Overlapping Confidence Intervals Research Articles

Bridging the notch: quantification of the end diastolic notch to better predict fetal growth restriction.

We aimed to evaluate several quantitative methods to describe the diastolic notch (DN) and compare their performance in the prediction of fetal growth restriction. Patients who underwent a placental scan at 16-26 weeks of gestation and delivered between Jan 2016 and Dec 2020 were included. The uterine artery pulsatility index was measured for all of the patients. In patients with a DN, it was quantified using the notch index and notch depth index. Odds ratios for small for gestational age neonates (defined as birth weight <10th and <5th percentile) were calculated. Predictive values of uterine artery pulsatility, notch, and notch depth index for fetal growth restriction were calculated. Overall, 514 patients were included, with 69 (13.4%) of them delivering a small for gestational age neonate (birth weight<10th percentile). Of these, 20 (20.9%) had a mean uterine artery pulsatility index >95th percentile, 13 (18.8%) had a unilateral notch, and 11 (15.9%) had a bilateral notch. 16 patients (23.2%) had both a high uterine artery pulsatility index (>95th percentile) and a diastolic notch. Comparison of the performance between uterine artery pulsatility, notch, and notch depth index using receiver operating characteristic curves to predict fetal growth restriction <10th percentile found area under the curve values of 0.659, 0.679, and 0.704, respectively, with overlapping confidence intervals. Quantifying the diastolic notch at 16-26 weeks of gestation did not provide any added benefit in terms of prediction of neonatal birth weight below the 10th or 5th percentile for gestational age, compared with uterine artery pulsatility index.

An evaluation of the replicability of analyses using synthetic health data

Synthetic data generation is being increasingly used as a privacy preserving approach for sharing health data. In addition to protecting privacy, it is important to ensure that generated data has high utility. A common way to assess utility is the ability of synthetic data to replicate results from the real data. Replicability has been defined using two criteria: (a) replicate the results of the analyses on real data, and (b) ensure valid population inferences from the synthetic data. A simulation study using three heterogeneous real-world datasets evaluated the replicability of logistic regression workloads. Eight replicability metrics were evaluated: decision agreement, estimate agreement, standardized difference, confidence interval overlap, bias, confidence interval coverage, statistical power, and precision (empirical SE). The analysis of synthetic data used a multiple imputation approach whereby up to 20 datasets were generated and the fitted logistic regression models were combined using combining rules for fully synthetic datasets. The effects of synthetic data amplification were evaluated, and two types of generative models were used: sequential synthesis using boosted decision trees and a generative adversarial network (GAN). Privacy risk was evaluated using a membership disclosure metric. For sequential synthesis, adjusted model parameters after combining at least ten synthetic datasets gave high decision and estimate agreement, low standardized difference, as well as high confidence interval overlap, low bias, the confidence interval had nominal coverage, and power close to the nominal level. Amplification had only a marginal benefit. Confidence interval coverage from a single synthetic dataset without applying combining rules were erroneous, and statistical power, as expected, was artificially inflated when amplification was used. Sequential synthesis performed considerably better than the GAN across multiple datasets. Membership disclosure risk was low for all datasets and models. For replicable results, the statistical analysis of fully synthetic data should be based on at least ten generated datasets of the same size as the original whose analyses results are combined. Analysis results from synthetic data without applying combining rules can be misleading. Replicability results are dependent on the type of generative model used, with our study suggesting that sequential synthesis has good replicability characteristics for common health research workloads.

Model-averaging as an accurate approach for ex-post economic optimum nitrogen rate estimation

AbstractFinding economic optimum fertilizer rate with good accuracy is essential for optimal crop yield, efficient resource utilization, and environmental well-being. However, the prevailing incomplete understanding of input-output relationships leads to imprecise crop yield response functions, such as those for winter wheat, and potentially biased fertilizer choices. From a statistical point of view, there is uncertainity with regards to which model is most suitable to estimate the economic optimum fertilizer rate. This complexity is amplified when considering site-specific nitrogen fertilization, which factors into elements like soil attributes, topography, and crop variations within a field, as opposed to uniform application. This study undertakes a comparative analysis to evaluate biases, variance, mean squared errors and confidence intervals in Economic Optimum Nitrogen Rate (EONR) estimations across different functional forms. The goal is to uncover performance discrepancies among these forms and explore potential advantages of adopting model averaging for optimizing nitrogen use in crop cultivation. The results of simulations reveal noteworthy biases when comparing diverse yield functions with the averaged model, particularly evident in the Linear-Plateau and Mitscherlich models. Moreover, analysis of empirical data indicates that confidence intervals for the averaged model overlap with the projected ranges of all functions. This implies that the averaged model could be suitable for determining EONR and effectively address the problem of model specification without focusing on one specific functional form. The effectiveness of model averaging hinges on incorporating models that well approximate the true model. However, even if the true model is not known, the average model can provide reasonable information for determining the EONR, provided that similar model specifications are considered. This has implications for modelling of yield response for various applications and can contribute to unbiased estimations of yield response.

Rethinking the definition of stage IV disease in adrenocortical carcinoma: Assessing the impact of clinical lymph node positive disease.

