Tag: statistics

Pediatr Cardiol. 2025 Jun 14. doi: 10.1007/s00246-025-03923-4. Online ahead of print.

ABSTRACT

Congenital heart disease (CHD) remains a leading cause of neonatal morbidity and mortality. The University of California Fetal Consortium implemented a Standardized Clinical Assessment and Management Plan (SCAMP) to optimize birth timing and mode of birth in pregnancies complicated by fetal CHD. This study evaluates the impact of SCAMP implementation on neonatal outcomes, specifically survival to hospital discharge, birth weight, and hospital length of stay. A retrospective cohort study was conducted comparing neonates with prenatally diagnosed CHD before (historical cohort) and after (intervention cohort) SCAMP implementation. Neonatal data, including mode of birth, birth weight, survival to discharge, and CHD classification was collected from five UC medical centers. Comparative analyses were performed using t-tests for continuous variables and chi-square tests for categorical variables. A total of 414 neonates met inclusion criteria (167 in the historical cohort, 247 in the intervention cohort). The overall neonatal survival rate to discharge was significantly higher in the intervention cohort (91.1% vs. 83.1%, p = 0.04). Survival following cesarean birth was also improved in the intervention cohort (89.1% vs. 78.1%, p = 0.04), while no significant differences were found for induction of labor or spontaneous vaginal births. Birth weight was significantly higher post-SCAMP (2977 g vs. 2838 g, p = 0.01), and hospital length of stay was significantly shorter (11.5 vs. 26 days, p < 0.01). Survival differences by CHD risk classification were not statistically significant. SCAMP implementation was associated with improved neonatal survival, increased birth weight, and reduced hospitalization duration in CHD-affected pregnancies. These findings underscore the importance of standardized perinatal management in optimizing outcomes for neonates with CHD.

PMID:40517188 | DOI:10.1007/s00246-025-03923-4

NPJ Genom Med. 2025 Jun 14;10(1):48. doi: 10.1038/s41525-025-00507-2.

ABSTRACT

Genome-wide association studies (GWAS) have established key role of immune dysfunction in Age-related Macular Degeneration (AMD), though the precise role of immune cells remains unclear. Here, we develop an explainable machine-learning pipeline (ML) using transcriptome data of 453 donor retinas, identifying 81 genes distinguishing AMD from controls (AUC-ROC of 0.80, CI 0.70-0.92). Most of these genes were enriched in their expression within retinal glial cells, particularly microglia and astrocytes. Their role in AMD was further strengthened by cellular deconvolution, which identified distinct differences in microglia and astrocytes between normal and AMD. We corroborated these findings using independent single-cell data, where several ML genes exhibited differential expression. Finally, the integration of AMD-GWAS data identified a regulatory variant, rs4133124 at PLCG2, as a novel AMD association. Collectively, our study provides molecular insights into the recurring theme of immune dysfunction in AMD and highlights the significance of glial cell differences in AMD progression.

PMID:40517179 | DOI:10.1038/s41525-025-00507-2

Eur J Hum Genet. 2025 Jun 14. doi: 10.1038/s41431-025-01891-0. Online ahead of print.

ABSTRACT

Structural variants (SVs) of the nebulin gene (NEB), including intragenic duplications, deletions, and copy number variation of the triplicate region, are an established cause of recessively inherited nemaline myopathies and related neuromuscular disorders. Large deletions have been shown to cause dominantly inherited distal myopathies. Here we provide an overview of 35 families with muscle disorders caused by such SVs in NEB. Using custom Comparative Genomic Hybridization arrays, exome sequencing, short-read genome sequencing, custom Droplet Digital PCR, or Sanger sequencing, we identified pathogenic SVs in 35 families with NEB-related myopathies. In 23 families, recessive intragenic deletions and duplications or pathogenic gains of the triplicate region segregating with the disease in compound heterozygous form, together with a small variant in trans, were identified. In two families the SV was, however, homozygous. Eight of these families have not been described previously. In 12 families with a distal myopathy phenotype (of which 10 are previously unpublished), eight unique, large deletions encompassing 52-97 exons in either heterozygous (n = 10) or mosaic (n = 2) state were identified. In the families where inheritance was recessive, no correlation could be made between the types of variants and the severity of the disease. In contrast, all patients with large dominant deletions in NEB had milder, predominantly distal muscle weakness. For the first time, we establish a clear and statistically significant association between large NEB deletions and a form of distal myopathy. In addition, we provide the hitherto largest overview of the spectrum of SVs in NEB.

