Level Of Agreement Research Articles

Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management: Delphi consensus study

BACKGROUND Gastro-esophageal reflux disease (GERD) may affect the upper digestive tract; up to 20% of population in Western nations are affected by GERD. Antacids, histamine H2-receptor antagonists, and Proton Pump Inhibitors (PPIs) are considered the referring medications for GERD. Nevertheless, PPIs must be managed carefully because their use, especially chronic, could be linked with some adverse effects. An effective and safe alternative pharmacological tool for GERD is needed. After the identification of potentially new medications to flank PPIs, it is mandatory to revise and improve good clinical practices even through a consensus process. AIM To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method. METHODS The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel, subject of the consensus, is the basic prerequisite for the consensus itself. A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD. The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations: Gastroenterology, otolaryngology, geriatrics, and general medicine. A scientific committee analyzed the literature, determined areas that required investigation (in agreement with the multiple-choice questionnaire results), and identified two topics of interest: (1) GERD disease; and (2) GERD treatment. Statements for each of these topics were then formulated and validated. The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform. RESULTS According to their routinary GERD practice and current clinical evidence, the panel members provided feedback to each questionnaire statement. The experts evaluated 15 statements and reached consensus on all 15. The statements regarding the GERD disease showed high levels of agreement, with consensus ranging from 70% to 92%. The statements regarding the GERD treatment also showed very high levels of agreement, with consensus ranging from 90% to 100%. This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management, such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel. The consensus was unanimous among the physicians with different specializations, underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management. The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable (reducing PPIs administration to as-needed use), should be considered. CONCLUSION Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

An evaluation of 'ChatGPT' Compared to Dermatological Surgeons' Choice of Reconstruction of Mohs Surgical Defects.

ChatGPT® (OpenAI; California, USA) is an open-access chatbot developed using artificial intelligence (AI) that generates human-like responses. To evaluate the ChatGPT-4's concordance with three dermatologic surgeons on reconstructions for dermatological surgical defects. A total of 70 cases of non-melanoma skin cancer treated with surgery were obtained from clinical records for analysis. A list of 30 reconstruction options was designed by the main authors which included primary closure, secondary skin closure, skin flaps and skin grafts. Three blinded dermatologic surgeons, along with ChatGPT-4, were asked to select two reconstruction options from the list. Seventy responses were analyzed using Cohen's kappa looking for concordance between each dermatologist and ChatGPT. The level of agreement among dermatologic surgeons was higher compared to that between dermatologic surgeons and ChatGPT, highlighting differences in decision-making. In the best reconstruction technique, the results indicated a fair level of agreement among the dermatologists ranging between κ 0.268 and 0.331. However, the concordance with ChatGPT-4 and the dermatologists was slight with κ values from 0.107 to 0.121. In the analysis of the second-choice options, the dermatologists showed slight agreement. In contrast, the level of concordance between ChatGPT-4 and the dermatologists was below chance. As anticipated, this study reveals variability in medical decisions between dermatologic surgeons and ChatGPT. Although these tools offer exciting possibilities for the future, it's vital to acknowledge the risk of inadvertently rely on non-certified AI for medical advice.

Risk perception and use of personal care products by race and ethnicity among a diverse population