5 Background: Stage III (pT3N0M0 or pT1-3N1M0) adrenocortical carcinoma (ACC) encompasses both lymph node positive (LN+) and lymph node negative (LN-) disease. However, in other malignancies, prior data demonstrates that LN+ disease portends outcomes similar to metastatic, stage IV disease. We similarly wanted to examine the impact of clinical LN+ disease on oncologic outcomes in ACC. Methods: Patients with clinical stage III and stage IV (M1) disease were identified using the National Cancer Database (NCDB). Stage III patients were stratified as having either LN+ or LN- disease. Kaplan-Meier curves illustrated overall survival of the three groups – stage III LN-, stage III LN+, and stage IV. Further analysis stratified stage III LN+ and stage IV patients by whether or not patients received treatment (systemic therapy, surgery, or both). Results: A total of 917 patients were included in the analysis – 322 stage III LN-, 67 stage III LN+, and 528 stage IV. 3-year OS for patients with stage IV, stage III LN+, and stage III LN – was 15.6% (95% CI, 12.5%-19.4%), 29.4% (95% CI, 19.8%-43.6%), and 48.6% (95% CI, 43.2%-54.6%), respectively. Within the stage III LN+ group 3-year OS was 33.0% (95% CI, 18.5%-58.8%) for those who received treatment and was 27.4% (95% CI, 16.1% - 46.6%) for those who did not. Within the stage IV group 3-year OS was 29.8% (95% CI, 22.7%-39.3%) for those who received treatment and was 10.2% (95% CI, 7.4% - 14.2%) for those who did not. Conclusions: The current staging paradigm of ACC includes LN+ disease as part of the stage III classification. Herein, we see that clinical stage III LN+ disease had a 3-year OS that was more similar to clinical stage IV disease than clinical stage III LN- disease. While the survival curves appear distinct, due to the rarity of the disease and therefore small sample size there was overlapping confidence intervals. In stage IV patients there was a significant difference in OS at 3 years between those who did and did not receive treatment. This same finding was not found in stage III LN + patients.

Risk factors for and outcomes of ring expulsions with a 1-year contraceptive vaginal system

The US Food and Drug Administration-approved segesterone acetate and ethinyl estradiol ring-shaped contraceptive vaginal system, known as Annovera (Sever Pharma Solutions/QPharma, Malmö, Sweden), was inserted and removed under a woman's control for a 21 day in and 7 day out regimen for up to 13 cycles of use. We aimed to describe the patterns of ring expulsion over time, to identify potential predictors of expulsion, and to evaluate the impact of expulsions on method discontinuation and pregnancy risk. Using data from 2064 participants who were enrolled in 2 multinational phase 3 clinical trials on the use of this contraceptive vaginal system, we examined data from participants' daily diaries for documentation of complete ring expulsion. We modeled the odds of reported expulsions over time with adjustment for background and demographic characteristics using mixed-effects logistic regression models with random intercepts. We compared the probability of continuation between those who did and those who did not report expulsions in the first cycle of use using survival analysis and hazards modeling. To determine if expulsions during the first cycle of use affected the risk for pregnancy, we calculated Pearl Indices. Most participants (75%) never experienced any expulsions during any cycle of use, and 91% to 97% did not experience an expulsion during any 1 cycle. The incidence of expulsion was highest in cycle 1 (9%). The odds of experiencing expulsions decreased by half in cycles 2 to 8 when compared with cycle 1 (0.48; 95% confidence interval, 0.40-0.58), and in cycles 9 to 13, expulsions were about a third of that in cycle 1 (0.32; 95% confidence interval, 0.26-0.41). Of those who did experience expulsions, most (62%-84%) experienced ≤2 expulsions per cycle. Participants from study sites in Latin America vs those in the United States had higher odds of not experiencing an expulsion (odds ratio, 1.95; 95% confidence interval, 1.45-2.63). Women with a higher education level had higher odds of experiencing an expulsion. Notably, parity, age, and body mass index were not associated with expulsion. Participants who experienced any expulsions in cycle 1 were more likely to discontinue use early (hazard ratio, 1.28; 95% confidence interval, 1.14-1.43) than participants who did not have an expulsion. The Pearl Index for participants who had expulsions during cycle 1 was 3.99 (95% confidence interval, 1.29-9.31), which was higher than that among participants who reported no expulsions (Pearl Index, 2.39; 95% confidence interval, 1.61-3.41), but the overlapping confidence intervals indicate that there is not sufficient evidence to demonstrate an association between expulsions and pregnancy risk. Expulsions were infrequent overall, decreased with subsequent cycles of use, and were not associated with body mass index or parity. Early discontinuation of product use was higher among participants who experienced an expulsion during cycle 1. Although it is unclear whether pregnancy risk was associated with expulsions, early recognition of expulsions among users may identify those at higher risk for discontinuation and may highlight when enhanced anticipatory counselling and guidance may be advantageous.

P1018 Population pharmacokinetic and exposure-response analyses for efficacy and safety of risankizumab in subjects with moderately to severely active Ulcerative Colitis

