US FDA Advisory Panel Members' Assessment of Premarket Approval Process and Suggestions for Improvement.

Importance: The manufacturing and marketing of medical devices is regulated by the US Food and Drug Administration (FDA), and the FDA premarket approval (PMA) process evaluates the safety and effectiveness of medical devices. The PMA process includes a detailed scientific, regulatory and quality system review and is critical to ensure that novel devices are safe, effective, and meet the needs of patients. Objective: To survey current voting members serving on panels of the FDA's Medical Devices Advisory Committee to better characterize panel decision-making and identify steps for improvement. Design, Setting, and Participants: This qualitative survey study included 36 questions that were mailed to FDA device panelists regarding their opinions on the influence of sources of information, pivotal trial design, quality of evidence, panel composition and internal deliberative process, time allocation, and impartiality of the FDA. The survey was mailed to the members of all 18 FDA device panels in January and February 2017. Data were collected from January to May 2017 and analyzed from 2018 to 2019. Exposures: Respondents read and returned the aforementioned paper survey, while nonrespondents did not. Main Outcomes and Measures: The main outcomes included panel members' perceptions, and their implications for process improvement. χ2 or Fisher exact tests were used to test differences between subgroups. Results: Of 64 of 92 panel members who responded (69.6%), 38 of 64 (59.4%) were male, 3 of 63 (4.8%) were Black respondents, 46 of 63 (73.0%) were White respondents, and 36 of 60 (60.0%) were in academic practice. The mean (range) panel service was 6.8 (1-22) years with 3.9 (1-19) meetings attended. Overall, respondents considered information presented by the FDA unbiased, and 28 of 61 (45.9%) believed that pivotal trials were frequently well-designed, 55 of 62 respondents (88.7%) suggested FDA consult panel members preemptively regarding trial design and 54 of 64 (84.4%) regarding the device label. Most indicated that prior FDA approval of another device serving the same medical purpose (43 of 62 [69.4%]) or approval in other countries with comparable regulatory regimes, such as Canada and Europe (39 of 62 [62.9%]), would make them more likely to recommend approval. Respondents rated written information (50 of 60 [83.3%]), live presentations (43 of 58 [74.1%]), and prior professional knowledge (41 of 60 [68.3%]) as the most important sources of information in deciding whether to recommend approval. Additionally, 52 of 58 respondents (89.7%) recommended that a panel member-only executive session would allow more clarity and honesty in deliberations, and 33 of 59 (55.9%) believed a three-fourths majority appropriate for recommending approval, which would be a deviation from the current system in which an overall vote is reported without designation of a vote threshold. Conclusions and Relevance: In this survey study of FDA device panel members, respondents wanted improved study designs, more relevant clinical data, including from other countries, involvement of panelists in study design and device label development, and inclusion of an executive session. Demographically, panels could be made more diverse.

Combining capillary electrophoresis and chemometric tools for the straightforward determination of imidazolinone herbicides in plant-based milks.

BACKGROUND: Highly polar herbicides, such as imidazolinones, are used for weed control to increase agricultural productivity and crop quality. However, their misapplication can lead to residues in ready-to-eat food with a potential health risk for consumers. Hence, the fast determination of these herbicides is necessary for timely action. In this work, an eco-friendly method based on capillary zone electrophoresis combined with chemometrics was used for the determination of imazapyr and imazamox in vegetable-based beverages such as soy and quinoa milk. RESULTS: The analytical strategy consisted of only three steps: (i) protein precipitation prior to sample injection (ii) data pre-processing to reduce the background and make corrections on electrophoretic times shift, and (iii) resolution of fully overlapped capillary electrophoresis (CE) peaks by the well-known partial least square (PLS) algorithm, which extracts quantitative information attributed to the analytes. The method was successfully applied in the concentration range between 1.00 and 100 µg L-1 with coefficient of determination of the calibration (R2 cal) and prediction (R2 pred) > 0.90, residual prediction deviation of calibration (RPDcal) and of prediction (RPDpred) > 3, and relative error of prediction (REP) > 11 in the analyzed sample matrices, in the three built methods (quinoa samples, soy samples, and joint quinoa and soy samples). CONCLUSION: The proposed methodology offers a simple and quick alternative for determining imidazolinones at trace concentrations in vegetable beverages, such as quinoa and soy milk, without complex sample preparation. The results were consistent with those obtained using more complex techniques, confirming the applicability of this method. © 2024 Society of Chemical Industry.

