Prospective Validation Study Research Articles

Early detection of late-onset neonatal sepsis from noninvasive biosignals using deep learning: A multicenter prospective development and validation study

BackgroundNeonatal sepsis is responsible for significant morbidity and mortality worldwide. Its accurate and timely diagnosis is hindered by vague symptoms and the urgent necessity for early antibiotic intervention. The gold standard for diagnosing the condition is the identification of a pathogenic organism from normally sterile sites via laboratory testing. However, this method is resource-intensive and cannot be conducted continuously. ObjectiveThis study aimed to predict the onset of late-onset sepsis (LOS) with good diagnostic value as early as possible using non-invasive biosignal measurements from neonatal intensive care unit (NICU) monitors. MethodsIn this prospective multicenter study, we developed a multimodal machine learning algorithm based on a convolutional neural network (CNN) structure that uses the power spectral density (PSD) of recorded biosignals to predict the onset of LOS. This approach aimed to discern LOS-related pathogenic spectral signatures without labor-intensive manual artifact removal. ResultsThe model achieved an area under the receiver operating characteristic score of 0.810 (95 % CI 0.698–0.922) on the validation dataset. With an optimal operating point, LOS detection had 83 % sensitivity and 73 % specificity. The median early detection was 44 h before clinical suspicion. The results highlighted the additive importance of electrocardiogram and respiratory impedance (RESP) signals in improving predictive accuracy. According to a more detailed analysis, the predictive power arose from the morphology of the electrocardiogram’s R-wave and sudden changes in the RESP signal. ConclusionRaw biosignals from NICU monitors, in conjunction with PSD transformation, as input to the CNN, can provide state-of-the-art prediction performance for LOS without the need for artifact removal. To the knowledge of the authors, this is the first study to highlight the independent and additive predictive potential of electrocardiogram R-wave morphology and concurrent, sudden changes in the RESP waveform in predicting the onset of LOS using non-invasive biosignals.

Treatment of hepatocellular carcinoma according to multiparametric therapeutic hierarchy approach: a prospective multicenter validation study

Treatment of hepatocellular carcinoma according to multiparametric therapeutic hierarchy approach: a prospective multicenter validation study

Abstract WP82: The Dallas ED Screening Tool to Identify Stroke (DESTINY) Validation Study

Background: Screening is a valuable tool for triage, protocol activation, and resource allocation in emergency medicine, yet no tool is identified as superior in the prehospital or hospital setting. DESTINY is a screening tool developed as a single tool to screen for all stroke subtypes. Methods: This study is a phase II prospective 2-part adaptive design validation study of DESTINY in the ED during the early triage of suspected stroke patients from 05/01/2022 to 08/08/2022. CSTAT and VAN were embedded in the tool. DESTINY was incorporated into EHR and standardized workflow for nursing triage in ED. The NIHSS at presentation, primary diagnosis, and stroke subtypes were recorded. Symptomatic was defined as any new neurological deficit. During the blinded phase, only CSTAT score was provided for clinical decisions. Primary outcomes included predictability of DESTINY scores to identify acute symptomatic stroke and LVO. Secondary outcome included stroke performance measures. Score completion failures were retrospectively scored by a vascular neurologist provided with chief complaint and initial exam, blinded to final diagnosis and imaging. Results: During part 1, 284 patients were screened with DESTINY; 92 patients (32%) had score completion failures. Median: NIHSS at initial assessment 2 (mean 4.4; range 0 to 28); door to stroke scale start 6 minutes; door to stroke provider (thrombolytic eligible patients) 10 minutes; door to needle 62 minutes; door to puncture 94 minutes. Acute symptomatic stroke was recorded in 110 including LVO in 19. The DESTINY score with highest predictability for acute symptomatic stroke was > 1 (sensitivity 0.95 [95% CI 90.3-98.8], specificity 0.44 [95% CI 36.9-51.6]) and acute symptomatic LVO was > 3 or > 1 and at least one positive from questions 3 to 7 (sensitivity 1.0, specificity 0.63 [95% CI 56.8-68.5]). Conclusion: DESTINY at defined scores has promise as a single tool to identify patients with acute symptomatic stroke and LVO.