Personal care products can contain phthalates, parabens and other endocrine-disrupting chemicals. However, information on perception of risks from personal care product use and how use varies by race and ethnicity is limited. We evaluated differences in personal care product use and risk perception in a diverse sample of participants recruited from a US college campus and online. A self-administered questionnaire captured information on sociodemographic factors, personal care product use trends and perception of risk associated with them. Pearson’s chi-square and Fisher’s exact tests were used to determine differences in personal care product use and risk perception by race and ethnicity. Ordered logistic regressions were performed to measure associations between personal care product use frequency across racial/ethnic categories. Participant (n = 770) mean age was 22.8 years [standard deviation ± 6.0]. Daily use of make-up (eye = 29.3%; other = 38.0%; all = 33.7%) and skincare products (55%) was most frequently reported among Middle Eastern and North African participants. Non-Hispanic Black participants reported the highest daily use of hairstyling products (52%) and lotion (78%). Daily make-up use was more frequently reported among females (41%) than males (24.6%). Levels of agreement were similar across racial and ethnic groups, that personal care product manufacturers should be required to list all ingredients (≥87%). There were significant associations between the frequency of use of some personal care products and racial/ethnic categories when the use frequencies of participants from other racial/ethnic categories were compared to the use frequency of non-Hispanic White participants. There were significant differences in daily use frequency, levels of trust, perception of safety and health risks associated with personal care products by race and ethnicity, underscoring that there may be different sources of exposure to chemicals in personal care products by race and ethnicity.

Holding the hope? Therapist and client perspectives on long COVID recovery: A Q-methodology.

Long COVID is a global health concern which has debilitating effects on the individual experiencing it. In the United Kingdom, psychological therapies are being offered to people with long COVID, although the evidence for these therapies is yet to be demonstrated. This research aimed to understand how therapists and clients define and understand recovery from long COVID, and use hope theory to interpret the results. An online Q-methodology was employed, where participants sorted a range of statements pertaining to long COVID recovery based on their level of agreement with them. These arranged statements (Q-sorts) were collated and factor analysed to explore and compare underlying perspectives. Sixteen participants were recruited for the study, including eleven clients, four IAPT therapists and one therapist working in the broader long COVID pathway. A four-factor model is reported, including (1) Psychological Pathways to Recovery, (2) Social Context and Agency, (3) Physiological Goals of Recovery and (4) Personal Meaning Making. All IAPT therapists loaded onto the psychological pathways factor, whereas the remaining participants shared more diverse perspectives. The belief that long COVID recovery was possible, taken as an indicator of hopefulness, was rated highest for Factor 1, Psychological Pathways to Recovery, and Factor 3, Physiological Recovery Goals. This suggested that having a clear definition of recovery, or clear guidance on how to intervene, promoted hopefulness and, theoretically, well-being. However, clients reported experiences of being invalidated and disbelieved by health professionals, with psychological explanations sometimes being experienced as dismissive and invalidating. Clinical implications and future research directions are discussed.

Comparing the compensatory reserve metric obtained from invasive arterial measurements and photoplethysmographic volume-clamp during simulated hemorrhage.

The compensatory reserve metric (CRM) is a novel tool to predict cardiovascular decompensation during hemorrhage. The CRM is traditionally computed using waveforms obtained from photoplethysmographic volume-clamp (PPGVC), yet invasive arterial pressures may be uniquely available. We aimed to examine the level of agreement of CRM values computed from invasive arterial-derived waveforms and values computed from PPGVC-derived waveforms. Sixty-nine participants underwent graded lower body negative pressure to simulate hemorrhage. Waveform measurements from a brachial arterial catheter and PPGVC finger-cuff were collected. A PPGVC brachial waveform was reconstructed from the PPGVC finger waveform. Thereafter, CRM values were computed using a deep one-dimensional convolutional neural network for each of the following source waveforms; (1) invasive arterial, (2) PPGVC brachial, and (3) PPGVC finger. Bland-Altman analyses were used to determine the level of agreement between invasive arterial CRM values and PPGVC CRM values, with results presented as the Mean Bias [95% Limits of Agreement]. The mean bias between invasive arterial- and PPGVC brachial CRM values at rest, an applied pressure of -45mmHg, and at tolerance was 6% [-17%, 29%], 1% [-28%, 30%], and 0% [-25%, 25%], respectively. Additionally, the mean bias between invasive arterial- and PPGVC finger CRM values at rest, applied pressure of -45mmHg, and tolerance was 2% [-22%, 26%], 8% [-19%, 35%], and 5% [-15%, 25%], respectively. There is generally good agreement between CRM values obtained from invasive arterial waveforms and values obtained from PPGVC waveforms. Invasive arterial waveforms may serve as an alternative for computation of the CRM.

Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Comparison of two methods for collecting antimicrobial usage in large dairy farms in Ohio and California

Quantification of on-farm antimicrobial use (AMU) is critical to correlate with patterns of antimicrobial resistance, surveil­lance programs and formulate interventions to optimize its use. Prior studies have used the empty drug container (EDC) method to quantify AMU; however, the method is labor-intensive and time-consuming. Therefore, this study aimed to compare it against farm treatment records (FTR) as a reliable method to collect on-farm AMU. We hypothesized a low level of agreement in on-farm treatment incidence (TI) obtained between these 2 different collection methods.

Level of Agreement in Subjective Selection of Gingival Colour

Background and Objectives: Primary outcome: To assess the level of agreement between the objective and subjective methods for recording gingival colour in each area of the gingiva. Secondary outcome: To compare performance of the subjective visual method of gingival colour selection by a male observer and a female observer. Materials and Methods: A chromatic study was conducted on a total of 101 participants, in five gingival zones, from the free gingival margin to the mucogingival line, using a SpectroShade Micro spectrophotometer for the objective method and 21 ad hoc ceramic gingival shade tabs for the subjective method. A man and a woman of the same age, with the same amount of clinical experience in dentistry, selected the tab that most resembled the colour of participants’ gingiva. The “chromatic error” was then assessed by calculating the colour difference (using the Euclidean and CIEDE2000 formulae) between the CIELAB coordinates of the shade tab selected and the objective coordinates of the gingiva. The unweighted Kappa coefficient was used to calculate the level of agreement between observers. Results: For the male observer, the mean chromatic errors varied between ΔEab* 10.3 and 13.1 units, while for the female observer, the mean errors varied between ΔEab* 11.1 and 12.8: these differences were not statistically significant. Similarly, no statistically significant differences were found between the mean chromatic errors for the five gingival zones in either the male operator (p = 0.100) or the female operator (p = 0.093). The minimum level of agreement (unweighted Kappa) between the observers ranged from 0.1 to 0.4. Conclusions: Subjective selection of gingival colour was very inaccurate, by both the male observer and the female observer, for any area of the gingiva, with no differences identified between them. The level of agreement between the observers was low. These findings suggest that gingival colour should not be determined using solely subjective methods, given that the chromatic errors significantly exceeded the clinical acceptability threshold for gingiva (4.1 units for ΔEab* and 2.9 units for ΔE00). Both observers showed a tendency to select gingival shade tabs that were redder and bluer than the objective colours.

European Citizens’ Evaluation of the Common Agricultural Policy

The Common Agricultural Policy (CAP) is crucial in ensuring food safety and security in Europe. Providing a stable and diverse food supply also supports rural economies and promotes social, environmental and economic sustainability. However, as CAP consumes approximately 30% of the EU budget, debates regarding its pertinence have arisen. This paper aimed to understand European citizens’ perceptions of CAP, its associated benefits and their level of agreement regarding the allocation of the EU budget. Ultimately, the goal was to gain insights into EU citizens’ attitudes and perceptions towards the CAP. Information and data come from the European Survey Eurobarometer. The methods include statistical inferential techniques adjusted to the nature of the variables and goals. The findings confirm that European citizens generally perceive the CAP positively and have positive attitudes about the CAP. While some differences among various social groups may exist, the results did not identify any specific group strongly opposing the CAP. Overall, European citizens hold a favorable attitude towards the CAP, its associated benefits and budget allocation. This paper brings new insights into new European CAP measures and programs to promote food security and the sustainability of agriculture among European countries and citizens. These insights may be useful for public decision-makers to define better policies and measures adjusted to European citizens and to promote food security and sustainability.

Performance evaluation of loop-mediated isothermal amplification, polymerase chain reaction and real-time polymerase chain reaction methods to detect Neisseria gonorrhoeae among symptomatic patients from India.

