Citations

Abstract Background In randomized clinical trials (RCTs), anticipating control arm outcomes is important for power calculations and enrollment goals. Unexpected overperformance of the control arm can underpower RCTs. The objective of this study was to estimate the prevalence of control arm overperformance in phase 3 oncology RCTs. Methods The authors conducted a meta‐epidemiological study of two‐arm, superiority‐design, phase 3 oncology RCTs. They reviewed articles/publications and protocols for power calculations, justification, and outcomes. Control arm performance was measured as the ratio of observed control arm outcomes relative to pretrial estimates, and overperformance was defined as a 10% improvement. Results In total, 385 RCTs met inclusion criteria. The primary end point was overall survival (OS) in 134 RCTs (35%). Of 311 RCTs (81%) that provided a pretrial estimate for control arm performance, 138 RCTs (44%) cited a justification for the estimate. Greater than expected control arm performance was associated with lower odds of meeting the primary end point (adjusted odds ratio, 0.989; 95% confidence interval, 0.981–0.998; p = 0.015). Of 244 RCTs that were evaluable for control arm performance, 104 (43%) exhibited overperformance. RCTs that used OS as a primary end point were more likely to exhibit control arm overperformance compared with RCTs that used other primary end points (56% vs. 33%; adjusted odds ratio, 2.43; 95% confidence interval, 1.42–4.15; p = .001). Conclusions Control arm overperformance is common in phase 3 oncology RCTs and is associated with trial outcomes, suggesting an effect on study power. Because overperformance appears to be especially prevalent when OS is the primary end point, the effects of postprogression therapies on OS may be underappreciated. Alternative strategies for designing trials should be considered for reliable estimation of treatment effects.

Abstract Aims Artificial intelligence electrocardiography (AI-ECG) algorithms are emerging tools for identifying individuals at risk of atrial fibrillation (AF). We evaluated the predictive performance of a validated AI-ECG algorithm for incident AF in UK Biobank participants with AF risk factors, irrespective of prevalent cardiovascular disease, and its incremental value when added to clinical predictors. Methods and results The AI-ECG tool was applied to sinus rhythm ECGs from UK-Biobank participants with risk factors for AF but no AF. Model performance was evaluated using time-dependent ROC-AUC and Harrell’s C-index. Multivariable Cox regression was used to identify clinical risk factors associated with incident AF and to quantify the contribution of AI-ECG. A total of 21 842 participants (56% male) were included. The median follow-up time was 3.7 years (IQR 0.5–5.4) The ECG-AI tool achieved a ROC-AUC of 0.73 (95% CI 0.68–0.78) at 1 and 0.69 (95% CI 0.66–0.72) at 3 years. A multivariable Cox regression model using clinical parameters achieved a ROC-AUC of 0.71 (95% CI 0.66–0.75) at 1 and 0.71 (95% CI 0.68–0.74) at 3 years. By adding ECG-AI to the clinical Cox regression model, the ROC-AUC increased to 0.75 (95%CI 0.71–0.80) at 1 and 0.74 (95% CI 0.71–0.77) at 3 years. AI-ECG showed a hazard ratio of 1.23 per decile increase (95% CI 1.18–1.27). Conclusion An AI-ECG algorithm improved the prediction of incident AF when added to a clinical parameter-based model over a median follow-up time of 3.7 years among individuals with comorbidities predisposing to AF who may benefit from targeted screening and preventive strategies.