PMID:40517164 | DOI:10.1038/s41431-025-01891-0

Eur Arch Otorhinolaryngol. 2025 Jun 14. doi: 10.1007/s00405-025-09512-8. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to evaluate the diagnostic potential of nystagmus direction observed during bow and lean tests (BLTs) in patients with posterior canal canalolithiasis BPPV (P-BPPV), lateral canal canalolithiasis BPPV (Lca-BPPV), and lateral canal cupulolithiasis BPPV (Lcu-BPPV).

METHODS: A total of 62 patients (40 women, 22 men; aged 24-70 years) with clinically suspected BPPV were enrolled. Diagnoses included 39 cases of P-BPPV, 15 of Lca-BPPV, and 8 of Lcu-BPPV. Each participant underwent the Dix-Hallpike Test (DH), Head Roll Test (HRT), and bow and lean tests for diagnostic assessment. The primary outcome was the presence and direction of nystagmus during BLTs, in relation to BPPV subtype.

RESULTS: Nystagmus was detected in 77.4% of subjects during the bow test and in 46.8% during the lean test. A statistically significant difference was found in nystagmus direction across BPPV subtypes (p < 0.05). Right-beating horizontal nystagmus during the bow test was significantly more frequent in right-sided Lca-BPPV. Right down-beating torsional nystagmus during the bow test occurred exclusively in left P-BPPV, while left down-beating torsional nystagmus was seen only in right P-BPPV. Right up-beating torsional nystagmus was significantly associated with right P-BPPV, and left up-beating torsional nystagmus with left P-BPPV (p < 0.05).

CONCLUSIONS: In P-BPPV, DH-induced nystagmus direction was opposite in the bow position but matched in the lean position. These findings underscore the diagnostic value of BLTs, particularly the bow test, in identifying the affected canal in posterior and lateral canal BPPV.

PMID:40517160 | DOI:10.1007/s00405-025-09512-8

Int J Oral Maxillofac Surg. 2025 Jun 13:S0901-5027(25)01327-X. doi: 10.1016/j.ijom.2025.06.007. Online ahead of print.

ABSTRACT

Surgical removal of mandibular third molars is a routine procedure in oral and maxillofacial surgery, often followed by pain, swelling, trismus, and alveolar osteitis (AO), affecting patient comfort and daily function. Platelet-rich fibrin (PRF) is an autologous biomaterial that promotes healing through the gradual release of cytokines and growth factors. This prospective, randomized, controlled, and patient-blinded study investigated whether PRF applied to the extraction socket reduces postoperative symptoms and complications. Ninety patients scheduled for mandibular third molar removal were randomized to receive PRF or no adjunct treatment prior to wound closure. Seventy-five patients completed follow-up and were included in the analysis. Postoperative outcomes including AO, infection, pain, trismus, analgesic use, and sick leave were recorded over 10 days. The incidence of AO was lower in the PRF group (3.0%) compared to the control group (11.9%), although the difference was not statistically significant. PRF treatment significantly reduced postoperative pain during the first six days. These findings suggest that while PRF may not significantly reduce AO incidence, it can contribute to improved patient comfort and recovery by decreasing early postoperative pain.

PMID:40517125 | DOI:10.1016/j.ijom.2025.06.007

Curr Probl Diagn Radiol. 2025 Jun 3:S0363-0188(25)00114-8. doi: 10.1067/j.cpradiol.2025.06.001. Online ahead of print.

ABSTRACT

BACKGROUND: Breast lesions are a common but often missed incidental finding. We evaluated whether artificial intelligence (AI) algorithms can efficiently detect radiologically significant incidental breast lesions (RSIBLs) missed by original interpreting radiologists (OIRs) on chest CT examinations.

METHODS: This retrospective multi-institutional study analyzed chest CT examinations performed in June 2017 by a national teleradiology practice. Visual classifier (VC) and natural language processing (NLP) algorithms flagged potential RSIBLs, which were reviewed independently by two primary readers; disagreements were adjudicated by a third reader. Sizes and margins of confirmed RSIBLs were evaluated similarly. Differences in size and margin obscuration between RSIBLs missed versus identified by OIRs were statistically assessed (alpha, 0.05). A workflow efficiency analysis was performed.

RESULTS: 3279 of 3541 examinations (92.6 %) were marked negative by both algorithms (i.e., VC-/NLP-) and not reviewed. The two primary readers assessed 262 examinations for RSIBLs, with substantial agreement (kappa, 0.77). After adjudication, 76 RSIBLs were confirmed (73 females, 3 males). Compared with the OIRs, the VC algorithm identified more RSIBLs (90.8 % [69/76] vs 39.5 % [30/76]) though with more false positives (67.9 % [178/262] vs. 3.4 % [9/262]). Among the OIRs, missed RSIBLs had smaller diameters than identified RSIBLs (1.4 cm vs. 3.0 cm; P < 0.001). Our reader workflow reduced the number of images viewed by 97.3 % relative to a hypothetical full double-read approach.