Are embryonic stem cell markers and ALDH1A1 relevant in the context of breast cancer estrogen positivity?

Embryonic pluripotency markers are recognized for their role in ER- BC aggressiveness, but their significance in ER+ BC remains unclear. This study aims to investigate the prevalence of expression of pluripotency markers in ER+ BC and their effect on survival and prognostic indicators. We analyzed data of ER+ BC patients from three large cancer datasets to assess the expression of three pluripotency markers (NANOG, SOX-2, and OCT4), and the stem cell marker ALDH1A1. Additionally, we investigated associations between gene expression, through mRNA-Seq analysis, and overall survival (OS). The prevalence of mutational variants within these genes was explored. Using immunohistochemistry (IHC), we examined the expression and associations with clinicopathologic prognostic indicators of the four markers in 81 ER+ BC patients. Through computational analysis, NANOG and ALDH1A1 genes were significantly upregulated in ER+ BC compared to ER- BC patients (p < 0.001), while POU5F1 (OCT4) was downregulated (p < 0.001). NANOG showed an adverse impact on OS whereas ALDH1A1 was associated with a highly significant improved survival in ER+ BC (p = 4.7e-6), except for the PR- and HER2+ subgroups. Copy number alterations (CNAs) ranged from 0.4% to 1.6% in these genes, with the highest rate detected in SOX2. In the IHC study, approximately one-third of tumors showed moderate to strong expression of each of the four markers, with 2-4 markers strongly co-expressed in 56.8% of cases. OCT-4 and ALDH1A1 showed a significant association with a high KI-67 index (p = 0.009 and 0.008, respectively), while SOX2 showed a significant association with perinodal fat invasion (p = 0.017). Pluripotency markers and ALDH1A1 are substantially expressed in ER+ BC tumors with different, yet significant, associations with prognostic and survival outcomes. This study suggests these markers as targets for prospective clinical validation studies of their prognostic value and their possible therapeutic roles.

Translation, cultural adaptation, and validation of the Standardized Cosmesis and Health Nasal Outcomes Survey in Japanese (J-SCHNOS)

Rhinoplasty is one of the most popular plastic surgery techniques. The evaluation of both functional and cosmetic aspects of rhinoplasty is essential for planning and assessing surgery results. The Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) is a validated questionnaire used to assess both functional and aesthetic symptoms in patients with nasal problems, and it has been translated into several languages. The purpose of this study was to translate, culturally adapt, and validate the SCHNOS in Japanese among patients undergoing rhinoplasty. This was a prospective validation study of the Japanese version of the SCHNOS (J-SCHNOS). The first phase involved translation and cross-cultural adaptation of the SCHNOS. The second phase included validation of the J-SCHNOS among native Japanese speakers. In total, 357 participants completed the final version of the J-SCHNOS (219 males and 138 females; mean age 43.4 years). The J-SCHNOS showed high internal consistency with excellent Cronbach's alpha values for both obstruction (SCHNOS-O) (0.96) and cosmetic (SCHNOS-C) (0.93) domains. The reproducibility was high, with an excellent intraclass correlation coefficient (ICC) >0.9 for all items. Exploratory factor analysis showed unidimensional structures in both the SCHNOS-O and the SCHNOS-C. The J-SCHNOS is a reliable and valid tool to assess the severity of nasal problems in patients undergoing rhinoplasty.

Feasibility of a Pediatric Acute Video Consultation Process Among Health Care Professionals in Primary Care in a Rural Setting: Protocol for a Prospective Validation Study.