ABSTRACT Background Sentinel lymph node (SLN) biopsy is a critical staging tool in skin and soft tissue cancers. Although technetium lymphoscintigraphy is the most common adjunct, indocyanine green (ICG) demonstrates a promising alternative in pediatric, adolescent, and young adult (AYA) skin and soft tissue cancers. Methods and Objectives Evaluate the safety and efficacy of ICG in SLN biopsy (SLNB) in diverse pediatric and AYA solid cancers in a multi‐institutional environment. This is a prospective, observational study conducted at 13 member institutions in the Pediatric Surgical Oncology Research Collaborative between 2019 and 2023. Eligible patients underwent SLNB for primary or recurrent solid skin and soft tissue tumors. Peritumoral ICG was administered intraoperatively. Outcomes included SLN detection rates, histopathology of excised specimens, and surgeon‐reported assessment of utility. Safety was assessed through adverse event reporting. Results Forty SLNB procedures yielded 84 specimens: 13 melanoma (32.5%), 12 squamous cell carcinoma (30%), 11 non‐rhabdomyosarcoma soft tissue sarcoma (27.5%), two rhabdomyosarcoma (5%), one Ewing sarcoma (2.5%), and one malignant peripheral nerve sheath tumor (2.5%). Histologic evaluation identified 81 lymph nodes, 75 benign (89.3%) and six malignant (7.1%); three specimens were adipose tissue (3.6%). Of 81 lymph nodes, 76% were ICG‐positive. ICG had a sensitivity of 79.5%, a specificity of 33%, and a positive predictive value of 96%. All malignant nodes were ICG‐avid. There were no adverse reactions to ICG at 30 days. Conclusions ICG is a safe and effective adjunct for SLNB in pediatric and AYA soft tissue and skin malignancies.

ABSTRACT Fixation constructs used in orthopedic surgery are typically evaluated based on their initial mechanical strength. However, fixation failure often occurs under cyclic loading in dynamic environments where early motion and stress concentration are common. In the foot and ankle, nitonal staples and short locking plates have been developed to maximize construct stiffness and accommodate the limited bony surface area available for fixation. The implants have grown in popularity, but unlike other AO constructs, they have not been rigorously studied across multiple mechanical performance domains. Prior studies have not comprehensively compared dynamic nitinol constructs to static plates and screws across key mechanical performance metrics under fatigue conditions. Six fixation constructs (2‐leg staple, 4‐leg staple, 4‐leg + 2‐leg perpendicular staple, 4‐hole titanium plate, 5‐hole titanium plate with cross‐screw, and 4‐leg staple + dynamic disc + cross‐screw) were evaluated using standardized synthetic bone block models ( n = 5/group). Constructs were subjected to 100 cycles of loading. Pre‐ and post‐cycle values for compression ( N ), contact area (mm²), rigidity ( N ), and torque ( N ·cm) were measured. Paired t‐tests assessed intra‐construct degradation as well as post‐cycle inter‐construct differences. Additionally, ANOVA with Tukey HSD identified inter‐construct differences in degradation. Cohen's d quantified effect sizes. The 4‐leg + 2‐leg perpendicular construct had the highest post‐cycle compression (68.0 N) and contact area (447.2 mm²), with small to moderate degradation (d = –1.38; −0.99); the 4‐hole plate showed the greatest degradation ( p = 0.001, d = −3.48; p < 0.001, d = −4.45). Torque and rigidity degraded most in the 5‐hole plate (Δ = −94.4 N·cm, p = 0.0002, d = −6.21; Δ = −237.4 N, p = 0.015, d = −1.83), while dynamic constructs showed better retention. Dynamic nitinol constructs outperformed static plates and screws across all metrics, especially in preserving compression and contact while also resisting fatigue. Dual‐plane constructs—4‐Leg + 2‐Leg perpendicular and 5‐Hole Plate with Screw—demonstrated 2–3× higher initial rigidity than their single‐plane counterparts and showed superior fatigue resistance. Dynamic nitinol constructs demonstrated superior biomechanical durability compared to static plate‐and‐screw constructs, particularly when used in dual‐plane configurations. These findings support a shift in fixation strategy toward implants that maintain mechanical engagement under physiologic loading. In load‐bearing regions like the foot, fixation constructs must retain strength through repetitive stress. Dual‐plane dynamic nitinol implants provide continuous compression and greater fatigue resistance, making them a compelling alternative to static fixation. Future clinical studies should evaluate their impact on outcomes and hardware failure in early weightbearing protocols.