Optimal Definition Research Articles

Diagnostic Accuracy Performance of Fluorescence In Situ Hybridization (FISH) for Biliary Strictures: A Systematic Review and Meta-Analysis

Background and Aims: This systematic review and meta-analysis aims to compare the performance of UroVysion® FISH based on the different definitions of a positive result used in published literature with the goal of determining the optimal FISH definition for detecting pancreaticobiliary malignancy. Methods: A systematic literature search identified studies from database inception to Sept 2024 that evaluated the diagnostic performance of FISH in determining malignancy among patients with biliary strictures. All thresholds for positive FISH, as defined by the individual study, were included in this review. Subgroup analysis was performed based on the definitions of positive FISH as follows: (1) polysomy only; (2) polysomy, tetrasomy, or trisomy; and (3) polysomy or 9p deletion. Results: Eighteen studies comprising 2516 FISH specimens were analyzed, including 1133 (45.0%) with malignancy. Using a threshold for positivity as defined in individual studies, the overall sensitivity of FISH was 57.6% (95% confidence interval [CI], 49.4–65.4%), and the overall specificity was 87.8% (95% CI, 79.2–93.2%). Subgroup analysis showed that polysomy as the threshold for positive FISH yielded a sensitivity of 49.4% (95% CI, 43.2–55.5%), with an increased specificity of 96.2% (95% CI, 92.7–98.1%), while polysomy + tetrasomy/trisomy as positive FISH resulted in an increased sensitivity of 64.3% (95% CI 55.4–72.2%) but a decreased specificity of 78.9% (95% CI 64.4–88.5%). The addition of 9p deletion to polysomy as the criteria for a positive test resulted in a non-significant increase in sensitivity (54.7% (95% CI 42.4–66.5%) while maintaining specificity (95.1% (95% CI 84.0–98.6%). Conclusions: Based on these findings, polysomy only or polysomy/9p deletion should be considered as the criterion for defining a positive FISH test to improve diagnostic sensitivity while maintaining high specificity.

Heatwave and upper urinary tract stones morbidity: effect modification by heatwave definitions, disease subtypes, and vulnerable populations.

As heatwave occurs with increased frequency and intensity, the disease burden for urolithiasis, a heat-specific disease, will increase. However, heatwave effect on urolithiasis subtypes morbidity and optimal heatwave definition for urolithiasis remain unclear. Distributed lagged linear models were used to assess the associations between 32 defined heatwave and upper urinary tract stones morbidity. Relative risk (RR) and attributable fraction (AF) of upper urinary tract stone morbidity associated with heatwave of different intensities (low, middle, and high) were pooled by meta-analysis. Optimal heatwave definition was selected based on the combined score of AF, RR, and quasi-Akaike Information Criterion (QAIC) value. Stratified analyses were conducted to investigate the modification effects of gender, age, and disease subtypes. Association between heatwave and upper urinary tract stones morbidity was mainly for ureteral calculus, and AF was highest for low-intensity heatwave. This study's optimal heatwave was defined as average temperature > 93rd percentile for ≥ 2 consecutive days, with AF of 7.40% (95% CI:2.02%, 11.27%). Heatwave was associated with ureteral calculus morbidity in males and middle-aged adults. While heatwave effect was statistically insignificant in females and other age groups. Managers should develop appropriate definitions to address heatwave based on regional characteristics and focus on heatwave effects on urolithiasis.

Automated Neural Architecture Search for Cardiac Amyloidosis Classification from [18F]-Florbetaben PET Images.

Medical image classification using convolutional neural networks (CNNs) is promising but often requires extensive manual tuning for optimal model definition. Neural architecture search (NAS) automates this process, reducing human intervention significantly. This study applies NAS to [18F]-Florbetaben PET cardiac images for classifying cardiac amyloidosis (CA) sub-types (amyloid light chain (AL) and transthyretin amyloid (ATTR)) and controls. Following data preprocessing and augmentation, an evolutionary cell-based NAS approach with a fixed network macro-structure is employed, automatically deriving cells' micro-structure. The algorithm is executed five times, evaluating 100 mutating architectures per run on an augmented dataset of 4048 images (originally 597), totaling 5000 architectures evaluated. The best network (NAS-Net) achieves 76.95% overall accuracy. K-fold analysis yields mean ± SD percentages of sensitivity, specificity, and accuracy on the test dataset: AL subjects (98.7 ± 2.9, 99.3 ± 1.1, 99.7 ± 0.7), ATTR-CA subjects (93.3 ± 7.8, 78.0 ± 2.9, 70.9 ± 3.7), and controls (35.8 ± 14.6, 77.1 ± 2.0, 96.7 ± 4.4). NAS-derived network performance rivals manually determined networks in the literature while using fewer parameters, validating its automatic approach's efficacy.