For years, in Catalonia and in the rest of Spain, there has been a deficit and an unequal geographical distribution of health professionals specializing in pediatrics, especially in rural areas. Among the proposals to improve this situation is the promotion of the use of information and communication technologies (ICT) among users and professionals. Moreover, with the outbreak of COVID-19, the use of telehealth has become an essential tool, with an overall increase in non-face-to-face visits, including in primary care pediatrics. In this context, telemedicine, when used in primary care pediatrics, can be an effective means of improving families' access to medical care. Currently, in Catalonia, telemedicine involving patients and health professionals is used in pediatric primary care through telephone consultation and asynchronous teleconsultation (eConsulta). Video consultation is in practice not used, although it could have different applications. The aim of this study is to evaluate the feasibility of a video consultation process with physical examination in acute pediatric pathology in rural areas among primary care professionals. In addition, the level of satisfaction with these remote consultations will be assessed from the perspective of both the users and the health care professionals. We will conduct a prospective experimental study to analyze the possibility of using video consultation in pediatric acute care in primary care in central Catalonia (Spain). A minimum of 170 children aged between 0 and 14 years attending the primary care center (PCC) for acute illness for a period of 1 year will be included in the study. Initially, the telemetric visit, including a physical examination, will include a nurse at the patient and family's side and a pediatrician who will participate remotely. Subsequently, the pediatrician will visit the patient in person and the physical examination and diagnosis made during the remote visit will be compared with the physical examination and diagnosis of the face-to-face visit, which is considered the gold standard. Recruitment was planned to begin in the second half of 2023 and continue for at least 1 year. It is anticipated to be a good resource for a variety of acute pediatric conditions in primary care. The evaluation will focus on the feasibility of performing live remote visits and comparing their diagnostic accuracy with that of face-to-face visits. We believe that this study could provide evidence on the feasibility and diagnostic accuracy of video consultation in pediatric acute primary care in a rural setting, as well as on satisfaction with video consultations among both users and professionals. If proven useful in addressing the acute needs of children in a variety of situations, it could become a digital health tool that improves the overall pediatric primary care service in rural areas, for both families and professionals. PRR1-10.2196/52946.

Validation and Utility of a Novel Foot Offloading Device: Improving Pain and Function.

Foot pain is a common presentation, and management is generally geared toward pressure offloading. Although several pressure offloading devices exist on the market, the search for the optimal device is ongoing. We recently developed PopSole, an inexpensive, simple, balanced offloading insole focused on reducing targeted foot pain. We conducted a prospective validation study of patients with foot pain lasting longer than 6 months to assess the durability and efficacy of the device with follow-up scheduled at 2 weeks, 4 weeks, 2 months, and 3 months. Patient-reported outcomes were collected using multiple validated surveys. Fifteen patients were enrolled in this study. At 4 weeks, pain, function, and quality of life across all surveys showed statistically significant improvement. For the 6 patients with long-term outcomes (3 months), patients reported improvement in their pain, function, and quality of life across all surveys, which were significant in the Mayo survey (P = .018), the Manchester Foot Pain and Disability Index (P = .014), the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale (P = .032), the Foot and Ankle Ability Measure activities of daily living (P = .009), and the Pittsburgh foot survey (P = .01); the Foot and Ankle Ability Measure sports approached statistical significance (P = .058). The PopSole is a durable and effective device to relieve foot pain, improve function, and improve quality of life for up to 3 months of use.

Psychometric evaluation of a novel tool for assessing gestational diabetes and hypertension care: knowledge, attitudes, and practices of midwives and nurses.

