Subjective Assessment of Eight CT Features in the Prediction of Dysthyroid Optic Neuropathy.

Purpose: To evaluate the subjective assessment of 8 orbital CT features for predicting dysthyroid optic neuropathy (DON).

Methods: Scan montages from 137 orbits without DON and 121 with DON were each graded independently by 3 observers for 8 imaging features: namely, degree of apical crowding, extraocular muscle enlargement, expansion of orbital fat, clarity of the superior orbital fissure, fat prolapse through the superior orbital fissure, medial wall bowing, general orbital vascular congestion, and dilation of the superior ophthalmic vein. Gradings were analyzed individually and also averaged across observers.

Automated High-Content, High-Throughput Spatial Analysis Pipeline for Drug Screening in 3D Tumor Spheroid Inverted Colloidal Crystal Arrays.

High-content, high-throughput (HCHT) screening platforms are essential for drug discovery, yet conventional 2D assays lack physiological relevance, and current 3D spheroid systems often face challenges to scalability, uniformity, and the analytical efficiency required for statistically robust screening. Here, we present a fully integrated 3D HCHT platform that synergizes tumor spheroid arrays generated from a bioinert inverted colloidal crystal (iCC) hydrogel framework with an automated, high-speed image analysis pipeline for rapid and spatially resolved therapeutic profiling. The iCC framework enables spontaneous self-assembly of highly ordered tumor spheroid array at high spheroid density (∼79.

A Bioinert Hydrogel Framework for Precision 3D Cell Cultures: Advancing Automated High-Content and High-Throughput Drug Screening.

Enhanced drug testing efficiency has driven the prominence of high-content and high-throughput screening (HCHTS) in drug discovery and development. However, traditional HCHTS in well-plates often lack complexity of in vivo conditions. 3D cell cultures, like cellular spheroids/organoids, offer a promising alternative by replicating in vivo conditions and improving the reliability of drug responses.

Factors associated with sexually transmitted reinfections, number of sexual partners and condom use among previously infected young people.

BackgroundSexually transmitted infections (STIs) are prevalent in young people. Digital interventions promoting safer sexual behaviours are low-cost and scalable. We use data from a randomised controlled trial of one such potential intervention (safetxt) to investigate factors associated with STI reinfection and risky sexual behaviours.

Timing of surgery for terrible triad of the shoulder: a systematic review.

The terrible triad of the shoulder (STT) is an injury involving anterior shoulder dislocation, rotator cuff tear, and nerve injury. The optimal timing for rotator cuff repair (RCR) remains controversial, with some favoring early intervention and others recommending delaying surgery until nerve recovery. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, exploring STT treatment and RCR timing using PubMed, Embase, and Web of Science.

Reproducibility of the Unaided Subjective Assessment of Orbital Computed X-Ray Tomographic Features in Thyroid Eye Disease.

Purpose: To assess the reproducibility of subjective interpretation of computed x-ray tomography for 8 features associated with thyroid eye disease.

Methods: Patients with confirmed thyroid eye disease had 3 distinct orbital computed x-ray tomography sections presented as anonymized montages to 3 masked observers (#1 orbital radiologist, #2 general radiologist, and #3 orbital surgeon). Eight features were graded: superior orbital fissure clarity, degree of orbital fat prolapse through the superior orbital fissure, loss of fat space at the apex, muscle enlargement, increase in orbital fat volume, vascular congestion, superior ophthalmic vein size, and lamina papyracea bowing.

Pattern Mixture Sensitivity Analyses via Multiple Imputations for Non-Ignorable Dropout in Joint Modeling of Cognition and Risk of Dementia.

Motivated by the Swedish Betula study, we consider the joint modeling of longitudinal memory assessments and the hazard of dementia. In the Betula data, the time-to-dementia onset or its absence is available for all participants, while some memory measurements are missing. In longitudinal studies of aging, one cannot rule out the possibility of dropout due to health issues resulting in missing not at random longitudinal measurements.

Protocol for an adaptive platform trial of intended service user-derived interventions to equitably reduce non-attendance in eye screening programmes in Botswana, India, Kenya and Nepal.

Introduction: Only 30%-50% of people referred to clinics during community-based eye screening are able to access care in Botswana, India, Kenya and Nepal. The access rate is even lower for certain population groups. This platform trial aims to test multiple, iterative, low-risk public health interventions and simple service modifications with a series of individual randomised controlled trials (RCT) conducted in each country, with the aim of increasing the proportion of people attending.