Evolving Paradigms in Prostate Cancer: The Integral Role of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Primary Staging and Therapeutic Decision-Making.

Prostate-specific membrane antigen (PSMA) positron emission tomography or computed tomography (PET/CT) has emerged as a superior imaging option to conventional imaging for prostate cancer. The majority of early evidence and prospective trials evaluated PSMA PET/CT in the biochemical recurrence or metastatic setting. However, there has been an increasing number of prospective trials in the primary setting. The purpose of this narrative review was to describe the role of PSMA PET/CT in localized primary prostate cancer. This narrative review focuses on the prospective evidence available in this setting. We detail the current practice and future potential for PSMA PET/CT to be used in multiple stages of localized primary prostate cancer. The most common practice currently for PSMA PET/CT is in the primary nodal and metastatic staging of high-risk prostate cancer. We describe other roles of PSMA PET/CT, including in intermediate-risk prostate cancer as well as local staging and the impact on radiation therapy and surgical management. We also discuss the potential future roles of PSMA PET/CT in prediagnosis such as risk stratification for biopsy, prognosis, and specific surgical roles. Potential pitfalls of PSMA PET/CT are also addressed. PSMA PET/CT has already had a significant influence on prostate cancer, and there will continue to be a greater role for this imaging modality in localized primary prostate cancer.

Cerebrospinal Fluid Homovanillic and 5-Hydroxyindoleacetic Acids in a Large Pediatric Population; Establishment of Reference Intervals and Impact of Disease and Medication.

BACKGROUND: Cerebrospinal fluid (CSF) homovanillic (HVA), and 5-hydroxyindoleacetic acids (5-HIAA) are biomarkers of neurological diseases affecting the dopaminergic and serotoninergic pathways. Establishing reference intervals for these metabolites faces the challenges of a lack of healthy controls and a negative correlation with age, making stratified intervals unrealistic. We propose a pipeline to determine continuous reference intervals for HVA and 5-HIAA using an indirect method. We also studied the confounding effects of different variables and explored the impact of antiepileptic and neuroleptic treatments on HVA and 5-HIAA values. METHODS: The study used least squares regression to fit age-concentration curves from a cohort of pediatric patients (n = 1533), where the residuals represent metabolite values excluding age effect. Presuming that HVA and 5-HIAA primary deficiencies characterize a distinct subpopulation, we fitted a two-component finite mixture model in age-normalized data and set reference intervals at the central 95% of the nondeficient population. RESULTS: Patients with primary genetic deficiencies of HVA and/or 5-HIAA consistently fall outside the proposed continuous reference intervals. Using the new continuous reference intervals reduces the number of secondary deficiencies detected compared with using stratified values. No correlations were observed between CSF HVA and 5-HIAA values across the studied drug categories (antiseizure and neuroleptic medications). In addition, biopterin values positively influenced both metabolite concentrations. CONCLUSION: The proposed continuous reference intervals caused a substantial reduction in the number of secondary deficiencies detected, most of which demonstrated no conclusive correlations between the diseases and altered HVA and 5-HIAA values.

The economic value of reducing avoidable mortality.

Living longer and healthier boosts individual and family welfare. As part of the World Bank's Healthy Longevity Initiative, we quantified the economic value of achieving the highest possible life span. We estimated the economic value of reducing avoidable mortality, defined as the difference between observed (or projected) mortality and lowest achieved (or projected) mortality, by world regions, sex, and age, between 2000 and 2021, with projection to 2050. In 2019, 69% of mortality, or 40 million deaths, was avoidable. The economic value of avoidable mortality globally was 23% of annual income, meaning that, globally, populations would be willing to give up about one-fifth of their current income in exchange for a year living at the lowest achieved mortality rate. This value ranges from 19% in China to 34% in sub-Saharan Africa. Under the rapid-progress scenario, in which countries experience fast but plausible mortality reductions from 2019 to 2050, we would expect globally the gap between projected and frontier life expectancy to be halved by 2050, and the economic value after achieving this scenario is equivalent to 14% of annual income. Our work provides supportive evidence on the high economic value placed on improving health.