While standardized assessment of knowledge, attitudes, and practices (KAP) related to gestational diabetes and hypertension is possible with a valid tool, existing research remains limited. This prospective validation study aimed to develop and validate a novel tool to assess the KAP of midwives and obstetric nurses. We included 125 midwives and obstetric nurses who routinely care for patients with gestational diabetes and hypertension. The tool demonstrated good internal consistency (Cronbach's alpha): knowledge (0.729, 95% CI, 0.654-0.776), attitude (0.756, 95% CI, 0.690-0.814), and practices (0.925, 95% CI, 0.905-0.943). Difficulty indices (d) ranged from 0.38 to 0.99 (knowledge), 0.41 to 0.99 (attitudes), and 0.41 to 0.93 (practices), indicating appropriate item difficulty. Discrimination indices (D) confirmed items could differentiate between respondents with low and high knowledge levels (D range: 0.02-0.77 for knowledge, 0.06-0.64 for attitudes, 0.20-0.84 for practices). The robust psychometric properties of this tool support its use in future research on KAP related to diabetes and gestational hypertension management in midwives and nurses. This instrument has the potential to be valuable in various settings, including baseline assessment before educational programs or evaluation of learning outcomes after interventions.

Conception and prospective multicentric validation of a Robotic Surgery Training Curriculum (RoSTraC) for surgical residents: from simulation via laboratory training to integration into the operation room

There is a lack of training curricula and educational concepts for robotic-assisted surgery (RAS). It remains unclear how surgical residents can be trained in this new technology and how robotics can be integrated into surgical residency training. The conception of a training curriculum for RAS addressing surgical residents resulted in a three-step training curriculum including multimodal learning contents: basics and simulation training of RAS (step 1), laboratory training on the institutional robotic system (step 2) and structured on-patient training in the operating room (step 3). For all three steps, learning content and video tutorials are provided via cloud-based access to allow self-contained training of the trainees. A prospective multicentric validation study was conducted including seven surgical residents. Transferability of acquired skills to a RAS procedure were analyzed using the GEARS score. All participants successfully completed RoSTraC within 1 year. Transferability of acquired RAS skills could be demonstrated using a RAS gastroenterostomy on a synthetic biological organ model. GEARS scores concerning this procedure improved significantly after completion of RoSTraC (17.1 (±5.8) vs. 23.1 (±4.9), p < 0.001). In step 3 of RoSTraC, all participants performed a median of 12 (range 5–21) RAS procedures on the console in the operation room. RoSTraC provides a highly standardized and comprehensive training curriculum for RAS for surgical residents. We could demonstrate that participating surgical residents acquired fundamental and advanced RAS skills. Finally, we could confirm that all surgical residents were successfully and safely embedded into the local RAS team.

P454 Systemic free thiols associate with clinical and biochemical disease activity in Inflammatory Bowel Disease: a prospective diagnostic validation study

Abstract Background In the pathophysiology of inflammatory bowel diseases (IBD), oxidative stress plays an important role. Lower levels of plasma free thiols (FT) reflect a higher oxidative stress burden and correlate with IBD disease activity. However, their clinical significance as biomarker for disease activity remains unclear. This study aimed to prospectively validate the utility of plasma FT levels as biomarker for clinical, biochemical, and endoscopic disease activity in patients with IBD. Methods In an ongoing prospective diagnostic trial aiming to include 100 IBD patients, we conducted an interim analysis of plasma FT levels in 52 patients with IBD (24 Crohn's disease [CD], 21 ulcerative colitis [UC], and 7 patients with undetermined IBD). Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and faecal calprotectin [fCal]). Endoscopic disease activity was quantified with the Mayo endoscopic subscore for UC and the Simple Endoscopic Score (SES-CD) for CD. Plasma FT levels were assessed for correlations with disease activity parameters using linear and logistic regressions models. Discriminative capacity of biomarkers was evaluated through calculating receiver operating characteristics (ROC) statistics. Results Plasma FT levels were significantly negatively correlated in clinical parameters, like HBI (r = -0.53, p &amp;lt; 0.05) (Fig. 1A). Other inflammatory biomarkers, like CRP, were also negatively correlated with plasma FT levels and were reduced in patients with active IBD (r = -0.43, p &amp;lt; 0.05) (Fig. 1B). Plasma FT levels accurately discriminated between CD patients with clinically quiescent (HBI &amp;lt; 5) and active disease (HBI ≥ 5) (AUC = 0.80, p = 0.02, Fig. 1C), better than fCal (AUC = 0.55, p = 0.83). Plasma FT were not significantly different for biochemically quiescent (CRP &amp;lt; 5 mg/l) and active (CRP ≥ 5mg/l) disease (AUC = 0.69, p = 0.20, Fig. 1D). Both Mayo and SES-CD scores, after adjusting for confounders, also exhibited a trend towards negative association with plasma FT levels (Fig. 1E). Figure 1 Conclusion Further completion of the trial will reveal whether systemic FT levels will reflect endoscopically observed disease activity, and this interim analysis shows strong correlations FT levels and parameters of clinically and biochemically active disease. Measuring systemic FTs in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity. Funding None