BIG DATA, BUSINESS PROCESSES, AND MATHEMATICAL ALGORITHMS FOR MULTI-OBJECTIVE MANAGERIAL DECISION OPTIMIZATION

The use of Big Data and the engineering of business processes are becoming increasingly important for managing the business of companies and large international corporate groups. For more successful outcomes, even for complex interventions such as those of the PNRR (National Recovery and Resilience Plan), the use of mathematical models to assist management decisions represents a significant lever to optimize time, costs, and planned overall performance. This analytical approach strengthens traditional qualitative techniques like SWOT analysis and finds useful application in the optimal definition of any form of PPP (Public-Private Partnership), such as the recent “Partnership for Innovation” (PPI) included in the new procurement code. The scientific work developed from the systematic analysis of processes proposes a particular multi-objective mathematical model that uses a system of vectors in an m-dimensional reference space.

Identifying homelessness using health administrative data in Ontario, Canada: how coding policies impact case validity

Conducting longitudinal research about the health of people experiencing homelessness poses unique challenges. In Canada, we previously demonstrated that identification through health administrative databases permits population-level studies, despite relatively low sensitivity. Since then, coding of homelessness became mandatory in hospitals nationally. As a result, case validity since 2018 is unknown. We re-validated case definitions for identifying homelessness in health administrative databases between 2018 and 2022 against the longitudinally collected housing history of a representative sample of people experiencing homelessness (n=640) and randomly selected, housed people (n=128,000) in Toronto, Canada. We calculated sensitivity, specificity, positive and negative predictive values, and positive likelihood ratios for 42 unique case definitions. We compared the resulting true positives against false positives and false negatives to identify potential causes of misclassification. The optimal case (best sensitivity/scalability beyond Ontario) definition included any indicator during a hospital-based encounter within 180 days of a period of homelessness (sensitivity=52.9%; specificity=99.5%). Among periods of homelessness with ≥1 hospital-based encounter, the optimal case definition had good sensitivity (75.1%) with minimal reduction in specificity (98.5%). Review of false positives suggests homeless status is sometimes improperly carried forward in healthcare encounters occurring after transitioning out of homelessness. Case definitions to identify homelessness using health administrative data exhibit moderate sensitivity and excellent specificity, with two-fold increases in sensitivity since the implementation of mandatory coding in Canada. Mandatory collection of social determinants of health information within administrative data present invaluable opportunities for advancing research on the health and healthcare needs of people experiencing homelessness.

Comparison of the prevalence and associated factors of chronic kidney disease diagnosed by serum creatinine or cystatin C among young people living with HIV in Uganda.

Young people living with HIV (YPLHIV) are at increased risk of developing chronic kidney disease (CKD) which is associated with high mortality and morbidity. Early diagnosis is important to halt progression. We aimed to estimate the prevalence and factors associated with CKD among YPLHIV in Kampala, Uganda, and to compare serum creatinine and cystatin C for early diagnosis of CKD in this population. A cross-sectional study with YPLHIV aged 10 to 24 years was conducted in seven HIV clinics. Participants provided a urine and blood sample to measure urinary albumin, proteinuria, serum creatinine and cystatin C levels at baseline and after three months. The estimated glomerular filtration rate (eGFR) was calculated using CKDEPI 2021, Cockroft-Gault and bedside Schwartz equations using creatinine or cystatin C. The albumin creatinine ratio (ACR) and proteinuria were measured. CKD was defined as either eGFR <60ml/min/1.73m2 or <90ml/min/1.73m2 or ACR above 30mg/g on two separate occasions. Univariable and multivariable logistic regression were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with CKD. A total of 500 participants were enrolled. Most were female (56%; n=280) and aged 10 to 17 years (66.9%; n=335). CKD prevalence ranged from 0-23% depending on the criteria, equation and biomarker used. Cystatin C-based equations estimated higher prevalence of CKD compared to creatinine-based ones. Prevalence of ACR above 30mg/g was 10.1% and of proteinuria 29%. Factors independently associated with CKD were age (aOR=1.42; 95% CI:1.30-1.51) and male sex (aOR=3.02; 95% CI:1.68-5.43). CKD prevalence among YPLHIV varied substantially depending on definitions used and the current definition would likely lead to missed cases of CKD among YPLHIV. Estimating equations should be validated against measured GFR in YPLHIV and the optimal definition of CKD in this vulnerable population should be revised to optimise detection and opportunities for reducing disease progression.