The economic value of reducing mortality due to noncommunicable diseases and injuries.

With population aging, national health systems face difficult trade-offs in allocating resources. The World Bank launched the Healthy Longevity Initiative to generate evidence for investing in policies that can improve healthy longevity and human capital. As part of this initiative, we quantified the economic value of reducing avoidable mortality from major noncommunicable diseases and injuries. We estimated avoidable mortality-the difference between lowest-achieved mortality frontiers and projected mortality trajectories-for each cause of death, for 2000, 2019 and 2050, and for geographic regions, with high-income countries, India and China considered separately; we applied economic values to these estimates. The economic value of reducing cardiovascular disease avoidable mortality would be large for both sexes in all regions, reaching 2-8% of annual income in 2019. For cancers, it would be 5-6% of annual income in high-income countries and China, and for injuries, it would be around 5% in sub-Saharan Africa and Latin America and the Caribbean. Despite the large uncertainty surrounding our estimates, we offer economic values for reducing avoidable mortality by cause and metrics comparable to annual incomes, which enable multisectoral priority setting and are relevant for high-level policy discussions around budget and resource allocations.

Effect of concomitant medications on treatment response and survival in non-metastatic castrate resistant prostate cancer: Exploratory analysis of the SPARTAN trial.

BACKGROUND: We performed an exploratory analysis of the SPARTAN trial to determine whether concomitant exposure to several classes of commonly prescribed medications influenced the effect of apalutamide on overall survival (OS) and metastasis-free survival (MFS) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). PATIENTS AND METHODS: SPARTAN was a phase III randomized controlled trial in which nmCRPC patients were randomly assigned in a 2:1 ratio to receive androgen deprivation therapy with or without apalutamide. We focused on 5 commonly prescribed classes of medications: metformin, statins, angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), and proton pump inhibitors (PPI) based on a plausible biological and clinical rationale. To determine the potential effect modification, we applied multivariable Cox regression models for OS and MFS separately with additional interaction terms. To determine the independent association of concomitant medications with OS and MFS, we used IPTW-based log-rank test. A 2-sided p < 0.01 was considered statistically significant. RESULTS: We did not find statistically significant differences in effect from apalutamide on OS across subgroups stratified by concomitant exposure to any of the medication classes. While there was some difference in the treatment effect from apalutamide on MFS between patients with concomitant statins (adjusted hazard ratio [aHR]: 0.20; 95 % CI: 0.15-0.28) versus without concomitant statins (aHR: 0.31 [0.24-0.39]), this did not reach the pre-specified threshold of statistical significance (p = 0.011). On IPTW-based analysis, patients treated concomitantly with metformin (median: not reached versus 31 months; p = 0.002), or ACEI (median: 37 versus 29 months, p = 0.006) had significantly improved MFS. CONCLUSIONS: In this post-hoc exploratory analysis of SPARTAN, effects of apalutamide on MFS and OS were consistent across subgroups stratified by exposure to concomitant medications. Exposure to concomitant metformin and ACEI was independently associated with a significant improvement in MFS.

Sense of coherence in stroke: A concept analysis with Rodger's evolutionary approach.