Background: Neisseria gonorrhoeae is one of the most important causative organisms in causing sexually transmitted infections. The clinical presentation of gonorrhoea mimics the symptoms of other sexually transmitted infections, and a proper diagnosis of the same is therefore crucial in patient management. The current study intended to compare different in-house molecular methods: that is, conventional PCR, real-time PCR, and LAMP assay for detection of N. gonorrhoeae. Methods: A total of 163 samples were collected from 145 patients who presented with urethral and vaginal discharge. Collected samples were processed for culture on GC agar base, and three different molecular diagnostic tests (conventional PCR, real-time PCR, and LAMP assay) were performed simultaneously on all the samples. Results: Culture of N. gonorrhoeae was positive in 17 out of 21 (80.9%) swab samples. With culture as the gold standard method, conventional and real-time PCR had a sensitivity of 94.1%, whereas the sensitivity of the LAMP assay was found to be 88.2%. All three methods had a specificity of 100%. In addition to swab samples, evaluation of urine samples by different molecular methods yielded a good concordance with a kappa value of 0.85 by conventional PCR and real-time PCR showing a perfect level of agreement, while the LAMP assay was found to have a substantial level of agreement. Conclusion: LAMP assay had a comparable diagnostic accuracy to other molecular methods for the detection of N. gonorrhoeae and can be used as a point-of-care test in resource-limited settings.

Modeling carbonation depth of recycled aggregate concrete containing chlorinated salts

The durability of recycled concrete is susceptible to degradation from both chloride salt attack and carbonation when exposed in service environment. The depth of carbonation in recycled concrete subject to chloride salt attack was studied here. This investigation assessed the effects of mineral admixture, replacement rate of recycled coarse aggregate, and quality of recycled coarse aggregate on the carbonation depth. The carbonation depth Recycled concrete was studied through accelerated simulated carbonation in the laboratory for 7d, 14d and 28d. Based on the results, the correlation analysis was conducted to investigate the relationship between depth of carbonation, mineral admixture, recycled coarse aggregate replacement rate, recycled coarse aggregate quality and the presence of chloride ions. The objective of this study was mainly to investigate the effect of internal chloride ions on the depth of carbonation of recycled concrete subjected to chloride salt attack. The study referred to previous academic research on carbonation in recycled concrete that had not been affected by chloride salts, and conducted a comparative analysis to identify the carbonation depth pattern in recycled concrete influenced by chloride salt exposure. The study discovered a negative correlation between the replacement rate of mineral admixture and recycled coarse aggregate and the carbonation resistance of concrete. Moreover, enhancing the quality of recycled coarse aggregate positively impacted the carbonation resistance of concrete. An improved model was developed that considers the effect of internal chloride salts on the carbonation depth of recycled concrete, in reference to the empirical prediction model presently available. The model demonstrated a high level of agreement with experimental outcomes, displaying an error range of between −4.32% and 8.27%. It enables an in-depth comprehension of the carbonation behavior of recycled aggregate concrete in an environment exposed to chloride salt attack. Based on the model, the service life of recycled concrete structures can be more accurately forecasted, which can provide a theoretical direction for enhancing the durability of engineering structure.

Effectiveness of double cutout on lateral buckling analysis of fiber reinforced composites

AbstractLateral buckling, an essential mechanical phenomenon observed in composite beams subjected to specific external loads and boundary conditions, is influenced by various factors including cutout dimension, shape, position, and beam thickness in woven fabric laminated composite cantilever beams. The investigation focused on examining the lateral buckling behavior of beams containing two square or circular cutouts and comparing the experimental critical buckling loads of beams without any cutouts, which yielded results demonstrating a significant level of agreement. Through the experimental analysis, it was determined that square cutouts exhibit superior lateral buckling behavior when compared to circular cutouts.Highlights The effects of cutout shapes on lateral buckling analysis on fiber reinforced composites. The effects of cutout location on lateral buckling load on fiber reinforced composites. Comparison of the lateral buckling performances of fiber reinforced composites in relation to the type and position of cutouts.