Research on the Practical Teaching Model of E-commerce in Higher Vocational Education Based on OBE Principles—A Case Study of CK Vocational College

To fundamentally enhance the internal construction of higher vocational colleges and improve the quality of talent cultivation has become an urgent issue to address. The key to enhancing the quality of talent cultivation lies in, based on a thorough consideration of the characteristics of higher vocational students, starting from the talent cultivation system, and focusing on the construction and reform of courses, teaching, and faculty. The OBE educational philosophy emphasizes a results-oriented approach to talent cultivation, centering on the student, stimulating learning enthusiasm, and promoting the internalization of students' knowledge, abilities, and values into their learning and career paths, reflecting a lifelong learning concept. This article, taking the characteristics of e-commerce majors in vocational colleges as an example, and using CK Vocational College as a case study, delves into the OBE educational philosophy and analyzes the issues faced by the college in the practical teaching of e-commerce majors in four aspects: the definition of learning outcomes, the implementation process of practical teaching, the construction of an evaluation system for practical teaching effects, and the career planning of students. Additionally, this article designs a practical teaching model for talent cultivation in the e-commerce major at CK Vocational College, covering the definition of learning outcomes, implementation paths, outcome assessment, and feedback optimization.

Identification of homelessness using health administrative data in Ontario, Canada following a national coding mandate: a validation study

ObjectivesConducting longitudinal health research about people experiencing homelessness poses unique challenges. Identification through administrative data permits large, cost-effective studies; however, case validity in Ontario is unknown after a 2018 Canada-wide policy change mandating homelessness coding in hospital databases. We validated case definitions for identifying homelessness using Ontario health administrative databases after introduction of this coding mandate. Study Design and SettingWe assessed 42 case definitions in a representative sample of people experiencing homelessness in Toronto (n = 640) from whom longitudinal housing history (ranging from 2018 to 2022) was obtained, and a randomly selected sample of presumably housed people (n = 128,000) in Toronto. We evaluated sensitivity, specificity, positive and negative predictive values, and positive likelihood ratios to select an optimal definition, and compared the resulting true positives against false positives and false negatives to identify potential causes of misclassification. ResultsThe optimal case definition included any homelessness indicator during a hospital-based encounter within 180 days of a period of homelessness (sensitivity = 52.9%; specificity = 99.5%). For periods of homelessness with ≥1 hospital-based healthcare encounter, the optimal case definition had greatly improved sensitivity (75.1%) while retaining excellent specificity (98.5%). Review of false positives suggested that homeless status is sometimes erroneously carried forward in healthcare databases after an individual transitioned out of homelessness. ConclusionCase definitions to identify homelessness using Ontario health administrative data exhibit moderate to good sensitivity and excellent specificity. Sensitivity has more than doubled since the implementation of a national coding mandate. Mandatory collection and reporting of homelessness information within administrative data present invaluable opportunities for advancing research on the health and healthcare needs of people experiencing homelessness.

Advancing Predictive Maintenance with PHM-ML Modeling: Optimal Covariate Weight Estimation and State Band Definition under Multi-Condition Scenarios

The proportional hazards model (PHM) is a vital statistical procedure for condition-based maintenance that integrates age and covariates monitoring to estimate asset health and predict failure risks. However, when dealing with multi-covariate scenarios, the PHM faces interpretability challenges when it lacks coherent criteria for defining each covariate’s influence degree on the hazard rate. Hence, we proposed a comprehensive machine learning (ML) formulation with Interior Point Optimizer and gradient boosting to maximize and converge the logarithmic likelihood for estimating covariate weights, and a K-means and Gaussian mixture model (GMM) for condition state bands. Using real industrial data, this paper evaluates both clustering techniques to determine their suitability regarding reliability, remaining useful life, and asset intervention decision rules. By developing models differing in the selected covariates, the results show that although K-means and GMM produce comparable policies, GMM stands out for its robustness in cluster definition and intuitive interpretation in generating the state bands. Ultimately, as the evaluated models suggest similar policies, the novel PHM-ML demonstrates the robustness of its covariate weight estimation process, thereby strengthening the guidance for predictive maintenance decisions.