Abstract Background Risankizumab (RZB) has been evaluated in subjects with moderately to severely active ulcerative colitis (UC) in the INSPIRE and COMMAND trials. Population pharmacokinetic (PPK) and exposure-response (ER) analyses were conducted at the end of Phase 2b and following Phase 3 to characterize RZB PK and its relationship with clinical efficacy and safety to support Phase 3 induction dose selection, and the final dose recommendations for induction and maintenance treatment. Methods PPK analyses in UC used a previously developed PPK model for Crohn’s disease with additional evaluation of covariates relevant to UC. ER relationships between RZB exposures and efficacy endpoints at the end of induction (Week 12), re-induction (Week 24; exploratory only) and maintenance (Week 52) periods were established using exploratory graphical analyses and logistic regression modeling. ER analyses for safety were performed for key variables through Weeks 12, 24 and 52 using graphical analyses. Results A two-compartment model with first-order absorption for SC administration and first-order elimination adequately described RZB PK. Among the various covariates assessed, body weight, baseline (BL) serum albumin, BL high-sensitivity C-reactive protein, BL fecal calprotectin, sex, advanced therapy IR status, BL pancolitis and corticosteroid use were statistically correlated with RZB clearance but their impact on exposure was not clinically relevant for efficacy. ER analyses for efficacy using Phase 2b induction data showed that while incremental improvement in efficacy was predicted with doses increasing from 1200 to 1800 mg, the magnitude of difference in efficacy was modest especially for endoscopy-driven endpoints. Phase 3 ER analyses for efficacy showed statistically significant trends of exposure-dependent increase in efficacy following induction treatment with 1200 mg IV at Week 0, 4 and 8, with greater response rates observed with higher exposures across all evaluated endpoints at Week 12, in line with the results from Phase 2b. ER analyses for maintenance demonstrated an exposure-dependent increase in efficacy for Week 52 endpoints, with modest improvement in efficacy when increasing the dose from 180 mg to 360 mg, and largely overlapping confidence intervals. ER analyses for safety indicated no apparent exposure-dependent safety events over the induction or maintenance treatment. Conclusion The PPK and ER analyses of RZB in subjects with UC characterized the disposition of RZB and its relationship to efficacy and safety, as well as the lack of impact by intrinsic and extrinsic factors on PK and efficacy. Results supported the final dosing regimen recommendations for the treatment of moderately to severely active UC.

Biomarkers for neurodegeneration impact cognitive function: a longitudinal 1-year case–control study of patients with bipolar disorder and healthy control individuals

BackgroundAbnormalities in cerebrospinal fluid (CSF)-amyloid-beta (Aβ)42, CSF-Aβ40, CSF-Aβ38, CSF-soluble amyloid precursor proteins α and β, CSF-total-tau, CSF-phosphorylated-tau, CSF-neurofilament light protein (NF-L), CSF-neurogranin, plasma-Aβ42, plasma-Aβ40, plasma-total-tau, plasma-NF-L and, serum-S100B during affective episodes may reflect brain changes that could impact cognitive function in patients with bipolar disorder (BD). The study aimed to investigate the association between these biomarkers indicative of Alzheimer’s disease and those reflecting neurodegeneration alongside their impact on cognitive function in patients with BD and healthy control individuals (HC). The primary hypothesis was that GL and VL would increase with increasing levels of CSF-Aβ42 based on data from T0 and T3 in BD and HC jointly.MethodsIn a prospective, longitudinal case–control study euthymic patients with BD (N = 85) and HC (N = 44) were evaluated with clinical assessment and neuropsychological testing at baseline (T0) and during euthymia after a year (T3). Patients’ affective states were recorded weekly as euthymic, subthreshold level, major depression, or (hypo)mania. If an episode occurred during follow-up, the patient was also assessed in post-episode euthymia. Cognitive performance was measured as a global cognitive score (GL) for four cognitive domains including verbal learning and memory (VL).ResultsEstimated in a linear mixed model GL increased with 0.001 for each increase of 1 pg/ml of CSF-Aβ42 (97.5%, CI 0.00043–0.0018, adjusted-p = 0.0005) while VL increased by 0.00089 (97.5%, CI 0.00015–0.0018, adjusted-p = 0.045) in BD and HC jointly. The association was weak, however stronger in patients with BD compared to HC. Associations between other biomarkers including CSF-neurogranin, and cognitive domains were overall weak, and none remained significant after adjustment for multiple testing.LimitationsModest sample size. A complete data set regarding both CSF-AB-42 and cognitive test scores was obtained from merely 61 patients with BD and 38 HC individuals.ConclusionCSF-Aβ42 may be associated with cognitive dysfunction in patients with BD and HC individuals. The association appeared to be stronger in BD but with overlapping confidence intervals. Hence it remains uncertain whether the association is a general phenomenon or driven by BD.

A Retrospective Study on Unveiling Demographic Trends and Clinical Significance for COVID-19 Patients in Tobruk City Hospital.

This study investigates the impact of COVID-19 within the Tobruk Medical Center community, focusing on prevalence, clinical traits, and mortality rates. A comprehensive analysis was conducted on a cohort of 435 COVID-19 positive hospitalized patients from 2020 to 2022.Result Our findings reveal a higher incidence of COVID-19 among men, particularly in the 60-80 age group. Notable comorbidities, including diabetes and hypertension, underscore the vulnerability of individuals with underlying health conditions. Mortality rates, slightly higher at Tobruk Medical Center, show overlapping confidence intervals, emphasizing the need for cautious interpretation.Conclusion The study provides crucial insights into demographic patterns and comorbidities affecting COVID-19 outcomes. The identification of risk factors, particularly the significant role of diabetes, contributes to our understanding of underlying health conditions in managing cases. Despite a slightly higher mortality rate at the medical center, the non-significant difference highlights the importance of considering potential limitations. This research contributes valuable information for guiding public health decisions and future pandemic responses, emphasizing the need for targeted interventions for at-risk populations.In conclusion, our study offers a nuanced understanding of the impact of COVID-19, providing essential knowledge to healthcare practitioners, policymakers, and researchers addressing the ongoing challenges posed by the pandemic.

Identifying Rare Genetic Determinants for Improved Polygenic Risk Prediction of Bone Mineral Density and Fracture Risk.