Identifying core mental health services required for adult justice-involved populations in Australia: a Delphi study

This study aimed to define required forensic mental health service types in Australia. A staged Delphi process was used, including: (1) reference group consultation to establish a set of core forensic mental health service types; (2) Delphi survey to seek consensus on identified service types and definitions among forensic mental health stakeholders in Australia; and (3) amendment of service definitions in response to survey feedback. Nine forensic mental health service types were identified. Consensus (>80% agreement) was achieved among Delphi respondents that all services were core components of an ideal forensic mental health system. These included forensic bed-based (acute, sub-acute, non-acute, non-acute community), forensic community, outreach, prison and court liaison services. The high levels of agreement on service types are notable considering legislative differences impacting on design and operation of services across jurisdictions. The findings could contribute to the evidence base required for needs-based planning of forensic mental health services.

Comparative evaluation of the diagnostic accuracies of four different malaria rapid diagnostic test kits available in Ghana.

Malaria rapid diagnostic test (mRDT) kit is one of the techniques for diagnosing malaria. Due to its inherent advantages over the microscopy technique, several brands of the kit have flooded malaria endemic countries, without prior in-country evaluation. Two of such mRDT kits are Oscar (India) and Standard Q (Korea Republic). In this study, the performance of Oscar and Standard Q mRDT kits were compared to First Response (India) and CareStart (USA) mRDTs, which have been evaluated and deployed for use approved by the Ministry of Health (MOH). In this comparative study, whole blood samples were collected from patients suspected of malaria. Plasmodium falciparum was detected in each sample using nested polymerase chain reaction (nPCR), microscopy and the four mRDTs. The sensitivities, specificities, accuracies, positive and negative predictive values and accuracies of the mRDTs were determined using nPCR as a reference technique. Kappa statistic was used to determine the level of agreement among the techniques. Two hundred (200) blood samples were analyzed in this study. The overall detection rates of P. falciparum by microscopy, First Response, CareStart, Oscar-PfHRP2, Standard Q mRDT kits and nPCR were 31.5%, 34.5%, 33.5%, 32%, 31% and 43% (x2 = 6.1, p = 0.046), respectively. The accuracies of CareStart and First Response were comparable (90.5% vs. 89.5%). Further, comparing their sensitivities, Oscar-PfHRP2 was 74.4% (95% confidence interval (CI): 63.9-83.2) while that of Standard Q was 72.1% (95% CI: 61.4-81.2), with comparable accuracies (Oscar-PfHRP2-89% and Standard Q -88%). Apart from First Response that was 98.3% specific, the others were 100% specific. Kappa test revealed perfect diagnostic agreement (κ = 0.90-0.98) among the four mRDTs. That notwithstanding, Oscar-PfHRP2 agreed better with CareStart (κ = 0.94) and First Response (κ = 0.92) compared to the agreement between Standard Q and, CareStart (κ = 0.92) and First Response (κ = 0.90). Taken together, the diagnostic performance of the four mRDT kits were statistically similar. That notwithstanding, new mRDT kits should be evaluated prior to deployment for use.