Human Behavior in Suboptimal Choice Tasks: Defining Optimality.

Suboptimal choice behavior, or behavior that leads to a loss of resources over time, has been observed in a laboratory setting from multiple species. A procedure commonly used to capture this effect involves presenting two alternatives during choice trials, one of which is optimal whereas the other is suboptimal. The optimal alternative yields reinforcement more often than the suboptimal alternative, but often does not produce signals that indicate whether reinforcement will occur. The suboptimal alternative produces less reinforcement than the optimal alternative but may include reinforcement-predictive stimuli that indicate to the organism whether reinforcement will occur. This procedural framework has consistently produced a preference for the suboptimal alternative in pigeons and, to a lesser extent, rats. However, human participants have demonstrated preference for the optimal alternative. Following a review of past suboptimal choice research, we applied the reinforcement-derived definition of optimality to two sets of our previously published human data. We found that under multiple conditions, human choice behavior was consistent with what was predicted by the proportion of obtained reinforcement, thus supporting that the behavior was optimal. However, we found that participants in two conditions chose the suboptimal alternative more than expected. This finding could be considered as a demonstration of suboptimal choice in humans. We propose that comparing choice behavior to what past obtained reinforcement outcomes would predict might be a more accurate view of whether patterns of choice are within the parameters of this task.

Type-specific whole blood still has a role in the era of low-titer O universal donor transfusion for severe trauma hemorrhage.

Whole blood can be ABO-type specific (type-specific whole blood (TSWB)) or low-titer O universal donor (low-titer O whole blood (LTOWB)). Having previously used LTOWB, the US Armed Forces Blood Program began using TSWB in 1965 as a method of increasing the donor pool. In contrast to military practice, the Association for the Advancement of Blood and Biotherapies formerly the American association of blood banks (AABB), from its first guidelines in 1958 until 2018, permitted only TSWB. Attempting to reduce time to transfusion, the US military reintroduced LTOWB in the deployed environment in 2015; this practice was endorsed by the AABB in 2018 and is progressively being implemented by military and civilian providers worldwide. Low-titer O whole blood is the only practical solution prehospital. However, there are several reasons to retain the option of TSWB in hospitals with a laboratory. These include (1) as-yet ill-defined risks of immunological complications from ABO-incompatible plasma (even when this has low titers of anti-A and -B), (2) risks of high volumes of LTOWB including published historical advice (based on clinical experience) not to transfuse type-specific blood for 2 to 3 weeks following a substantial LTOWB transfusion, (3) uncertainty as to the optimal definition of "low titer," and (4) expanding the potential donor pool by allowing type-specific transfusion. Several large randomized controlled trials currently underway are comparing LTOWB with component therapy, but none address the question of LTOWB versus TSWB. There are sufficient data to suggest that the additional risks of transfusing LTOWB to non-group O recipients should be avoided by using TSWB as soon as possible. Combined with the advantage of maintaining an adequate supply of blood products in times of high demand, this suggests that retaining TSWB within the civilian and military blood supply system is desirable. TSWB should be preferred when patient blood group is confirmed in facilities with a hematology laboratory, with LTOWB reserved for patients whose blood group is unknown.

Revealing risky mistakes through revisions

We argue that a choice that is modified, absent any informational change, is revealed to have been a mistake. In an experiment, we allow subjects to choose from budgets over binary lotteries. To identify mistakes, which we interpret as deviations from an underlying “true” preference, we allow subjects to revise a subset of their initial choices. The set of revised decisions improves under several standard definitions of optimality. These mistakes are prevalent: subjects modify over 75% of their initial choices when given the chance. Subjects make larger mistakes when inexperienced and when choosing over lotteries with small probabilities of winning.

Morphological optimization of butterfly-shaped inserts for heat transfer enhancement in tubular heat exchangers: a numerical study

Single-phase heat transfer enhancement in heat exchangers represents a crucial issue for effective thermal treatment in many industrial applications, especially when highly viscous fluids or gases are processed. Increase of heat transfer capabilities might be obtained by passive techniques, such as tube corrugations or static inserts promoting boundary layers disruption at the fluid-wall interface. Different inserts have been proposed for tubular heat exchangers over the past decades, including twisted tapes, wired coils, conical rings and butterfly-shaped geometries. However, the literature lacks optimal geometries definitions. The aim of the present work is to achieve a morphological optimization of a butterfly insert through an adjoint approach to maximize heat transfer over pressure losses in heat exchangers tubes. In the present investigation, conjugate conduction-convection heat transfer in the computational domain is solved through a steady RANS approach. Turbulence is treated by means of the Realizable k-ε model with enhanced wall function. The model is successfully validated against experimental data. The optimization results suggest a reduction of the opening angle of the butterfly inserts of about 22°. The reported remarks can be used as guidelines for fabrication of optimized designs in tubular heat exchangers applications.

