Development and validation of a biomarker index for HCC treatment response.

BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the LAD Score. An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927. CONCLUSIONS: Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring

Comparison of the Safety and Pharmacokinetics of ST-246® after IV Infusion or Oral Administration in Mice, Rabbits and Monkeys

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. plasma concentrations. These effects were eliminated using slower IV infusions. associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion

Evaluation of the Statistical Properties of Minimal Sufficient Balance as a Method for Controlling Baseline Covariate Imbalance for Sequential Clinical Trials with a Binary Endpoint

When there is a large number of baseline covariates whose imbalance needs to be controlled in sequential randomized controlled trials, minimization is most commonly used for randomizing treatment assignments. The lack of allocation randomness associated with the minimization method has been the source of controversy. The minimal sufficient balance (MSB) method is an alternative to minimization. It prevents serious imbalance from a large number of covariates while maintaining high levels of allocation randomness. However, a formal comparison between covariate-adaptive methods of randomization has not yet been studied. Using a re-randomization of the rt-PA clinical trial dataset with 1:1 equal allocation, minimization and MSB methods are compared with respect to allocation randomness, effectiveness at balancing covariates across treatment arms, and preservation of the nominal type I error rate. Using a simulated dataset, power and bias in the estimation of treatment effect are studied for completely randomized design, stratified permuted blocks, minimization, and MSB. A novel randomization method, known as allocation ratio preserving Minimal Sufficient Balance (ARP MSB) is presented as an alternative to allocation ratio preserving biased coin minimization (ARP BCM). Using a re-randomization of the rt-PA clinical trial dataset, ARP BCM and ARP MSB are compared with respect to the allocation randomness, effectiveness at balancing covariates across treatment arms, and preservation of the nominal type I error rate in unequal allocation clinical trials. MSB and ARP MSB methods proved to have equal or superior effectiveness at controlling imbalance on a combination of continuous and categorical variables, as well as a far greater proportion of completely random treatment assignments compared to the minimization and ARP BCM methods. MSB, ARP MSB, minimization, and ARP BCM all proved to have similar properties with respect to type I error rate preservation, power, and bias in measuring treatment effects. MSB and ARP MSB, while not presented as optimal methods for controlling covariate imbalances in sequential clinical trials, provide an alternative to the minimization and ARP BCM methods. The arguments in this dissertation should be considered by those who wish to use minimization or ARP BCM for subject allocation in clinical trials

Adaptive Experimentation in Digital Courseware using MOOClet

Using MOOClet, we demonstrate how we can add adaptivity to existing courseware that allows us to run real-time experiments that leverage multi-armed bandits. Ultimately, this allows us to provide students with the most successful interventions based on live data

Ixekizumab improves sleep and work productivity in patients with non-radiographic axial spondyloarthritis: results from the COAST-X trial at 52 weeks.

BACKGROUND: Patients with non-radiographic axial spondyloarthritis experience negative impacts on sleep, work productivity, and activity impairment. Ixekizumab, a monoclonal antibody selectively targeting interleukin-17A, has shown efficacy in treating the signs and symptoms of non-radiographic axial spondyloarthritis. This analysis evaluated the effect of ixekizumab treatment on sleep, work productivity, and activity impairment in patients with non-radiographic axial spondyloarthritis. METHODS: COAST-X ( NCT02757352 ) was a 52-week, phase 3, multicenter, randomised placebo-controlled trial evaluating 80-mg ixekizumab every 2 weeks and every 4 weeks in patients with active non-radiographic axial spondyloarthritis. Sleep disturbance was measured with the Jenkins Sleep Evaluation Questionnaire (JSEQ) and analysed using mixed-effects models for repeated measures. Work productivity and activity impairment were measured using the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis and analysed using analysis of covariance. Absenteeism, presenteeism, and overall work impairment were assessed for patients reporting paid work; activity impairment was assessed regardless of work status. RESULTS: Overall, patients treated with both dosing regimens of ixekizumab reported numerically greater improvements in sleep than placebo through Week 52. At Weeks 16 and 52, patients treated with ixekizumab every 4 weeks had significantly greater improvements in presenteeism (p = 0.007 and p = 0.003, respectively) and overall work impairment (p = 0.014 and p = 0.005, respectively) and numeric improvements in absenteeism than placebo. Patients treated with ixekizumab every 2 weeks had numerically greater improvements in absenteeism, presenteeism, and overall work impairment than placebo. Both dosing regimens of ixekizumab were associated with significantly greater improvements in activity impairment than placebo (ixekizumab every 4 weeks: p = 0.003 at Week 16 and p = 0.004 at Week 52; ixekizumab every 2 weeks: p = 0.007 at Week 16 and p = 0.006 at Week 52). CONCLUSIONS: Treatment with ixekizumab improved sleep, work productivity, and activity impairment in patients with nr-axSpA. Improvements in presenteeism and overall work impairment were sustained and consistent in the patients treated with ixekizumab every 4 weeks from Week 16 to Week 52. Improvements in activity impairment were sustained and consistent in both ixekizumab-treated groups from Week 16 to Week 52. TRIAL REGISTRATION: NCT02757352 , May 2, 2016