Sense of coherence (SoC) refers to how individuals cope with stress and maintain health, yet its concept remains no consensus about how it is defined and applied in the context of stroke care. This study aims to clarify the concept of SoC by reviewing its applications in various stroke populations and its changes across different stages of stroke. The adapted steps of Rodger's evolutionary approach of concept analysis were used to explore the attributes, surrogate or related terms, antecedents, and consequences of SoC in stroke. Twenty-five articles were included after evaluating 1065 records and 80 full-text articles. The SoC's attributes, characterized with dynamicity of comprehensibility, manageability, and meaningfulness in stroke, lie within the different stroke phases (acute, sub-acute and chronic). There is no surrogate term to SoC. Related terms included coping, resistance resources, resilience, hardiness, and readiness. Antecedents related to stroke survivors and informal caregivers included sociodemographic factors, body functioning factors, social factors, stroke-related factors, and caring factors. Consequences for stroke survivors, informal caregivers, and dyads included psychological status, health behavior, marital satisfaction, care provision, and perception of rehabilitation needs. The findings of the concept analysis of SoC in stroke reveal that this concept extends beyond survivors experienced stroke, and its comprehensive understanding needs considering various aspects including the SoC of informal caregivers, dyads, and family. This paper serves as a novel perspective for future stroke care, focusing on the needs for dynamic monitoring and adaptations to changes of SoC at different stages of stroke care. A proper understanding of SoC can also contribute to developing assessment tools and theoretical models in stroke care with some emphasis on the phases of strokes (attributes), demographic and functional characteristics (antecedents), and both stroke survivor-caregiver-related outcomes sensitive to SoC.

Maternal depression and early childhood development among children aged 24-59 months: the mediating effect of responsive caregiving.

This study examined whether maternal depression is related to Early Childhood Developmental (ECD) delay among children by quantifying the mediating contribution of responsive caregiving. We used data from 1235 children (Children's mean age = 50.4 months; 582 girls, 653 boys, 93.9% were Han), selected through convenience sampling, in 2021. 4.7% of children had ECD delay, 34.3% of mothers had depression. Children with depressed mothers were less likely to receive responsive caregiving (OR 4.35, 95% CI 2.60-7.27), and those who did not receive responsive caregiving were more likely to experience ECD delay (OR 3.89, 95% CI 1.89-8.02). Responsive caregiving partly mediated the relationship between maternal depression and ECD. Early intervention for children with depressed mothers is worthy of further investigation.

Utility of artificial intelligence in the diagnosis and management of keratoconus: a systematic review.

Introduction: The application of artificial intelligence (AI) systems in ophthalmology is rapidly expanding. Early detection and management of keratoconus is important for preventing disease progression and the need for corneal transplant. We review studies regarding the utility of AI in the diagnosis and management of keratoconus and other corneal ectasias. Methods: We conducted a systematic search for relevant original, English-language research studies in the PubMed, Web of Science, Embase, and Cochrane databases from inception to October 31, 2023, using a combination of the following keywords: artificial intelligence, deep learning, machine learning, keratoconus, and corneal ectasia. Case reports, literature reviews, conference proceedings, and editorials were excluded. We extracted the following data from each eligible study: type of AI, input used for training, output, ground truth or reference, dataset size, availability of algorithm/model, availability of dataset, and major study findings. Results: Ninety-three original research studies were included in this review, with the date of publication ranging from 1994 to 2023. The majority of studies were regarding the use of AI in detecting keratoconus or subclinical keratoconus (n=61). Among studies regarding keratoconus diagnosis, the most common inputs were corneal topography, Scheimpflug-based corneal tomography, and anterior segment-optical coherence tomography. This review also summarized 16 original research studies regarding AI-based assessment of severity and clinical features, 7 studies regarding the prediction of disease progression, and 6 studies regarding the characterization of treatment response. There were only three studies regarding the use of AI in identifying susceptibility genes involved in the etiology and pathogenesis of keratoconus. Discussion: Algorithms trained on Scheimpflug-based tomography seem promising tools for the early diagnosis of keratoconus that can be particularly applied in low-resource communities. Future studies could investigate the application of AI models trained on multimodal patient information for staging keratoconus severity and tracking disease progression.

Vernal keratoconjunctivitis in adults: a narrative review of prevalence, pathogenesis, and management.

Vernal keratoconjunctivitis (VKC) is a chronic, progressive, allergic ocular surface disorder that can lead to sight-threatening complications. VKC occurs primarily in children and generally resolves about the time of puberty; however, case series and retrospective analyses indicate that approximately 10% of patients with VKC are adults, and that a subset of adult cases develop after puberty. Consequently, two age-related variants of VKC have recently been described: early-onset VKC-which manifests during childhood and persists into adult life-and late-onset disease, which emerges de novo after puberty. Although the signs and symptoms of adult and childhood VKC are similar, adult VKC is a long-lasting disease characterized by severe inflammation and increased risk of conjunctival fibrosis, which may place adult patients at higher risk for sight-threatening complications and adverse impacts on daily life. This review discusses the epidemiology, signs, symptoms, immunopathogenesis of adult VKC variants, and highlights current gaps in research and management of patients with this condition.