Osteoporosis and fractures severely impact the elderly population. Polygenic risk scores for bone mineral density have demonstrated potential clinical utility. However, the value of rare genetic determinants in risk prediction has not been assessed. With whole-exome sequencing data from 436,824 UK Biobank participants, we assigned White British ancestry individuals into a training data set (n = 317,434) and a test data set (n = 74,825). In the training data set, we developed a common variant-based polygenic risk score for heel ultrasound speed of sound (SOS). Next, we performed burden testing to identify genes harboring rare determinants of bone mineral density, targeting influential rare variants with predicted high deleteriousness. We constructed a genetic risk score, called ggSOS, to incorporate influential rare variants in significant gene burden masks into the common variant-based polygenic risk score. We assessed the predictive performance of ggSOS in the White British test data set, as well as in populations of non-White British European (n = 18,885), African (n = 7165), East Asian (n = 2236), South Asian (n = 9829), and other admixed (n = 1481) ancestries. Twelve genes in pivotal regulatory pathways of bone homeostasis harbored influential rare variants associated with SOS (p < 5.5 × 10-7 ), including AHNAK, BMP5, CYP19A1, FAM20A, FBXW5, KDM5B, KREMEN1, LGR4, LRP5, SMAD6, SOST, and WNT1. Among 4013 (5.4%) individuals in the test data set carrying these variants, a one standard deviation decrease in ggSOS was associated with 1.35-fold (95% confidence interval [CI] 1.16-1.57) increased hazard of major osteoporotic fracture. However, compared with a common variant-based polygenic risk score (C-index = 0.641), ggSOS had only marginally improved prediction accuracy in identifying at-risk individuals (C-index = 0.644), with overlapping confidence intervals. Similarly, ggSOS did not demonstrate substantially improved predictive performance in non-European ancestry populations. In summary, modeling the effects of rare genetic determinants may assist polygenic prediction of fracture risk among carriers of influential rare variants. Nonetheless, improved clinical utility is not guaranteed for population-level risk screening. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Prediction Model with Validation for Polioseronegativity in Malnourished Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Malnutrition is identified as a risk factor for insufficient polio seroconversion in the context of a vaccine-derived poliovirus (VDPV) outbreak-prone region. In the Democratic Republic of Congo (DRC), underweight decreased from 31% (in 2001) to 26% (in 2018). Since 2004, VDPV serotype 2 outbreaks (cVDPV2) have been documented and were geographically limited around the Haut-Lomami and Tanganyika Provinces. To develop and validate a predictive model for poliomyelitis vaccine response in malnourished infants, a cross-sectional household study was carried out in the Haut-Lomami and Tanganyika provinces. Healthy children aged 6 to 59 months (n=968) were enrolled from eight health zones (HZ) out of 27, in March 2018. We performed a bivariate and multivariate logistics analysis. Final models were selected using a stepwise Wald method, and variables were selected based on the criterion p < 0.05. The association between nutritional variables, explaining polio seronegativity for the three serotypes, was assessed using the receiver operating characteristic curve (ROC curve). Factors significantly associated with seronegativity to the three polio serotypes were underweight, non-administration of vitamin A, and the age group of 12 to 59 months. The sensitivity was 10.5%, and its specificity was 96.4% while the positive predictive values (PPV) and negative (PNV) were 62.7% and 65.3%, respectively. We found a convergence of the curves of the initial sample and two split samples. Based on the comparison of the overlapping confidence intervals of the ROC curve, we concluded that our prediction model is valid. This study proposed the first tool which variables are easy to collect by any health worker in charge of vaccination or in charge of nutrition. It will bring on top, the collaboration between the Immunization and the Nutritional programs in DRC integration policy, and its replicability in other low- and middle-income countries with endemic poliovirus.

THU031 White Blood Cells (WBC) As Biological Markers Of Cortisol Status In Patients With Cushing's Disease (CD)

Abstract Disclosure: B.M. Mascarenhas-Nakano: None. P.F. Santos-Neto: None. L.C. Portari: None. S.R. Correa-Silva: None. J. Abucham: None. CD is a rare disease caused by ACTH-secreting pituitary adenomas and responsible for ∼80% of cases of endogenous hypercortisolism. Hypercortisolism affects all tissues, leading to several nonspecific and few specific anatomical and functional changes which are not always easy to recognize and quantify. Clinical suspicion is the first step in the diagnosis but is rather impressionistic. The influence of endogenous cortisol on WBC, recognized a long time ago, has been widely forgotten/ignored in clinical practice. In this study, we aimed to assess the potential of WBC as biological markers of cortisol status in patients with CD. Patients and Methods: We retrospectively compared Leukocyte (Le), Neutrophil (Ne), Lymphocyte (Ly), Monocyte (Mo), Eosinophil (Eo), and Basophil (Ba) counts at diagnosis in patients with proven CD (CDdx, n=64), at remission after treatment (pituitary surgery, adrenalectomy, or radiotherapy) (CDrem=36), and in a control group of patients with hypercortisolism suspected and ruled out using ES guidelines (CT, n=63). In addition, we retro-prospectively evaluated WBC in a subgroup of 33 patients before and after treatment [25 in remission (RE) and 8 in non-remission (NRE)]. Comparisons &amp;gt;2 groups: ANOVA followed by multiple comparison tests (MCT). Before vs after comparisons: paired tests. Variations (Δ= after-before) between different groups: unpaired tests. Associations: Fisher´s exact test. ROC curves were generated cut off values chosen by Youden index. Significance was set at 0.05. Results: At Diagnosis. Le, Ne, Ly, and Mo were increased and Ly decreased: CDdx vs CT (0.0075&amp;lt;P&amp;lt;0.0001), CDdx vs CDre (0.0015&amp;lt;P&amp;lt;0.0001), CDre vs CT (0.34&amp;lt;P&amp;lt;0.99). Eo and Ba showed no differences in CDdx vs CT (0.20&amp;lt;P&amp;lt;0.67). Diagnostic ROC curves were significant (0.047&amp;lt;P&amp;lt;0.0001) for all cells and various indexes (ratios and differences). AUC (0.8705), Youden index (0.696)(cut off 3,047), sensitivity (87.3%), specificity (82.26%), PPV (0.83) and NPV (0.86) were all highest for the difference Ne-Ly with overlapping confidence intervals with other indexes. At Remission. In paired analysis, most cells showed significant changes after remission. However, comparisons of Δs between RE and NRE groups were only significant for ΔLy and ΔNe% [nearly significant (P=0.06) for ΔNe%-Ly% and ΔLy%]. Remission was associated with ΔLy&amp;gt;-3 (P=0.0049) and ΔNe%&amp;lt;-12.5% (P=0.0463). Combining both parameters (ΔLy&amp;gt;-3 and/or ΔNe%&amp;lt;-12.5%), a stronger association (P= 0.0001) was found. Evaluation of cortisol status after treatment using the combined criterion was able to identify 21/25 (84%) patients in remission and 8/8(100%) innon-remission. Conclusions: Our results show that WBC, mainly Ne and Ly, are reliable biological markers of cortisol status and potentially useful in different steps of the diagnosis of endogenous hypercortisolism as well as in the follow up of patients with CD after treatment. Presentation: Thursday, June 15, 2023

