10.1016/j.ymthe.2025.04.009

Perfusion. 2025 Apr 12:2676591251328856. doi: 10.1177/02676591251328856. Online ahead of print.

ABSTRACT

AimThis study evaluates the accuracy of a newly derived blood volume estimation formula based on the Boer equation for lean body mass, comparing its performance against the Nadler, Allen and Lemmens-Bernstein-Brodsky formulas.MethodsBlood volume estimation was evaluated using two datasets: the Retzlaff dataset, based on 78 healthy individuals, and the Allen dataset, derived from 81 subjects, two of European descent, the remainder Chinese ‘medical, nursing and pedagogic students, technicians, clerks and family members’ and one young Chinese physician. The formulas were compared using robust statistical methods, including the Wilcoxon Signed-Rank Test, permutation tests, Bland-Altman analysis, and Proportion Within Range.ResultsAcross all methods, the formula derived from the Boer equation showed the narrowest limits of agreement and smallest variability in most metrics, highlighting its potential as the most accurate and clinically useful tool for blood volume estimation. The Nadler formula also performed well but with slightly larger errors and bias.ConclusionThis study highlights the limitations of the Allen formula and demonstrates the superior performance of the Boer formula, which is derived from lean body mass. While the Allen formula performed well on its original dataset, it showed higher variability and less accuracy on more modern data. Both the Nadler and Boer formulas exhibited greater precision, with the Boer formula showing slightly lower variability. The study emphasizes the importance of using independent data sets for validation and addresses a critical gap in blood volume assessment by using robust techniques for analysis.

PMID:40221826 | DOI:10.1177/02676591251328856

BMC Pharmacol Toxicol. 2025 Apr 12;26(1):82. doi: 10.1186/s40360-025-00902-6.

ABSTRACT

BACKGROUND: Faricimab is a bispecific antibody targeting vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), offering a novel therapeutic approach for ocular diseases. However, its long-term safety profile remains under evaluation. This study analyzes its adverse events (AEs) using the U.S. FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER).

METHODS: AEs from FAERS (2004-2024) and JADER (2004-2024) were analyzed using disproportionality algorithms. Subgroup analyses assessed differences by age and sex. AE onset time was also assessed.

RESULTS: Several newly identified adverse events (AEs) were observed, including macular ischemia, keratic precipitates, and optic nerve injury, with strong safety signals detected in both FAERS and JADER. For instance, macular ischemia showed a high association with faricimab use (ROR = 260.46), suggesting a potential risk of retinal circulation impairment. Similarly, keratic precipitates (ROR = 739.65) indicate a notable inflammatory response. All these findings highlight the need for closer monitoring of ocular complications, particularly in high-risk patient groups. The FAERS database mainly reported retinal occlusive vasculitis, ocular vasculitis, and keratic precipitates, while JADER predominantly featured retinal occlusive vasculitis and retinal vascular occlusion. Sex-based differences indicated a higher risk of inflammatory AEs in females (e.g., uveitis and eye inflammation) and a greater incidence of retinal vascular events in males (e.g., retinal vasculitis). Age-related differences showed that older patients (≥65 years) had lower inflammatory AE risks but were more prone to optic nerve damage and retinal atrophy, while younger patients (<65 years) exhibited a higher risk of vitreous hemorrhage and cataracts.

CONCLUSIONS: This study identified previously unreported safety signals, suggesting the need for potential updates to faricimab’s safety labeling. Faricimab’s dual-target mechanism presents unique safety concerns. Clinicians should monitor ocular inflammation and vascular complications, particularly in younger males and Asian patients. Further studies using real-world data are needed to validate these findings.

PMID:40221797 | DOI:10.1186/s40360-025-00902-6

Cardiooncology. 2025 Apr 12;11(1):37. doi: 10.1186/s40959-025-00335-4.

ABSTRACT

INTRODUCTION: Cardiotoxic, anthracycline-based therapies have high value in selected patients with breast cancer. We aimed to describe the effect of anthracycline plus taxane and single taxane chemotherapies on echocardiographic parameters in women with breast cancer.