Disparities in glaucoma and macular degeneration healthcare utilization among persons living with dementia in the United States.

PURPOSE: Dementia is common among patients with primary open angle glaucoma (POAG) and neovascular age-related macular degeneration (nAMD). This study compares visit frequency, diagnostic test utilization, and treatment patterns for POAG and nAMD among persons with vs. without dementia. METHODS: Optum's de-identified Clinformatics® Data Mart Database (January 1, 2000-June 30, 2022) was used for this study. Two cohorts were created from newly diagnosed POAG or nAMD patients. Within each cohort, an exposure cohort was created of newly diagnosed dementia patients. The primary outcome was the number of visits to an eye care provider. Secondary analyses for the POAG cohort assessed the number of visual field tests, optical coherence tomography (OCT), and glaucoma medication prescription coverage. The secondary analysis for the nAMD cohort included the number of injections performed. Poisson regression was used to determine the relative rates of outcomes. RESULTS: POAG patients with dementia had reduced rates of eye care visits (RR 0.76, 95% CI: 0.75-0.77), lower rates of testing utilization for visual fields (RR 0.66, 95% CI: 0.63-0.68) and OCT (RR 0.67, 95% CI: 0.64-0.69), and a lower rate of glaucoma prescription medication coverage (RR 0.83, 95% CI: 0.83-0.83). nAMD patients with dementia had reduced rates of eye care visits (RR 0.74, 95% CI: 0.70-0.79) and received fewer intravitreal injections (RR 0.64, 95% CI: 0.58-0.69) than those without dementia. CONCLUSIONS: POAG and nAMD patients with dementia obtained less eye care and less monitoring and treatment of their disease. These findings suggest that this population may be vulnerable to gaps in ophthalmic care.

Epidemiology of patch tested patients with permanent tattoos-A comparative analysis of 9693 IVDK patients (2020-2022).

BACKGROUND: Permanent tattooing is the invasive introduction of tattoo ink (pigments) into the dermis. The ink and aftercare cosmetics applied on pre-damaged skin may contain skin sensitisers. OBJECTIVES: To identify patient characteristics and the pattern of sensitisation in tattooed patients patch tested within the Information Network of Departments of Dermatology (IVDK). PATIENTS AND METHODS: Comparative analysis of patient characteristics and reaction frequencies to baseline series allergens in 1648 consecutive patients with and 8045 consecutive patients without permanent tattoos. Non-overlapping 95%-confidence intervals were considered as significant. RESULTS: Having permanent tattoos was related with female sex, age <40 years, tobacco smoking, atopic dermatitis, (occupational) hand dermatitis and being employed in particular occupational groups (e.g., healthcare workers, mechanics, hairdressers). Sensitisation to nickel was increased in tattooed patients and associated with female sex (OR 4.23 [95%-CI, 3.48-5.18]), age ≥40 years (OR 1.26 [95%-CI, 1.08-1.49]), tobacco smoking (OR 1.19 [95%-CI, 1.01-1.40]) and having permanent tattoos (OR 1.27 [95%-CI, 1.05-1.53]). CONCLUSIONS: The association between nickel sensitisation and permanent tattoos is probably confounded by past reactions to pierced costume jewellery. Socio-economic factors most probably contribute to the connection between tattoos, tobacco smoking, occupational or hand dermatitis, and being employed in particular occupational groups.

Use of Decipher Prostate Biopsy Test in Patients with Favorable-risk Disease Undergoing Conservative Management or Radical Prostatectomy in the Surveillance, Epidemiology, and End Results Registry.