Single-dose Effectiveness of Mpox Vaccine in Quebec, Canada: Test-negative Design With and Without Adjustment for Self-reported Exposure Risk.

During the 2022 mpox outbreak, the province of Quebec, Canada, prioritized first doses for pre-exposure vaccination of people at high mpox risk, delaying second doses due to limited supply. We estimated single-dose mpox vaccine effectiveness (VE) adjusting for virus exposure risk based only on surrogate indicators available within administrative databases (eg, clinical record of sexually transmitted infections) or supplemented by self-reported risk factor information (eg, sexual contacts). We conducted a test-negative case-control study between 19 June and 24 September 2022. Information from administrative databases was supplemented by questionnaire collection of self-reported risk factors specific to the 3-week period before testing. Two study populations were assessed: all within the administrative databases (All-Admin) and the subset completing the questionnaire (Sub-Quest). Logistic regression models adjusted for age, calendar-time and exposure-risk, the latter based on administrative indicators only (All-Admin and Sub-Quest) or with questionnaire supplementation (Sub-Quest). There were 532 All-Admin participants, of which 199 (37%) belonged to Sub-Quest. With exposure-risk adjustment based only on administrative indicators, single-dose VE estimates were similar among All-Admin and Sub-Quest populations at 35% (95% confidence interval [CI]:-2 to 59) and 30% (95% CI:-38 to 64), respectively. With adjustment supplemented by questionnaire information, the Sub-Quest VE estimate increased to 65% (95% CI:1-87), with overlapping confidence intervals. Using only administrative data, we estimate one vaccine dose reduced the mpox risk by about one-third; whereas, additionally adjusting for self-reported risk factor information revealed greater vaccine benefit, with one dose instead estimated to reduce the mpox risk by about two-thirds. Inadequate exposure-risk adjustment may substantially under-estimate mpox VE.

207 Does Adjuvant Radiotherapy Lead to Increased Survival in Patients with Adenoid Cystic Carcinoma of the Breast? a Systematic Review and Meta-Analysis

Abstract Aim Adenoid cystic carcinoma (ACC) of the breast accounts for approximately 0.1% of all breast tumours (Zhang et al, 2021). The aim of this systematic review and meta-analysis was to determine whether adjuvant radiotherapy provides an additional benefit when compared to surgery alone in terms of overall survival in patients with ACC. Method A total of 3,330 records were identified and screened following database, conference proceedings, and currently registered studies search. Data from 5 case series was extracted. A random-effects meta-analysis of overall survival (OS) at 1, 2, 3-, 4-, 5- and 10-years post-intervention was performed. Results Adjuvant radiotherapy and surgery alone led to similar OS at all points post-intervention. For instance, 5-year survival following use of adjuvant radiotherapy was 92.8% (95% CI: 90.5%-94.7%), compared to 88.7% (95% CI: 81.9%-94.2%) with surgery alone. The confidence intervals overlap, which was the case for all points post-intervention. Conclusions Similar OS for both adjuvant radiotherapy and surgery alone (and overlapping confidence intervals), suggest the former may not provide an additional benefit in terms of OS in patients with ACC. Considering the negative side effects of radiotherapy, it could be argued that surgery alone should be used for the treatment ACC. However, this conclusion is hindered by the low number of studies included in this meta-analysis and their low level of evidence. This could be attributed to the low incidence of ACC. Further data should be collected to more reliably determine their optimal treatment.

Performance of a Support Vector Machine Learning Tool for Diagnosing Diabetic Retinopathy in Clinical Practice.

To examine the real-world performance of a support vector machine learning software (RetinaLyze) in order to identify the possible presence of diabetic retinopathy (DR) in patients with diabetes via software implementation in clinical practice. 1001 eyes from 1001 patients-one eye per patient-participating in the Danish National Screening Programme were included. Three independent ophthalmologists graded all eyes according to the International Clinical Diabetic Retinopathy Disease Severity Scale with the exact level of disease being determined by majority decision. The software detected DR and no DR and was compared to the ophthalmologists' gradings. At a clinical chosen threshold, the software showed a sensitivity, specificity, positive predictive value and negative predictive value of 84.9% (95% CI: 81.8-87.9), 89.9% (95% CI: 86.8-92.7), 92.1% (95% CI: 89.7-94.4), and 81.0% (95% CI: 77.2-84.7), respectively, when compared to human grading. The results from the routine screening were 87.0% (95% CI: 84.2-89.7), 85.3% (95% CI: 81.8-88.6), 89.2% (95% CI: 86.3-91.7), and 82.5% (95% CI: 78.5-86.0), respectively. AUC was 93.4%. The reference graders Conger's Exact Kappa was 0.827. The software performed similarly to routine grading with overlapping confidence intervals, indicating comparable performance between the two groups. The intergrader agreement was satisfactory. However, evaluating the updated software alongside updated clinical procedures is crucial. It is therefore recommended that further clinical testing before implementation of the software as a decision support tool is conducted.