CONCLUSION: An AI-based approach enhanced RSIBL detection rates. Although the AI-based approach also increased the number of false positives, our targeted review process allowed for efficient detection of missed RSIBLs.

PMID:40517117 | DOI:10.1067/j.cpradiol.2025.06.001

Epilepsia. 2025 Jun 14. doi: 10.1111/epi.18492. Online ahead of print.

ABSTRACT

OBJECTIVE: Vitamin D has demonstrated potential anticonvulsant effects in experimental and pilot clinical studies; the results of these remain inconclusive. This study aims to investigate the efficacy and safety of adjunctive Vitamin D supplementation in reducing seizure frequency, modulating vitamin D receptor (VDR) activity, and altering the putative biomarkers of epileptogenesis in persons with drug-resistant epilepsy (DRE).

METHODS: This double-blind, placebo-controlled, parallel-group, adjunctive trial recruited patients from a tertiary care hospital in India. Adult persons with DRE and serum Vitamin D levels <30 ng/mL, experiencing ≥2 seizures/month, were randomized (1:1 ratio) to receive either Vitamin D (60,000 IU/week for 3 months, followed by 60 000 IU/month for the next 3 months) or a matching placebo, in addition to their ongoing antiseizure medications. The primary outcome was the percentage change in monthly seizure frequency from baseline to 6 months. Secondary outcomes included 50% responder, serum Vitamin D (25-hydroxycholecalciferol) levels, VDR protein/mRNA expression, putative biomarkers of epileptogenesis (including high-mobility group box protein 1 [HMGB1] and neurotrophin-3 [NT-3]), quality of life, and safety assessment.

RESULTS: Of 200 participants, 99 were in the Vitamin D group and 101 were in the placebo group. No statistically significant difference was observed between the Vitamin D and placebo groups in the primary outcome of percentage change in monthly seizure frequency from baseline after 6 months of intervention (median 33.3, interquartile range [IQR] 0-57.4 vs 16.7, 0-66.7; median estimate 5.5, 95% confidence interval [CI]: -6.7 to 19.2); p = 0.36]. The 50% responder rate was similar between groups (37% vs 35%; odds ratio 1.1, 95% CI: 0.6-1.9; p = 0.68). However, Vitamin D supplementation significantly increased VDR mRNA and protein expression (p < 0.001) and decreased HMGB1 (p = 0.001) and NT-3 (p = 0.002) levels compared to placebo. The recommended serum Vitamin D level (≥30 ng/mL) was achieved in only 36% of subjects in the Vitamin D group. Safety outcomes were comparable between groups.

SIGNIFICANCE: Six months of Vitamin D supplementation at the selected dose did not significantly reduce seizures compared to placebo, potentially due to few persons with DRE achieving recommended serum Vitamin D level (≥30 ng/mL). Significant upregulation of VDR expression and reduction in putative biomarkers of epileptogenesis following Vitamin D supplementation were seen in Vitamin D group despite no corresponding decrease in seizure frequency. This suggests that Vitamin D may have underlying therapeutic effects that warrant further investigation and clinical correlation.

PMID:40516032 | DOI:10.1111/epi.18492

Cancer Control. 2025 Jan-Dec;32:10732748251351105. doi: 10.1177/10732748251351105. Epub 2025 Jun 14.

ABSTRACT

IntroductionEmployment changes among cancer caregivers are common and can result in financial hardship. Lesbian, gay, bisexual, transgender, queer, and other identities outside of cisgender heterosexual (LGBTQ+) individuals are more likely to live in poverty and experience workplace discrimination than non-LGBTQ+ individuals. This study aimed to assess the impact of caregiving-related employment changes and anti-LGBTQ+ stigma on financial hardship and describe lived experiences with financial hardship and related employment changes among LGBTQ+ cancer caregivers.MethodsAn explanatory mixed-methods study was conducted and included a national survey and individual interviews with survey participants. Multivariable logistic regression models were used to test the association of employment changes with financial hardship. An inductive qualitative analysis guided by two of the three domains of financial hardship (ie, material and behavioral) was conducted. Quantitative and qualitative data were integrated throughout the study.ResultsA total of N = 332 LGBTQ+ cancer caregivers participated in the survey, and N = 14 participated in an interview. The average modified COmprehensive Score for financial Toxicity and Caregiver Reaction Assessment financial sub-scale were 25.6 (SD: 9.9, Range: 1-44) and 2.99 (SD: 1.0, Range: 1-5). Employment changes (OR: 3.32, 95% CI: 1.73-6.36) and anti-LGBTQ+ stigma (OR: 2.21, 95% CI: 1.47-3.32) were associated with high financial hardship. Three overarching themes from the qualitative analysis included: 1) Financial Hardship: Increased Costs, Strained Finances, and Lost Wages; 2) Caregiving as an LGBTQ+ Person: Stigma, Outness, and Expectations; and 3) Financial Unmet needs and Recommendations.ConclusionLGBTQ+ cancer caregivers experience substantial financial hardship that is associated with employment changes and anti-LGBTQ+ stigma. LGBTQ + cancer caregivers reported varying levels of outness and acceptance that directly influenced their access to financial support. Cancer-related financial hardship interventions tailored to the needs of LGBTQ+ individuals are needed.