The construct validity, responsiveness, reliability and interpretability of the Recap of atopic eczema questionnaire (RECAP) in children.

The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). The measurement properties of RECAP have not yet been validated in caregivers of children with AD. To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP. A prospective validation study was conducted in children (aged < 12 years) with AD and their caregivers (in a Dutch tertiary hospital). At three timepoints (T0 = baseline; T1 = after 1-7 days; T2 = after 4-8 weeks) RECAP and multiple reference instruments were completed by caregivers of child patients. Single- and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Bands for perceived eczema control were proposed. The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC. A total of 231 children with AD and their caregivers participated. Of our a priori hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. A stronger correlation than hypothesized was found for all rejected hypotheses.Excellent reliability was found (ICCagreement = 0.94, 95% confidence interval 0.90-0.96). The SEMagreement was 1.9 points. The final banding was 0-1 (completely controlled), 2-7 (mostly controlled), 8-12 (moderately controlled), 13-18 (a little controlled) and 19-28 (not at all controlled). A cutoff point of ≥ 8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC values were 1.5 and 3.6 for the ROC and predictive modelling approaches, respectively. No floor or ceiling effects were observed. The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of ≥ 6 points can be regarded as a real and important change in children with AD.

Use of tumor-informed ctDNA across gastrointestinal cancers.

758 Background: In colorectal cancer (CRC), the use of ctDNA for the purpose of early recurrence detection and prognostication is established, and multiple studies are testing its utility for guiding adjuvant therapy decisions. Tumor informed testing can be performed in clinical situations where adequate tissue is available for next-generation sequencing (NGS). Increasingly, ctDNA testing is being used clinically for colorectal cancer patients and other gastrointestinal (GI) cancers when there is an appropriate clinical scenario and adequate tumor tissue is available for sequencing. Methods: We identified GI cancer patients treated at our institution where Signatera (Natera) testing was ordered and performed between 2020 – 2023. We included all patients for whom testing was ordered. Then, among patients with any result further analyzed results by disease type, stage, and results. We examined clinical rationale for testing and whether results informed subsequent decisions. Results: A total of 99 GI cancer patients for whom ctDNA testing was ordered were identified. 80 patients had at least 1 ctDNA result including 68 colorectal patients and 12 other GI cancers (anal, bile duct, esophagogastric, pancreatic, and small bowel). Among patients with measurable ctDNA, at the most recent testing timepoint 16 had levels that met criteria for positive detection, while 64 were undetectable. Most commonly, testing was ordered in stage II/III CRC patients for post-operative surveillance. Other clinical use scenarios included 1) surveillance/treatment monitoring in oligometastatic CRC, 2) surveillance in non-metastatic esophagogastric cancer, 3) treatment monitoring in MSI-H/immunotherapy sensitive GI cancers. For at least 18 patients, results were a factor in shared clinical decision making between patients and providers. Conclusions: We found ctDNA monitoring is most commonly used in the adjuvant setting for CRC patients which is best supported by existing studies. Our data demonstrates that tumor informed testing can be successful in other GI cancers for both surveillance and therapy monitoring. Given the broad and rapid adoption of this technology, there needs to be continued efforts for both prospective validation studies and retrospective real world studies to guide clinical practice.