Utilization of health information technology among cancer genetic counselors

Abstract Background Health information technology (IT) is becoming increasingly utilized by cancer genetic counselors (CGCs). We sought to understand the current engagement, satisfaction, and opportunities to adopt new health IT tools among CGCs. Methods We conducted a mixed‐mode survey among 128 board‐certified CGCs using both closed‐ and open‐ended questions. We then evaluated the utilization and satisfaction among 10 types of health IT tools, including the following: cancer screening tool, family health history (FHx) collection tools, electronic health records (EHRs), telegenetics software, pedigree drawing software, genetic risk assessment tools, gene test panel ordering tools, electronic patient education tools, patient communication tools, and family communication tools. Results Seven of 10 health IT tools were used by a minority of CGCs. The vast majority of respondents reported using EHRs (95.2%) and genetic risk assessment tools (88.6%). Genetic test panel ordering software had the highest satisfaction rate (very satisfied and satisfied) at 80.0%, followed by genetic risk assessment tools (77.1%). EHRs had the highest dissatisfaction rate among CGCs at 18.3%. Dissatisfaction with a health IT tool was associated with desire to change: EHRs (p < .001), cancer screening tools (p = .010), genetic risk assessment tools (p = .024), and family history collection tools (p = .026). We found that nearly half of CGCs were considering adopting or changing their FHx tool (49.2%), cancer screening tool (44.9%), and pedigree drawing tool (41.8%). Conclusion Overall, CGCs reported high levels of satisfaction among commonly used health IT tools. Tools that enable the collection of FHx, cancer screening tools, and pedigree drawing software represent the greatest opportunities for research and development

Fitness attenuates long-term cardiovascular outcomes in women with ischemic heart disease and metabolic syndrome

Background: The prevalence of metabolic syndrome continues to increase steadily while fitness remains relatively low. The contribution of fitness on longer-term cardiovascular outcomes and mortality in individuals with cardiovascular disease and metabolic syndrome remains unknown. Design: Women's Ischemia Syndrome Evaluation (WISE) prospective cohort (enrolled 1996–2001) of women undergoing invasive coronary angiography with signs/symptoms of ischemic heart disease. Methods: Investigated the association of fitness, defined as >7METs measured by self-reported Duke Activity Status Index (DASI), and both metabolic syndrome (ATPIII criteria) and dysmetabolism (ATPIII criteria and/or treated diabetes) with long-term cardiovascular outcomes and all-cause mortality risk. Results: Among the 492 women followed for a median of 8.6 years (range 0–11 years), 19.5% were fit-metabolically healthy (reference), 14.4% fit-metabolic syndrome, 29.9% unfit-metabolically healthy, and 36.2% unfit-metabolic syndrome. Compared to reference, MACE risk was 1.52-fold higher in fit-metabolic syndrome women (HR 1.52, 95% CI 1.03–2.26) and 2.42-fold higher in unfit-metabolic syndrome women (HR 2.42, 95% CI 1.30–4.48). Compared to reference, mortality risk was 1.96-fold higher in fit-dysmetabolism (HR 1.96, 95% CI 1.29–3.00) and 3-fold higher in unfit-dysmetabolism women (HR 3.0, 95% CI 1.66–5.43). Conclusions: In a high risk cohort of women with signs/symptoms of ischemic heart disease, unfit-metabolically healthy and fit-metabolically unhealthy women were at higher risk of long-term MACE and mortality compared to fit-metabolically healthy women; and women who were unfit and metabolically unhealthy were at the highest risk. Our study demonstrates that metabolic health and fitness play an important role in long term outcomes that warrants further investigation. Registration: https://www.clinicaltrials.gov/ct2/show/NCT00000554 (NCT00000554

Abstract WP10: Impact of Prior Intravenous Thrombolysis on the Outcome of Emergent Carotid Stenting in Acute Stroke Patients With Tandem Occlusion: A Collaborative Pooled Analysis

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