Theoretical foundations of development and implementation of event projects for trade enterprises

The article is devoted to analyzing the essence of the concept of «event» and improving its classification and substantiation of the principles of its implementation through the stages of development of an event for trade enterprises. A morphological analysis of the concept of «event» is carried out by allocating the optimal definition. A primary classification of the concept of «event» (by planning) is proposed, where the planned event is defined, which is the subject of the study of event management. They require setup, guidance, managers, and a specific time. An unplanned event is an accident, natural disaster, and other similar events. The classification of events by size and scale has been improved, dividing them into mega, business cards, central, and local events. The main mistakes that are made when organizing an event are identified, which include the fact that the event is created only in order to hold it and then be proud, but at the same time, the event does not cover the target audience at all, or is devoid of meaningful meaning for it; And also when creating an event, the company is so fixated on its importance that it forgets about the interests of consumers. It is determined that the development of the event includes the definition of its structure, which includes planning meetings, the work of sections, the cultural program, and the duration of each stage. The second step is to choose the time and place of the event, which should consider the target audience, season, weather conditions, and parallel events because the wrong choice can affect attendance. As the final document, the event scenario should detail all aspects of the organization. The third stage involves the development of content and script, where all elements should be harmoniously combined. The role of information support in the event management of projects is outlined, outlining the need to inform the audience in advance about the event through various channels, depending on its format and scale. Keywords: event, events, technologies, event management, event project.

On cone-based decompositions of proper Pareto-optimality in multi-objective optimization

In recent years, research focus in multi-objective optimization has shifted from approximating the Pareto optimal front in its entirety to identifying solutions that are well-balanced among their objectives. Proper Pareto optimality is an established concept for eliminating Pareto optimal solutions that exhibit unbounded tradeoffs. Imposing a strict tradeoff bound in a classical definition of proper Pareto optimality allows specifying how many units of one objective one is willing to trade in for obtaining one unit of another objective. Recent studies have shown that this notion shows favorable convergence properties. One of the aims of this paper is to translate the proper Pareto optimality notion to an ordering relation, which we denote by M-domination. The mathematical properties of M-domination are thoroughly analyzed in this paper yielding key insights into its applicability as decision making aid and in designing population-based algorithms for solving multi-objective optimization problems. We complement our work by providing four different geometrical descriptions of the M-dominated space given by a union of polyhedral cones. A geometrical description does not only yield a greater understanding of the underlying tradeoff concept, but also allows a quantification of the hypervolume dominated by a particular solution or an entire set of solutions. These descriptions shall enable researchers to formulate hypervolume-based approaches for finding approximations of the Pareto front that emphasize regions that are well-balanced among their tradeoffs in subsequent works.

Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2.

Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature. The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators. This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non-BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies. The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.

Numerical investigation of the cavitation effects on the wake dynamics behind a blunt trailing edge hydrofoil

The influence of cavitation on the wake behind a NACA 0009 hydrofoil with a truncated trailing edge has been numerically investigated using a homogeneous mixture model coupled with a controlled decay SST γ-Reθt turbulence model. Using optimal definitions of the inlet turbulent intensity and the empirical condensation and vaporization coefficients of the cavitation model, simulated results have shown a good agreement with experimental data. Notably, the numerical results exhibit negligible deviations of less than 0.7% in vortex shedding frequencies for different cavitation levels. If the size of the vortex cavitation grows, a substantial increase in both lift and drag coefficients on the hydrofoil is observed. Furthermore, the influence of cavitation on the trajectories of vortex centers and the morphology of the primary shedding vortices has been revealed using a vortex identification method. The findings highlight that the cavitation development enhances the advected velocity of the shedding vortices while decreasing the streamwise inter-vortex spacing. Consequently, both factors are found to contribute to the increase of the vortex-shedding frequency behind the NACA 0009 hydrofoil with the truncated trailing edge when cavitation appears and develops.