BACKGROUND AND OBJECTIVE: The extent of prostate cancer found on biopsy, as well as prostate cancer grade and genomic tests, can affect clinical decision-making. The impact of these factors on the initial management approach and subsequent patient outcomes for men with favorable-grade prostate cancer has not yet been determined on a population level. Our objective was to explore the association of Decipher 22-gene genomic classifier (GC) biopsy testing on the initial use of conservative management versus radical prostatectomy (RP) and to determine the independent effect of GC scores on RP pathologic outcomes. METHODS: A total of 87 140 patients diagnosed with grade group 1 and 2 prostate cancer between 2016 and 2018 from the Surveillance, Epidemiology, and End Results registry data were linked to GC testing results (2576 tested and 84 564 untested with a GC). The primary endpoints of interest were receipt of conservative management or RP, pathologic upgrading (pathologic grade group 3-5), upstaging (pathologic ≥T3b), and adverse pathologic features (pathologic upgrading, upstaging, or lymph node invasion). Multivariable logistic regressions quantified the association of variables with outcomes of interest. KEY FINDINGS AND LIMITATIONS: GC tested patients were more likely to have grade group 2 on biopsy (51% vs 46%, p < 0.001) and lower prostate-specific antigen (6.1 vs 6.3, p = 0.016). Conservative management increased from 37% to 39% and from 22% to 24% during 2016-2018 for the GC tested and untested populations, respectively. GC testing was significantly associated with increased odds of conservative management (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.9-2.4, p < 0.001). The distribution of biopsy GC risk was as follows: 45% low risk, 30% intermediate risk, and 25% high risk. In adjusted analyses, higher GC (per 0.1 increment) scores (OR 1.24, 95% CI 1.17-1.31, p < 0.001) and percent positive cores (1.07, 95% CI 1.02-1.12, p = 0.009) were significantly associated with the receipt of RP. A higher GC score was significantly associated with all adverse outcomes (pathologic upgrading [OR 1.29, 95% CI 1.12-1.49, p < 0.001], upstaging [OR 1.31, 95% CI 1.05-1.62, p = 0.020], and adverse pathology [OR 1.27, 95% CI 1.12-1.45, p < 0.001]). Limitations include observational biases associated with the retrospective study design. CONCLUSIONS AND CLINICAL IMPLICATIONS: Men who underwent GC testing were more likely to undergo conservative management. GC testing at biopsy is prognostic of adverse pathologic outcomes in a large population-based registry. PATIENT SUMMARY: In this population analysis of men with favorable-risk prostate cancer, those who underwent genomic testing at biopsy were more likely to undergo conservative management. Of men who initially underwent radical prostatectomy, higher genomic risk but not tumor volume was associated with adverse pathologic outcomes. The use of genomic testing at prostate biopsy improves risk stratification and may better inform treatment decisions than the use of tumor volume alone.

Clinical and economic evaluation of tralokinumab for atopic dermatitis.

Tralokinumab is the first selective interleukin 13 inhibitor approved for moderate to severe atopic dermatitis. This article reports the findings of a comprehensive literature review and extensive economic analysis to assess tralokinumab's safety, effectiveness, and cost. Evidence synthesis involved evaluating comparative effectiveness and conducting economic sensitivity analyses. This review was prepared by the University of Connecticut School of Pharmacy Academy of Managed Care Pharmacy (AMCP) Student Chapter. The student author group won the AMCP National Pharmacy and Therapeutics competition for their tralokinumab product review in March 2023.

Early Prostate-Specific Antigen Response by 6 Months Is Predictive of Treatment Effect in Metastatic Hormone Sensitive Prostate Cancer: An Exploratory Analysis of the TITAN Trial.