Surgical management of bifocal femoral fractures: a systematic review and pooled analysis of treatment with a single implant versus double implants

IntroductionFractures of the proximal femur accompanied by a fracture of the femoral shaft are relatively rare, with a reported prevalence between 1 and 12%. Multiple surgical options are available, consisting of treatment with a single implant or with double implants. Controversy exists about the optimal management. A systematic review and pooled analysis were performed to assess the most reliable treatment for bifocal femoral fractures of the femur.Materials and methodsA literature search was conducted on July 15, 2022. Selected studies were screened on title and abstract by two researchers independently, and full texts were read by both authors. Emphasis was put on adverse events such as postoperative infection, healing complications, malalignment, and functional outcome using either a single implant or double implants.ResultsFor the proximal femoral fractures, no significant difference could be confirmed for avascular necrosis of the femoral neck (5.1% for single implant and 3.8% for double implants), nonunion (6.4% for single implant and 7.8% for double implants), or varus malalignment (6.6% for single implant and 10.9% for double implants). This study also suggests that the number of implants is irrelevant for complications of the femoral shaft regarding the rates of postoperative infection and healing complications. Pooled rates of bone healing complications were 1.6–2.7-fold higher when patients were treated with a single implant, but statistical significance could not be confirmed. For hardware failure, revision surgery, leg length discrepancy, and functional outcome, no difference between the two groups was found either.ConclusionsThe pooled proportions of all postoperative complications had overlapping confidence intervals; thus, no inference about a statistically significant difference on the number of implants used for treating ipsilateral fractures of the femur can be made. Both treatment groups showed a similar functional outcome at the last moment of follow-up, with more than 75% of the patients reporting a good outcome.

Is There Any Association between Nutrition and Myopia?: A Systematic Review.

This systematic review indicates that the current evidence shows no association of nutrition with myopia. We systematically reviewed the outcomes of the studies that previously investigated the association between nutrition and myopia. Embase, MEDLINE, and PubMed were searched by two independent authors to identify cross-sectional, cohort, retrospective, or interventional studies that assessed the association of nutrition with myopia from inception to the year 2021. Further, the reference list of the included articles was screened. The data from the included studies were extracted and qualitative analysis was performed. Quality assessment for non-interventional studies and interventional trials was performed using the Newcastle-Ottawa scale and Cochrane RoB 2 respectively. Twenty-seven articles were included in the review. Most of the nutrients and dietary elements investigated in non-interventional studies showed inconsistencies in their association with myopia with the majority indicating no association. Nine studies showed a significant association of diverse nutrients and dietary elements with either an increase (Odds ratio: 1.07) or a decrease (Odds ratio: 0.5 to 0.96) in the risk of myopia development. However, the majority of these studies have minimal odds ratios with wider or overlapping confidence intervals, implicating weaker associations. All three nutrients and dietary elements assessed in the interventional trial had implications for myopia control, with two trials indicating a clinically minimal effect. This review implies that there is some evidence to indicate a potential influence of specific nutrients and dietary elements in myopia development which are supported by several theories. However, given the vast, diverse, and complex nature of nutrition, more systematic investigation is warranted to comprehend the extent to which these specific nutrients and dietary elements are associated with myopia through longitudinal studies by subduing the limitations in the existing literature.

Can synthetic data accurately mimic oncology clinical trials?

1554 Background: There is strong interest by researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data. Reusing data extracts the most utility possible from patient contributions. The majority of patients do want to share their data for secondary research purposes. However, data access for secondary analysis remains a challenge. A key reason why individual-level data is not made directly available to data users by authors and data custodians is concern over breaches of patient privacy. Synthetic data generation (SDG) is an effective way to address privacy concerns that can enable the broader sharing of clinical trial datasets. However, a key question is whether the reproducibility of the generated data is adequate to draw reliable conclusions. Methods: We synthesized datasets from five pragmatic breast cancer clinical trials performed by the REaCT group (https://react.ohri.ca/). A sequential synthesis method, a type of machine learning was performed. The published analysis of each trial was repeated on each synthetic dataset to evaluate reproducibility. We evaluated reproducibility on three criteria: (a) decision agreement: the direction and statistical significance of the primary endpoint effect estimates are the same as the real data, (b) estimate agreement: the parameter estimates from the synthetic data are within the 95% confidence interval of the real data, and (c) the confidence interval overlap between real and synthetic parameters is above 50%. In addition, we evaluated privacy using a membership disclosure metric. This evaluates the ability of an adversary to determine that a target individual was in the original dataset using the synthetic data, computed as an F1 classification accuracy score. Results: Our results show that decision and estimate agreements held true across all five trials, and the confidence interval overlap was high. The risks of membership disclosure are all below the established 0.2 threshold. Conclusions: In this study, we were able to successfully generate synthetic datasets that accurately replicated original data from 5 oncology trials and yielded the same results as in the original published studies, with a very low risk of membership disclosure. With proper modeling techniques, synthetic datasets can play a key role in data democratization and the reuse of oncology clinical trials.[Table: see text]