A peridynamic-informed deep learning model for brittle damage prediction

Physics-informed Neural Network (PINN) has been introduced recently to predict and understand complex physical phenomena by directly incorporating feedback from governing equations. While PINNs offer remarkable capabilities, challenges arise when addressing discontinuities and heterogeneity, potentially compromising accuracy and reliability in prediction outcomes. In this study, a novel approach that combines the principles of peridynamic (PD) theory with PINN is presented to predict quasi-static damage and crack propagation in brittle materials. To achieve high prediction accuracy and convergence rate, the linearized PD governing equation is enforced in the PINN’s residual-based loss function. The proposed PD-INN is able to learn and capture complicated displacement patterns associated with different geometrical parameters, such as pre-crack position and length. The computational method presented in this study can be implemented to any PD constitutive model like Bond-Based PD or State-Based PD as well as any horizon factor. Several enhancements like cyclical annealing schedule and deformation gradient aware optimization technique are proposed to ensure the model would not get stuck in its trivial solution. The model’s performance assessment is conducted by monitoring the behavior of loss function throughout the training process. The results obtained through PD-INN demonstrate a satisfactory level of agreement in 2D and 3D when compared with the ground truth deformation from high-fidelity techniques like PD direct numerical method and Extended finite element method (X-FEM). Our results show the ability of the nonlocal PD-INN to predict damage and crack propagation accurately and efficiently.

Students' Perspective on Freedom of Expression and Hate Speech in Albanian Universities

This article presents an analysis of the perspective of university students in Albania toward freedom of expression and hate speech within the academic environment. This study confidently investigates Albanian university students’ attitudes and perceptions towards freedom of expression, its significance in academic institutions, and its relationship with principles of equality and non-discrimination. Based on survey data collected from 622 participants, the study examines student’s attitudes toward the freedom of expression and hate speech. Study results strongly support previous research that highlights the significance of freedom of expression for young people in high educational institutions. The high level of participant agreement on the importance of freedom of expression in this study provides further evidence of the universal recognition of this fundamental right. The study contributes valuable insights to the discourse on freedom of expression and its implications for fostering inclusive and respectful academic environments in Albania.   Received: 20 February 2024 / Accepted: 30 April 2024 / Published: 5 May 2024

Efficiency Assessment on Roof Geometry and Trombe Wall Shape for Improving Buildings’ Heating Performance

It is crucial to consider structural design issues in Trombe wall (T-wall) buildings to promote more suitable indoor climates and thermal comfort standards. Therefore, the present study examined the impact of two different T-wall designs and six different roof types on the energy and operational efficiency of a building located in a low-temperature and high-humidity winter climate. Ansys-CFX 15.0 software was employed to simulate the thermal and fluid dynamics behavior of the T-wall system, and flow, thermal comfort, energy, and exergy analyses were conducted. Three-dimensional simulation results and the pertinent literature data showed a good level of agreement, and the accuracy of the model was ensured. Outcomes revealed an average air velocity variation of 0.186 m/s and maximum average indoor air temperature variation of 3.3 °C between the six roof geometries. The highest air speed (0.988 m/s) was recorded for the gambrel roof while the lowest one (0.802 m/s) was recorded for the typical flat roof. The shed roof right with a rounded T-wall was more comfortable for standing and sitting activity than the others for the two T-wall shapes, and, at Y = 0.6 m and Y = 1.1 m, the average predicted percentages of dissatisfied (PPD) values were 31 and 28%, respectively. Furthermore, it was determined in the study that solar radiation intensity and T-wall and roof geometries had a significant effect on energy and exergy efficiency, and high energy and exergy efficiencies were achieved at higher solar intensity values. The best energy and exergy efficiencies were obtained for the butterfly and shed roof configurations. This study can serve as a reference for the thermal environment design of buildings with T-walls.

Schizophrenia spectrum disorders (SSD): an empirical benchmark study of real-world diagnostic accuracy and reliability among leading international psychiatrists