PURPOSE: Early PSA response has been found to be prognostic of outcomes in metastatic hormone sensitive prostate cancer. We performed a secondary analysis of the TITAN trial to determine if early PSA response was predictive of treatment efficacy in metastatic hormone sensitive prostate cancer patients. MATERIALS AND METHODS: Early PSA response was defined as achieving a PSA level of ≤ 0.2 ng/mL by 6 months of random assignment. A Cox proportional hazard model was constructed in a landmark population with an interaction term between the treatment and early PSA response to determine differential treatment effect on overall survival (OS). We applied multivariable Cox proportional hazard regression model with time to early PSA response fitted with restricted cubic spline to determine the association of time to early PSA response with OS. RESULTS: Approximately 24% (124/524) of patients in the androgen deprivation therapy (ADT) alone group and 61% (321/524) in the apalutamide group had PSA response ≤ 0.2 ng/mL by 6 months. Longer time to early PSA response was associated with significantly superior OS in the apalutamide group. There was a significant difference in treatment effect from apalutamide on OS (P = .03 for interaction) among 6-month PSA responders (HR: 0.66; 95% CI: 0.44-1.00) vs nonresponders (HR: 1.14; 95% CI: 0.89-1.46). This difference in treatment effect was not statistically significant at 3 months (P = .17 for interaction). Among 6-month PSA responders, 3-year confounder-adjusted OS was 84% (80%-88%) for the apalutamide group and 74% (66%-82%) for the ADT alone group. Among nonresponders, 3-year adjusted OS for the 2 treatment arms were 58% (52%-65%) and 56% (51%-60%), respectively. CONCLUSIONS: Early PSA response by 6 months was a predictor of treatment efficacy from ADT plus apalutamide on OS. Longer time to early PSA response was associated with superior OS in the apalutamide arm.

The Next Generation: Surgeon Learning Curve in a Mature Operative Rib Management Program.

INTRODUCTION: Prior work has demonstrated utility in using operative time to measure surgeon learning for surgical stabilization of rib fractures (SSRF); however, no studies have used operative time to evaluate the benefit of proctoring in subsequent generations of surgeons. We sought to evaluate whether there is a difference in learning between an original series (TOS) of self-taught surgeons versus the next generation (TNG) of proctored surgeons using cumulative summation (CUSUM) analysis. We hypothesized that TNG would have a comparatively accelerated learning curve. METHODS: A single-center retrospective review of all SSRF at a level 1 trauma center was performed. Data were collected from the beginning of an operative chest injury program to include at least 2 y of TNG experience. Operative time was used to determine success and misstep based on prior methods. Learning curves using CUSUM analysis were calculated based on an anticipated success rate of 90% and compared between TOS and TNG groups. RESULTS: Over 7 y, 163 patients with a median Injury Severity Score of 24 underwent SSRF. Median operative time was 165 min with a 0.5 plate-to-fracture ratio. All three TOS surgeons experienced a positive slope indicative of early missteps for their first 15-20 cases. By contrast, all three TNG surgeons demonstrated a series of early successes resulting in negative CUSUM slopes which coincided with a period of proctoring. By the end of TNG series, the composite cumulative score was less than half of the TOS surgeon' scores. CONCLUSIONS: Operative time continues to be a useful surrogate for observing SSRF learning curves. In a mature institutional program, proctored novice surgeons appear to have an accelerated learning curve compared to novice surgeons developing a new operative rib program.

A Theory and Evidence-Based Artificial Intelligence-Driven Motivational Digital Assistant to Decrease Vaccine Hesitancy: Intervention Development and Validation.

Vaccine hesitancy is one of the top ten threats to global health. Artificial intelligence-driven chatbots and motivational interviewing skills show promise in addressing vaccine hesitancy. This study aimed to develop and validate an artificial intelligence-driven motivational digital assistant in decreasing COVID-19 vaccine hesitancy among Hong Kong adults. The intervention development and validation were guided by the Medical Research Council's framework with four major steps: logic model development based on theory and qualitative interviews (n = 15), digital assistant development, expert evaluation (n = 5), and a pilot test (n = 12). The Vaccine Hesitancy Matrix model and qualitative findings guided the development of the intervention logic model and content with five web-based modules. An artificial intelligence-driven chatbot tailored to each module was embedded in the website to motivate vaccination intention using motivational interviewing skills. The content validity index from expert evaluation was 0.85. The pilot test showed significant improvements in vaccine-related health literacy (p = 0.021) and vaccine confidence (p = 0.027). This digital assistant is effective in improving COVID-19 vaccine literacy and confidence through valid educational content and motivational conversations. The intervention is ready for testing in a randomized controlled trial and has high potential to be a useful toolkit for addressing ambivalence and facilitating informed decision making regarding vaccination.