Slow information processing speed elucidates impairment in executive function tests in people with Multiple Sclerosis (P13-3.008)

<h3>Objective:</h3> Analyze the association between performance on speeded and nonspeeded tasks of executive functions (EFs) and slow information processing speed (IPS) in people with Multiple Sclerosis (PwMS). <h3>Background:</h3> IPS and EFs are impaired domains in PwMS. However, it is unclear if executive deficits can be explained by slow IPS. <h3>Design/Methods:</h3> 74 PwMS were included (RR=86.2%, PP=4.3%, SP=9.6%; 74% female; age: 46.12±12.48 years; Physical disability (EDSS): 3.60±2.57; disease duration: 14.85±10.69 years). Measures: IPS: Symbol Digit Modalities Test; EFs: Speeded task of cognitive flexibility (Verbal Fluency), nonspeeded task of cognitive flexibility (Brixton Spatial Anticipation Test), nonspeeded task of working memory (Verbal Backward Digit Span); Clinical variables: EDSS, Fatigue Severity Scale and Beck Depression Inventory-II. A probit regression was performed, the results are shown in predicted probabilities format. <h3>Results:</h3> 47% of PwMS have slow IPS. IPS was associated with EDSS and all EFs measures (<i>p</i>=0.00) and did not correlated with fatigue and depression (<i>p</i>&gt;0.05). For the regression model, IPS, EDSS and EFs tasks were analyzed. Brixton and backward span tests lost significance when physical disability was controlled. Finally, the regression model had verbal fluency (Coefficient:-.49;<i>p</i>=0.001) and physical disability (Coefficient:.21; <i>p</i>=0.02) as independent variables. R²28%. Prob.chi2=0.00. For the predicted probabilities, verbal fluency was divided into 4 groups, controlling physical disability, and it was found that the probability of having poor verbal fluency with poor IPS is very high in the 1st and 2nd groups (.89 and .68, lowest confidence interval 0.53) and the probability of having high verbal fluency and slow IPS is very low in the 3th and 4th groups (.38 and .14, highest confidence interval 0.50), with no overlapping confidence intervals. Correctly classified 72%. <h3>Conclusions:</h3> Impairments on speeded task of EFs can be associated with slow IPS. It is important to include speeded and unspeeded tasks in the assessment of EFs to capture the effective deficit. <b>Disclosure:</b> Maria Sol Román has nothing to disclose. Miss Bardoneschi has nothing to disclose. Ms. Gatti has nothing to disclose. Mrs. De Los Santos has nothing to disclose. Mr. Iglesias Passada has nothing to disclose. Miss Daniele has nothing to disclose. Maria Laura Saladino has nothing to disclose. Fernando Caceres has nothing to disclose. Sandra Vanotti has received research support from Merck S.A.,Buenos Aires, Argentina, an affiliate Merck S.A.,Buenos Aires, Argentina, an affiliate of Merck KGaA, Darmstadt, Germany Merck KGaA, Darmstadt, Germany.

MP64-19 IMPACT OF NUMBER OF POSITIVE LYMPH NODES ON PROGNOSTIC STRATIFICATION IN RENAL CELL CARCINOMA: ANALYSIS OF THE NATIONAL CANCER DATABASE

You have accessJournal of UrologyCME1 Apr 2023MP64-19 IMPACT OF NUMBER OF POSITIVE LYMPH NODES ON PROGNOSTIC STRATIFICATION IN RENAL CELL CARCINOMA: ANALYSIS OF THE NATIONAL CANCER DATABASE Luke Wang, Florin Vaida, Dhruv Puri, Sohail Dhanji, Franklin Liu, Jonathan Afari, Margaret Meagher, Kevin Hakimi, Mimi Nguyen, Cesare Saitta, Saeed Ghassemzadeh, Aastha Shah, Ryan Nasseri, Juan Javier-Desloges, James Murphy Mckay, and Ithaar Derweesh Luke WangLuke Wang More articles by this author , Florin VaidaFlorin Vaida More articles by this author , Dhruv PuriDhruv Puri More articles by this author , Sohail DhanjiSohail Dhanji More articles by this author , Franklin LiuFranklin Liu More articles by this author , Jonathan AfariJonathan Afari More articles by this author , Margaret MeagherMargaret Meagher More articles by this author , Kevin HakimiKevin Hakimi More articles by this author , Mimi NguyenMimi Nguyen More articles by this author , Cesare SaittaCesare Saitta More articles by this author , Saeed GhassemzadehSaeed Ghassemzadeh More articles by this author , Aastha ShahAastha Shah More articles by this author , Ryan NasseriRyan Nasseri More articles by this author , Juan Javier-DeslogesJuan Javier-Desloges More articles by this author , James Murphy MckayJames Murphy Mckay More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003322.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The prognostic significance of lymph node (LN) positivity in renal cell carcinoma (RCC) is poorly understood. Currently, American Joint Committee on Cancer (AJCC) Stage III RCC includes both node-positive pN1 and node-negative pN0 disease. We hypothesize that (1) there is a threshold in number of pathologic positive LN (pLN) that distinguishes favorable from poor risk nodal disease, and (2) current categorization of pN1 can be subdivided into pN1 and pN2 based this threshold. We tested our hypothesis using the National Cancer Database (NCDB). METHODS: From 2004-2019, all RCC were queried in patients age ≥18. pN1 RCC with no synchronous metastasis were selected to minimize confounding from metastatic burden. Multivariable Cox regression tested association between number of pLN and all-cause mortality (ACM). Receiver Operator Characteristic (ROC) Curve analyses employing concordance probability method and analysis of regression coefficients evaluated performance of potential cut-points for pN2. Kaplan-Meier analyses (KMA) compared these thresholds against overall survival (OS) in non-metastatic Stage IV RCC. RESULTS: 29,388 patients were identified; 3910 (13.3%) had pN1. On Cox regression, increased number of pLN was associated with increased hazard of ACM (HR 1.19, p<0.001). Analysis of estimated regression coefficients identified potential threshold at ≥3 pLN. ROC mapping of thresholds ≥2 to ≥10 showed stable concordance probability 0.26-0.33, AUC=0.656. On KMA, when threshold was ≥3, 5-year OS was no longer significantly different from non- metastatic Stage IV RCC as illustrated by overlapping confidence intervals. We designated pN1 as 1-2 pLN, and pN2 as ≥3 pLN. 5-year OS for Stage III pN0 was 69.4% (95% CI 68.4-70.5), for Stage III pN1 was 41.4% (39.0-43.8), for Stage III pN2 was 31.8% (28.2-35.9%), and for non-metastatic Stage IV was 30.0% (28.2-32.0%). pN2 exhibited 38% greater hazard of ACM (HR 3.31, p<0.001) compared to pN1 (HR 2.39, p<0.001). CONCLUSIONS: These findings show that original pN1 RCC could be stratified to pN1 and pN2, with pN2 conferring poor prognosis comparable to non-metastatic Stage IV pN0 disease. Although validation studies are warranted, consideration should be given towards stratifying Stage III pN2 patients to a higher risk group. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e888 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luke Wang More articles by this author Florin Vaida More articles by this author Dhruv Puri More articles by this author Sohail Dhanji More articles by this author Franklin Liu More articles by this author Jonathan Afari More articles by this author Margaret Meagher More articles by this author Kevin Hakimi More articles by this author Mimi Nguyen More articles by this author Cesare Saitta More articles by this author Saeed Ghassemzadeh More articles by this author Aastha Shah More articles by this author Ryan Nasseri More articles by this author Juan Javier-Desloges More articles by this author James Murphy Mckay More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF downloadLoading ...