Abstract Background and hypothesis Assigning a psychiatric diagnosis in real-world situations is often difficult, given that the clinical presentation does not usually conform to the list of condensed, simplified behavioral descriptors of mainstream operational taxonomies (MOT) (e.g. ICD-11 and DSM-5). The goal of this study was to benchmark diagnostic accuracy and reliability on a central and severe spectrum of psychopathology (i.e., the schizophrenia spectrum disorders [SSD]), adopting a pragmatic approach as close as possible to real-world clinical settings. Study Design We examined the diagnostic performance of 30 international psychiatrists expert in SSD. The clinicians were asked to make their clinical best diagnostic estimate for two written clinical vignettes excerpted from real-world SSD cases. Study Results In the first vignette, 22 out of the 30 clinicians (73.5%) indicated a schizophrenia spectrum disorder as their main diagnostic hypothesis. In the second vignette, 12 clinicians (40%) chose SSD as their main diagnostic hypothesis. Only 10 of the 30 clinicians (33%) correctly identified both vignettes as cases of SSD. The level of inter-rater diagnostic agreement (Fleiss’ Kappa) was but statistically significant (KFleiss = 0.08, p = 0.01). Conclusions The results suggest that, even in a sample of influential international psychiatrists, the diagnostic accuracy and reliability on SSD presentations is poor and substantially inferior to those obtained in reliability studies using structured or semi-structured interviews. The widespread adoption of MOT systems in the last decades may have inadvertently eroded ability of clinicians to detect a typical pattern of psychiatric illnesses.

Abstract PO3-19-11: CINDERELLA Clinical Trial (NCT05196269): using artificial intelligence-driven healthcare to enhance breast cancer locoregional treatment decisions

Abstract Background. Breast cancer treatment has improved overall survival rates, with different locoregional approaches offering patients similar locoregional control but variable aesthetic outcomes that may lead to disappointment and poor quality of life (QoL). There are no standardized methods for informing patients of the different therapies prior to intervention, nor validated tools for evaluation of aesthetics and patients' expectations. The CINDERELLA Project is based on years of research and developments of new healthcare technologies by various partners, aimed to provide an artificial intelligence (AI) tool to aid shared decision-making by showing breast cancer patients the predicted aesthetic outcomes of their locoregional treatment. The clinical trial will evaluate the use of this tool within an AI cloud-based platform approach (CINDERELLA App) versus a standard approach. We anticipate that the CINDERELLA App will lead to improved satisfaction, psychosocial well-being and health-related QoL while maintaining the quality of care and providing environmental and economic benefits. Trial design. CINDERELLA is an international multicentric interventional randomized controlled open-label clinical trial. Using the CINDERELLA App, the AI and Digital Health arm will provide patients with complete information about the proposed types of locoregional treatments and photographs of similar patients previously treated with the same techniques. The Control arm will follow the standard approach of each clinical site. Randomization will be conducted online using the digital health platform CANKADO, ensuring a balanced distribution of participants between the two groups. CANKADO is the underlying platform through which physicians control the patients' app content and conduct all data collection. Privacy, data protection and ethical principles in AI usage were taken into account. Eligibility criteria. Patients diagnosed with primary breast cancer without evidence of systemic disease. All patients must sign an informed consent and be able to use a web-based app autonomously or with home-based support. Specific aims. Primary objective: to assess the levels of agreement among patients' expectations regarding the aesthetic outcome before and 12 months after locoregional treatment. The trial will also evaluate the aesthetic outcome level of agreement between the AI evaluation tool and self-evaluation. Secondary objectives: health-related QoL (EQ-5D-5L and BREAST-Q ICHOM questionnaires) and resource consumption (e.g., time spent in the hospital, out-of-pocket expenses). The questionnaires and photographs will be applied prior to any treatment, at wound healing, at 6 and 12 months following the completion of locoregional therapy. Statistical methods. Wilcoxon signed rank test will be used to assess the intervention's impact on the agreement level between expectations and obtained results. Weighted Cohen's kappa will be calculated to measure the improvement in classifying aesthetic results with intervention. Statistical tests and/or bootstrap techniques will compare results between arms. A similarity measure will be calculated between self-evaluation and outcome obtained with the AI tool for each participant, and a beta regression model will be used to analyze the intervention's effect. Secondary objectives will be evaluated by scoring questionnaires based on provided guidelines. Target accrual. The clinical trial, led by Champalimaud Clinical Centre, will enroll a minimum of 515 patients in each arm between July 2023 and January 2025. Recruitment is currently open at five study sites in Germany, Israel, Italy, Poland and Portugal. The clinical trial is still open for further international study sites. Funding. European Union grant HORIZON-HLTH-2021-DISEASE-04-04 Agreement No. 101057389. Citation Format: Eduard-Alexandru Bonci, Orit Kaidar-Person, Marília Antunes, Oriana Ciani, Helena Cruz, Rosa Di Micco, Oreste Davide Gentilini, Nicole Rotmensz, Pedro Gouveia, Jörg Heil, Pawel Kabata, Nuno Freitas, Tiago Gonçalves, Miguel Romariz, Helena Montenegro, Hélder P. Oliveira, Jaime S. Cardoso, Henrique Martins, Daniela Lopes, Marta Martinho, Ludovica Borsoi, Elisabetta Listorti, Carlos Mavioso, Martin Mika, André Pfob, Timo Schinköthe, Giovani Silva, Maria-Joao Cardoso. CINDERELLA Clinical Trial (NCT05196269): using artificial intelligence-driven healthcare to enhance breast cancer locoregional treatment decisions [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-11.