Reference-Based Multiple Imputation for Longitudinal Binary Data.

Introduction: In clinical trials, a treatment policy strategy is often used to handle treatment nonadherence. However, estimation in this context is complicated when data are missing after treatment deviation. Reference-based multiple imputation has been developed for the analysis of a longitudinal continuous outcome in this setting.

Systematic review of shoulder arthroplasty outcomes: what sample size is meaningful?

Background: Shoulder arthroplasty is increasingly performed for shoulder conditions such as arthritis, rotator cuff arthropathy, and traumatic injuries. Registries and other compilations of patient data provide the opportunity to detect meaningful differences in outcomes between alternative techniques and implants. A wide range of outcome measurements are reported after shoulder arthroplasty, but the sample sizes needed to identify meaningful differences have not been studied systematically.

Age, sex and sexual orientation effects in the Safetxt trial: secondary data analysis of a randomised controlled trial.

Background: Increasing rates of sexually transmitted infections (STIs) and antimicrobial resistance among young people underscore the urgent need for preventative interventions. Interventions should be evidence-based and tailored to the unique risks and needs associated with varying age, sex and sexual orientation. We used data from the Safetxt trial to explore whether young people's age, sex and sexual orientation influence (1) their risk of STI reinfection and condom use and (2) the effect of the Safetxt intervention on STI reinfection and condom use.

Surgical Predictors of Clinical Outcome 6 Years After Revision ACL Reconstruction.

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown.

Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient's outcome at 6-year follow-up.

Multiple imputation using auxiliary imputation variables that only predict missingness can increase bias due to data missing not at random.

Background: Epidemiological and clinical studies often have missing data, frequently analysed using multiple imputation (MI). In general, MI estimates will be biased if data are missing not at random (MNAR). Bias due to data MNAR can be reduced by including other variables ("auxiliary variables") in imputation models, in addition to those required for the substantive analysis.

Unleashing the full potential of digital outcome measures in clinical trials: eight questions that need attention.

The use of digital health technologies to measure outcomes in clinical trials opens new opportunities as well as methodological challenges. Digital outcome measures may provide more sensitive and higher-frequency measurements but pose vital statistical challenges around how such outcomes should be defined and validated and how trials incorporating digital outcome measures should be designed and analysed. This article presents eight methodological questions, exploring issues such as the length of measurement period, choice of summary statistic and definition and handling of missing data as well as the potential for new estimands and new analyses to leverage the time series data from digital devices.

Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial.

Background: Motor neuron disease represents a group of progressive and incurable diseases that are characterised by selective loss of motor neurons, resulting in an urgent need for rapid identification of effective disease-modifying therapies. The MND SMART trial aims to test the safety and efficacy of promising interventions efficiently and definitively against a single contemporaneous placebo control group. We now report results of the stage two interim analysis for memantine and trazodone.

Demonstrating the data integrity of routinely collected healthcare systems data for clinical trials (DEDICaTe): A proof-of-concept study.

Healthcare systems data (also known as real-world or routinely collected health data) could transform the conduct of clinical trials. Demonstrating integrity and provenance of these data is critical for clinical trials, to enable their use where appropriate and avoid duplication using scarce trial resources. Building on previous work, this proof-of-concept study used a data intelligence tool, the "Central Metastore," to provide metadata and lineage information of nationally held data.

Digital endpoints in clinical trials: emerging themes from a multi-stakeholder Knowledge Exchange event.

Background: Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people's chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person's health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration.

Handling Partially Observed Trial Data After Treatment Withdrawal: Introducing Retrieved Dropout Reference-Base Centred Multiple Imputation.

The ICH E9(R1) Addendum (International Council for Harmonization 2019) suggests treatment-policy as one of several strategies for addressing intercurrent events such as treatment withdrawal when defining an estimand. This strategy requires the monitoring of patients and collection of primary outcome data following termination of randomised treatment. However, when patients withdraw from a study early before completion this creates true missing data complicating the analysis.

Assessing efficacy in non-inferiority trials with non-adherence to interventions: Are intention-to-treat and per-protocol analyses fit for purpose?

Background: Non-inferiority trials comparing different active drugs are often subject to treatment non-adherence. Intention-to-treat (ITT) and per-protocol (PP) analyses have been advocated in such studies but are not guaranteed to be unbiased in the presence of differential non-adherence.

Methods: The REMoxTB trial evaluated two 4-month experimental regimens compared with a 6-month control regimen for newly diagnosed drug-susceptible TB.