PMID:40516028 | DOI:10.1177/10732748251351105

J Assist Reprod Genet. 2025 Jun 14. doi: 10.1007/s10815-025-03544-z. Online ahead of print.

ABSTRACT

BACKGROUND: Natural cycle in vitro fertilization (NC-IVF) represents a convenient and safe assisted reproductive technology, making it particularly advantageous for patients with poor ovarian response (POR). This research evaluates the effectiveness of NC-IVF for women with POR, aiming to inform personalized treatment decisions.

METHOD: This retrospective cohort study encompassed 13,013 cycles involving women diagnosed with poor ovarian response according to the Bologna criteria. These patients underwent either natural cycles or controlled ovarian stimulation cycles. The primary outcome measure was the cumulative live birth rates, and the secondary outcomes included laboratory and clinical outcomes.

RESULTS: A total of 1073 natural cycles and 11,940 COS cycles were analyzed, with 5956 undergoing low-dose gonadotropin treatment and 5984 receiving high-dose gonadotropin. The basic characteristics were comparable among the three groups. In both fresh and frozen embryo transfer cycles, clinical pregnancy rates, implantation rates, and live birth rates were comparable across all three groups. Furthermore, no statistically significant differences were observed in cumulative live birth rates or time to first live birth between the groups examined. Expenditures in the natural cycle group were substantially lower than those in both COS cohorts. Importantly, further analysis indicated that there were no significant differences among the three groups concerning either pregnancy complications or neonatal outcomes.

CONCLUSION: Our findings indicate that for women demonstrating a poor ovarian response, NC treatment yields comparable pregnancy and live birth rates when compared to controlled ovarian stimulation methods. The natural cycle represents a safe, effective, and economically viable treatment option for this patient population.

PMID:40516010 | DOI:10.1007/s10815-025-03544-z

J Thromb Thrombolysis. 2025 Jun 14. doi: 10.1007/s11239-025-03128-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Clot waveform analysis (CWA) is a technique that continuously monitors changes in light transmittance or absorbance during fibrin clot formation in plasma, enhancing routine clotting test assessment. Patients with Lupus Anticoagulant (LA) and Hemophilia A (HA) both exhibit isolated prolongation of activated partial thromboplastin time (aPTT); however, their management differs significantly. CWA can aid in distinguishing between these conditions, particularly in cases where standard coagulation tests are inconclusive and specialized assays are unavailable.

METHODS: This prospective case-control study included patients with demonstrable LA (n = 69), healthy controls (n = 75) and diseased controls [HA with (n = 16) and without inhibitor (n = 36).

RESULTS: The quantitative data of aPTT-CWA including velocity peak time, acceleration peak time and height of acceleration [-] were significantly lower in LA-positive samples with prolonged aPTT in comparison with HA without inhibitors. The qualitative data comprising Shoulder in 1st derivative, Biphasic wave in 2nd derivative [-] and Serrated wave pattern in 2nd derivative were significantly common in HA samples without inhibitors. In comparison to healthy controls, LA-positive patients with normal aPTT had significantly lower velocity peak time and height of velocity along with higher width of velocity. In acceleration peak time and width of acceleration [-] peak were significantly higher along with lower height of acceleration [+] and height of acceleration [-]. AUROCs of height of acceleration [-], width of acceleration [-] and width of velocity were statistically and biologically significant. The shoulder in 2nd derivative was significantly common in LA-positive samples.

CONCLUSION: The aPTT-CWA has limited utility for differentiating LA positive from HA samples with and without inhibitors. However, aPTT-CWA may help in selecting patients with normal aPTT who merit further confirmatory testing for LA with a compatible history.

PMID:40515980 | DOI:10.1007/s11239-025-03128-9