Malnutrition prevalence according to GLIM and its feasibility in geriatric patients: a prospective cross-sectional study.

In 2019, the Global Leadership Initiative on Malnutrition (GLIM) suggested a 2-step diagnostic format for malnutrition including screening and diagnosis. Prospective validation and feasibility studies, using the complete set of the five GLIM criteria, are needed. The aims of this study were to determine the prevalence of malnutrition, and investigate how the prevalence varied with mode of screening. Furthermore, we assessed the feasibility of GLIM in geriatric patients. Consecutive patients from two acute geriatric wards were included. For screening risk of malnutrition, the Mini Nutritional Assessment-Short Form (MNA-SF) or Malnutrition Screening Tool (MST) were used. In accordance with GLIM, a combination of phenotypic and etiologic criteria were required for the diagnosis of malnutrition. Feasibility was determined based on % data completeness, and above 80% completeness was considered feasible. One hundred patients (mean age 82years, 58% women) were included. After screening with MNA-SF malnutrition was confirmed by GLIM in 51%, as compared with 35% after screening with MST (p = 0.039). Corresponding prevalence was 58% with no prior screening. Using hand grip strength as a supportive measure for reduced muscle mass, 69% of the patients were malnourished. Feasibility varied between 70 and 100% for the different GLIM criteria, with calf circumference as a proxy for reduced muscle mass having the lowest feasibility. In acute geriatric patients, the prevalence of malnutrition according to GLIM varied depending on the screening tool used. In this setting, GLIM appears feasible, besides for the criterion of reduced muscle mass.

Transparency in Artificial Intelligence Reporting in Ophthalmology-A Scoping Review

This scoping review summarizes artificial intelligence (AI) reporting in ophthalmology literature in respect to model development and validation. We characterize the state of transparency in reporting of studies prospectively validating models for disease classification. Understanding what elements authors currently describe regarding their AI models may aid in the future standardization of reporting. This review highlights the need for transparency to facilitate the critical appraisal of models prior to clinical implementation, to minimize bias and inappropriate use. Transparent reporting can improve effective and equitable use in clinical settings. Eligible articles (as of January 2022) from PubMed, Embase, Web of Science, and CINAHL were independently screened by 2 reviewers. All observational and clinical trial studies evaluating the performance of an AI model for disease classification of ophthalmic conditions were included. Studies were evaluated for reporting of parameters derived from reporting guidelines (CONSORT-AI, MI-CLAIM) and our previously published editorial on model cards. The reporting of these factors, which included basic model and dataset details (source, demographics), and prospective validation outcomes, were summarized. Thirty-seven prospective validation studies were included in the scoping review. Eleven additional associated training and/or retrospective validation studies were included if this information could not be determined from the primary articles. These 37 studies validated 27 unique AI models; multiple studies evaluated the same algorithms (EyeArt, IDx-DR, and Medios AI). Details of model development were variably reported; 18 of 27 models described training dataset annotation and 10 of 27 studies reported training data distribution. Demographic information of training data was rarely reported; 7 of the 27 unique models reported age and gender and only 2 reported race and/or ethnicity. At the level of prospective clinical validation, age and gender of populations was more consistently reported (29 and 28 of 37 studies, respectively), but only 9 studies reported race and/or ethnicity data. Scope of use was difficult to discern for the majority of models. Fifteen studies did not state or imply primary users. Our scoping review demonstrates variable reporting of information related to both model development and validation. The intention of our study was not to assess the quality of the factors we examined, but to characterize what information is, and is not, regularly reported. Our results suggest the need for greater transparency in the reporting of information necessary to determine the appropriateness and fairness of these tools prior to clinical use. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study

IntroductionNon-alcoholic fatty liver disease (NAFLD) affects approximately one in four individuals and its prevalence continues to rise. The advanced stages of NAFLD with significant liver fibrosis are associated with adverse...