Abstract PO2-14-12: Accurate quantification of slide-level HER2 scores in breast cancer using a machine-learning model, AIM-HER2 Breast Cancer

Abstract Background: HER2 expression level is a key factor in determining the optimal treatment course for breast cancer patients. Roughly 15% of breast cancers are HER2(+), and determination of HER2 status is routinely assessed by immunohistochemistry (IHC). Accurate assessment of the HER2 IHC score (0, 1+, 2+, 3+) by pathologists is therefore critical, especially in light of novel therapeutic approaches demonstrating efficacy in the HER2-low setting (IHC scores 1+, and 2+/FISH-)1,2. To assist pathologists with the consistent provision of reproducible and accurate scores across the entire HER2 scoring range, we developed a machine-learning model (“AIM-HER2”) to generate accurate, slide-level HER2 scores aligned with ASCO-CAP guidelines in clinical breast cancer HER2 IHC specimens. Methods: AIM-HER2 was developed using whole-slide images (WSI; N=4261) from clinical and commercial sources. WSI were split into training (N=2694, 63%) and optimization (N=1567, 37%) sets. An additive multiple instance learning (aMIL) model3 was trained to predict HER2 scores directly from WSI and create interpretable heatmaps that depict HER2 predictions in tissue images. Image artifacts and in situ carcinomas were identified using previously trained artifact and tissue segmentation models and were excluded, leaving only regions of invasive carcinoma to be analyzed. AIM-HER2 performance was assessed on additional slides obtained from five academic or commercial sources (N=804 total, 770 evaluable) on which HER2 IHC was performed. Board-certified pathologists (N=52) with relevant experience provided manual HER2 scores based on ASCO-CAP guidelines. Nested pairwise non-inferiority analysis4 was used to compare model performance to that of pathologists (N=3 pathologists per slide). In the nested pairwise framework, agreement among pathologists was compared to agreement between AIM-HER2 and pathologists via linear kappa, so that summary metrics account for inter-pathologist variability. Results: High concordance was observed between AIM-HER2-predicted and pathologist-labeled slide-level HER2 scores, both overall and for each scoring level. Similar results were observed when assessing AIM-HER2 performance on multiple slide scanners and after IHC with multiple HER2 IHC antibody clones. Results are summarized in Table 1. Conclusions: We developed AIM-HER2, a novel aMIL-based approach for predicting slide-level HER2 IHC scores. AIM-HER2 has similar levels of agreement with pathologists as pathologists have with each other for determining HER2 score. This result is upheld when slides imaged using multiple scanning platforms and stained using multiple HER2 antibody clones. The performance of AIM-HER2 on multiple scanners and after multiple assays supports broad applicability of this algorithm in clinical laboratories, including for the identification of HER2-low cases. Work is ongoing to perform similar analyses in an independent, real-world dataset.