MP29-05 TREATMENT PATTERN AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) OF PATIENTS (PTS) WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) IN THE UNITED STATES (US)

You have accessJournal of UrologyCME1 Apr 2023MP29-05 TREATMENT PATTERN AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) OF PATIENTS (PTS) WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) IN THE UNITED STATES (US) Neal Shore, Lawrence Karsh, Daniel Shevrin, James Symanowski, Daniel Lin, Jeff Turner, David Russell, Yi Song, James Spalding, Filipa Negreiro, and David Penson Neal ShoreNeal Shore More articles by this author , Lawrence KarshLawrence Karsh More articles by this author , Daniel ShevrinDaniel Shevrin More articles by this author , James SymanowskiJames Symanowski More articles by this author , Daniel LinDaniel Lin More articles by this author , Jeff TurnerJeff Turner More articles by this author , David RussellDavid Russell More articles by this author , Yi SongYi Song More articles by this author , James SpaldingJames Spalding More articles by this author , Filipa NegreiroFilipa Negreiro More articles by this author , and David PensonDavid Penson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Therapeutic advances in the management of mCRPC have given clinicians multiple treatment options and the potential for sequencing therapeutic agents, increasing the complexity of treatment decisions. This study aims to describe the treatment patterns and HRQoL of pts with mCRPC in the US from 2015 to 2021. METHODS: This prospective, observational, multicentre study (TRUMPET) enrolled male adult pts who initiated treatment for mCRPC from 147 urology and oncology sites in the US. The data from routine clinic visits and periodic HRQoL questionnaires were collected from Mar 2015 to Apr 2021. The study outcomes assessed patterns of care and HRQoL outcomes (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and Brief Pain Inventory – Short Form [BPI-SF]) associated with mCRPC management. Descriptive analyses were used to evaluate results. RESULTS: Among the enrolled patients, the full analysis set included 832 patients with M1 mCRPC; the safety analysis set included 869 patients with M1 mCRPC. The median duration from initial diagnosis to baseline visit was 4.9 years, median initial prostate-specific antigen (PSA) level at diagnosis was 16.3 ng/mL, and mean (SD) Gleason score was 8.0 (1.18). Novel hormonal therapy (NHT) (enzalutamide and/or abiraterone) and immunotherapy were the most frequent initial treatments (Table). During the follow-up period, 43.8% (n=381) discontinued from the study before the first treatment switch, while 50.1% (n=435) switched treatment, with the majority of pts switching to NHT (n=280, 32.2%). At 1 year follow-up, cumulative first switches were 128 of 158 (81%) from immunotherapy to NHT, 41 of 88 (47%) switched from NHT to a different NHT, 11 of 17 (65%) switched from first-generation anti-androgens (AA) to NHT, 19 of 26 (73%) switched from chemotherapy to NHT, and 6 of 11 (55%) switched from radionuclide therapy to NHT. HRQoL measures showed similar trends (overlapping confidence intervals) of mean change from baseline across different first-line treatment options, irrespective of the initial treatment. CONCLUSIONS: NHT was the preferred first and second-line treatment option in pts with M1 mCRPC. HRQoL was similar regardless of initial treatment. Source of Funding: This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e382 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal Shore More articles by this author Lawrence Karsh More articles by this author Daniel Shevrin More articles by this author James Symanowski More articles by this author Daniel Lin More articles by this author Jeff Turner More articles by this author David Russell More articles by this author Yi Song More articles by this author James Spalding More articles by this author Filipa Negreiro More articles by this author David Penson More articles by this author Expand All Advertisement PDF downloadLoading ...