Pulmonary embolism risk stratification: external validation of the 4-level Clinical Pretest Probability Score (4PEPS)

BackgroundThe 4-level clinical pretest probability score (4PEPS) was recently introduced as a clinical decision rule for the diagnosis of pulmonary embolism (PE). Based on the score, patients are classified into clinical pretest probability categories (c-PTP). The “very low” category aims at excluding PE without further testing; “low” and “moderate” categories require D-dimer testing with specific thresholds, while patients with a “high” pretest directly proceed to imaging. ObjectivesTo provide further external validation of the 4PEPS model. MethodsThe 4PEPS was applied to a previously collected prospective database of 756 patients with clinically suspected PE enrolled from European emergency departments in 2002 to 2003. The safety threshold for the failure rate in our study was calculated at 1.95% based on a 26% prevalence of PE in our study, as per the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee guidance. ResultsPatients were classified as follows: 90 (12%) in the very low c-PTP group, of whom 5 (5.6%; 95% CI, 2.4%-12.4%) had PE; 363 (49%) in the low c-PTP group, of whom 34 had PE (9.4%); 246 (34%) in the moderate c-PTP group, of whom 124 (50%) had PE; and 35 (5%) in the high c-PTP group of whom 30 (86%) had PE. Overall, the failure rate of the 4PEPS was 9/734 (1.2%; 95% CI, 0.59%-2.23%) Overall, 9 out of 734 patients (1.2%; 95% CI, 0.59%-2.23%) were diagnosed with PE despite a negative 4PEPS rule; 5 (5.6%) from the very low c-PTP group, 3 (1.4%) in the low c-PTP group, and 1 (3.2%) in the moderate c-PTP group. ConclusionWe provide external validation data of the 4PEPS. In this high-prevalence cohort (26% prevalence), PE prevalence in the very low-risk group was higher than expected. A prospective validation study is needed before implementing the 4PEPS model in routine clinical practice.

Assessing insomnia after stroke: a diagnostic validation of the Sleep Condition Indicator in self-reported stroke survivors.

Insomnia is common after stroke and is associated with poorer recovery and greater risk of subsequent strokes. Yet, no insomnia measures have been validated in English-speaking individuals affected by stroke. This prospective diagnostic validation study investigated the discriminatory validity and optimal diagnostic cut-off of the Sleep Condition Indicator when screening for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) insomnia disorder post-stroke. A convenience sample of 180 (60.0% women, mean age=49.61 ± 12.41 years) community-based, adult (≥18 years) self-reported stroke survivors completed an online questionnaire. Diagnosis of DSM-5 insomnia disorder was based on analysis of a detailed sleep history questionnaire. Statistical analyses explored discriminant validity, convergent validity, relationships with demographic and mood variables, and internal consistency. Receiver operating characteristic curves were plotted to assess diagnostic accuracy. Data from the sleep history questionnaire suggested that 75 participants (41.67%) met criteria for DSM-5 insomnia disorder, 33 (18.33%) exhibited symptoms of insomnia but did not meet diagnostic criteria, and 72 (40.0%) had no insomnia symptoms at the time of assessment. The Sleep Condition Indicator (SCI) demonstrated 'excellent' diagnostic accuracy in the detection of insomnia post-stroke, with an area under the curve of 0.86 (95% CI (0.81, 0.91)). The optimal cut-off was determined as being ≤13, yielding a sensitivity of 88.0% and a specificity of 71.43%. The findings of this study demonstrate the SCI to be a valid and reliable method with which to diagnose DSM-5 insomnia disorder and symptoms post-stroke. However, a lower threshold than is used in the general population may be necessary after stroke.