Defining success after surgical treatment of stress urinary incontinence

BackgroundA consensus standardized definition of success after stress urinary incontinence surgical treatment is lacking, which precludes comparisons between studies and affects patient counseling. ObjectivesTo identify optimal patient-centric definition(s) of success after stress urinary incontinence surgical treatment and to compare the identified “more accurate” treatment success definitions with a commonly used composite definition of success (ie, no reported urine leakage, negative cough stress test result, and no retreatment). Study DesignWe evaluated 51 distinct treatment success definitions for participants enrolled in a previously conducted randomized trial of stress urinary incontinence treatments concomitantly performed with sacrocolpopexy (NCT00934999). For each treatment success definition, we calculated the mean (SD) of participant-assessed symptom improvement and participant-assessed surgical success scores with an 11-point Likert scale among those achieving success and failure. The “more accurate” treatment success definition(s) were identified by measuring the magnitude of the mean difference of participant assessments with Hedges g values. The treatment success definitions with the highest Hedges g values were considered “more accurate” treatment success definitions and were then compared with the composite definition of success. ResultsThe percentage of participants who had treatment success (6.4% to 97.3%) and Hedges g values (–4.85 to 1.25) varied greatly according to each treatment success definition. An International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score of 5 or less, Urogenital Distress Inventory-6 score of 33.3 or less, and a no/mild stress urinary incontinence response on Urogenital Distress Inventory-6 question 3 had the highest Hedges g values and were considered the top 3 “more accurate” treatment success definitions. Paradoxically, treatment success definitions that required a negative cough stress test result or no persistent urinary leakage greatly reduced the ability to differentiate participant-assessed symptom improvement or surgical success. When the “more accurate” treatment success definitions were compared with the composite definition, patients with failed treatment according to the composite definition had lower Urinary Impact Questionnaire-7 scores, and a higher proportion of complete/somewhat satisfaction and very good/perfect bladder condition survey responses. Additionally, the composite definition had considerably fewer favorable outcomes for participants than did the top 3 “more accurate” treatment success definitions. ConclusionsSuccessful outcomes of stress urinary incontinence surgical treatments for women undergoing concurrent sacrocolpopexy varied greatly depending on the definition used; however, stringent definitions (requiring complete dryness) and objective testing (negative cough stress test result) had decreased, rather than increased, participant-assessed symptom improvement and surgical success scores. The “more accurate” treatment success definitions better differentiated participant-assessed symptom improvement and surgical success than the composite definition. The composite definition disproportionally misidentified participants who reported minor symptoms or complete/somewhat satisfaction with their outcome as having treatment failures and yielded a considerably lower proportion of women who reported favorable outcomes than did the top 3 “more accurate” treatment success definitions.

P772 Comprehensive disease control in patients with Ulcerative Colitis: refinement of a multi-component endpoint using data from the filgotinib SELECTION trial

Abstract Background Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement. We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522). Methods CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP &amp;lt;150 µg/g, CDC4-150; CDC4 with FCP &amp;lt;250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP &amp;lt;150 µg/g, CDC5-150; and CDC5 with FCP&amp;lt;250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was visualized in UpSet plots. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components). Results At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve pMCS remission compared with 5.0%, 10.1% and 6.0% who did not achieve IBDQ remission, biomarker remission and endoscopic improvement, respectively (Figure). Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions. Conclusion CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.

Haze weather and mortality in China from 2014 to 2020: Definitions, vulnerability, and effect modification by haze characteristics

Haze weather, characterized by low visibility due to severe air pollution, has aroused great public concern. However, haze definitions are inconclusive, and multicentre studies on the health impacts of haze are scarce. We collected data on the daily number of deaths and environmental factors in 190 Chinese cities from 2014 to 2020. The city-specific association was estimated using quasi-Poisson regression and then pooled using meta-analysis. We found a negative association between daily visibility and non-accidental deaths, and mortality risk sharply increased when visibility was < 10 km. Haze weather, defined as a daily average visibility of < 10 km without a limit for humidity, produced the best model fitness and greatest effect on mortality. A haze day was associated with an increase of 2.53% (95% confidence interval [CI]:1.96, 3.10), 2.84 (95% CI: 2.13, 3.56), and 2.99% (95% CI: 1.94, 4.04) in all non-accident, cardiovascular and respiratory mortality, respectively. Haze had the greatest effect on lung cancer mortality. The haze-associated risk of mortality increased with age. Severe haze (visibility <2 km) and damp haze (haze with relative humidity >90%) had greater health impacts. Our findings can help in the development of early warning systems and effective public health interventions for haze.