METHODS: We retrospectively analysed data of 68 women (> 18 years old) treated for breast cancer in 2018-2021 in the Cardiology Outpatient Clinic of Semmelweis University, Department of Internal Medicine and Oncology. Cardiovascular medical history was collected at baseline and transthoracic echocardiography was completed at each visit. Also, we reviewed electronic medical records for other relevant medical information. Measured echocardiography parameters were assigned to five periods (0-14 days, then every half year and beyond day 545) based on the time since the first treatment. Trajectories of ejection fraction and diastolic function associated markers over the follow-up periods were analysed by linear mixed models.

RESULTS: Mean age of the anthracycline plus taxane group was 52.7 ± 14.1 years, of the single taxane group 55.2 ± 13.1 years. The mean anthracycline dose was equivalent to 240 mg/m² of doxorubicin. Overall pre-existing cardiovascular burden was low. Statistically significant changes were found only in the anthracycline plus taxane group: ejection fraction decreased mildly from 65.5 ± 3.1% at baseline to 62.1 ± 3.2% at 181-365 days (p = 0.007) while deceleration time decreased mildly from 227.9 ± 33.9 msec to 197.4 ± 29.4 msec at 15-180 days (p = 0.028). Both drops were only temporary and values neared baseline values over follow-up (p = NS vs. baseline). Other important determinants of ejection fraction were age and hypertension among the investigated risk factors.

CONCLUSION: Our study confirms the overall safety on cardiac function of both single taxane and anthracycline plus taxane chemotherapy, as we found no changes in echocardiographic parameters associated with single taxane therapy, while anthracycline plus taxane chemotherapy was associated with a temporary and clinically insignificant reduction of ejection fraction and deceleration time over 1.5 years of follow-up. Our study is limited by its retrospective nature and the low number of participants.

PMID:40221795 | DOI:10.1186/s40959-025-00335-4

Reprod Health. 2025 Apr 12;22(1):52. doi: 10.1186/s12978-025-02002-4.

ABSTRACT

INTRODUCTION: Prior research suggested that liberation of abortion laws in Sub-Saharan Africa (SSA) was associated with fewer abortion complications and deaths. However, few studies have examined the association of abortion law liberalization with modern contraceptive use and fertility rates among women in SSA. In this study, we assessed the impact of Kenya’s 2010 abortion law liberalization on modern contraceptive use and number of recent births (births in the past 5 years ) among women of reproductive age in Kenya.

METHODS: Data from three rounds of the Demographic and Health Surveys (2003-2016) for Kenya, Tanzania and Uganda were used for the analysis. We used the differences-in-differences estimator to assess the impact of the policy change in Kenya using Tanzania and Uganda as the control group. We performed multivariable logistic and Poisson regressions to estimate the adjusted odds ratios (aOR) and adjusted prevalence rate ratios (aPRR) with 95% confidence interval (CI) for modern contraceptive use and number of recent births respectively.

RESULTS: A weighted sample of 117,163 women aged 15-49 years was used for the analyses. Modern contraceptive use increased from 25.4% and 19.4% to 39.1% and 27.2% for the intervention and control groups, respectively, in the post-intervention period. In contrast, the mean number of recent births declined from 0.71 and 0.88 to 0.63 and 0.80 for the intervention and control group, respectively in the post-intervention period. We found that Kenya’s 2010 abortion law liberalization was associated with more people using modern contraception (aOR, 1.22; 95% CI 1.11, 1.34) and fewer recent births (aPRR, 0.95; 95% CI 0.91, 0.98).

CONCLUSION: Our findings suggest that Kenya’s 2010 abortion law was surprisingly associated with higher use of modern contraceptives. Reforming restrictive abortion laws may indirectly improve use of contraceptives in Sub Saharan African countries.

PMID:40221794 | DOI:10.1186/s12978-025-02002-4