Algorithm Development and Early Performance Evaluation of a Next-Generation Multitarget Stool DNA Screening Test for Colorectal Cancer

Background and AimsThe multitarget stool DNA (mt-sDNA) assay is a non-invasive average-risk colorectal cancer (CRC) screening test. A new biomarker panel was developed for a next-generation test to improve specificity while maintaining/increasing sensitivity. We aimed first to establish an algorithm and cutoff for the next-generation mt-sDNA test and then to validate it using archived samples from the pivotal DeeP-C study (NCT01397747) of the first-generation test. MethodsAlgorithm development and cross-validation included 3011 samples from 2 specimen collection studies (NCT03821948, NCT03789162). The algorithm and cutoff were locked before validation. Validation test set samples included 57 CRC, 583 advanced precancerous lesions (APLs), and 7022 samples negative for CRC or APLs from the DeeP-C study, which prospectively enrolled average-risk, asymptomatic adults aged 50 to 84 years before screening colonoscopy. Next-generation biomarkers included methylated DNA markers LASS4, LRRC4, PPP2R5C, and ZDHHC1 (reference marker), and fecal hemoglobin. Primary validation endpoints were CRC sensitivity and specificity for the absence of advanced neoplasia. Secondary endpoints included APL sensitivity and specificity for non-neoplastic findings or negative colonoscopy. ResultsCross-validation and best-fit results from algorithm development closely matched, confirming algorithm reliability and reproducibility. For the test set, next-generation mt-sDNA test sensitivity was 93.0% (95% CI, 83.0%-98.1%) for CRC and 48.4% (95% CI, 44.2%-52.5%) for APLs. Specificity was 88.5% (95% CI, 87.7%-89.2%) for the absence of advanced neoplasia and 90.4% (95% CI, 89.5%-91.2%) for the combination of non-neoplastic findings or negative colonoscopy. ConclusionsBased on archived samples, the next-generation mt-sDNA test demonstrated promising CRC screening performance characteristics that will be further assessed in a prospective clinical validation study (BLUE-C; NCT04144738).

Role of C-Reactive Proteins at Early Gestational Age in Predicting Pre-Eclampsia in Pregnant Females

Background: Pre-eclampsia remains a significant concern in obstetrics due to its potential complications for both mother and fetus. Early detection of pre-eclampsia (PE0 is crucial for timely intervention and management. C-Reactive Protein (CRP), an inflammatory marker, has shown promise as a potential predictor of pre-eclampsia when assessed during early gestational age. Objective: To evaluate the diagnostic accuracy of raised serum CRP levels in early gestation to predict the risk of pre-eclampsia in pregnant females. Study Design: Prospective validation Study. Settings: Outdoor Department of obstetrics and gynecology, Lady Atchison Hospital Lahore. Duration: 02-September 2021 to 01-March-2022. Methods: A total of 130 pregnant females having gestational age 16 to 20 weeks and presenting in the hospital for regular antenatal visits were included. A five ml venous blood sample was drawn and was sent to the central hospital laboratory for determination of CRP levels from each case. Patients having CRP ≥5.0 mg/L were labelled as high risk of pre-eclampsia. All patients followed till delivery to determine the development of pre-eclampsia. Results: The mean age of the patients was found to be 28.16±4.74 years, with a mean BMI of 26.27±5.05 kg/m². Among the 130 patients, 12 (9.23%) were identified as having elevated CRP levels, while the remaining 118 (90.77%) showed normal CRP levels. Additionally, pre-eclampsia was diagnosed in 11 (8.46%) of the patients. Evaluation of the diagnostic accuracy of CRP levels revealed a sensitivity of 81.8% and specificity of 97.5%. The positive predictive value (PPV) was calculated at 75%, while the negative predictive value (NPV) stood at 98.3%. Conclusion: The study observed that elevated CRP levels in early pregnancy serve as a significant predictor of pre-eclampsia, with sensitivity of 81.8%, indicating its ability to correctly identify those with pre-eclampsia, while the specificity was 97.5%, suggesting its accuracy in ruling out those without the condition.