International Validation Study Research Articles

Artificial Intelligence-based Segmentation of Residual Pancreatic Cancer in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2): International Improvement and Validation Study.

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest were annotated and classified as cancer, non-neoplastic pancreatic ducts, and others. A U-Net model was trained to detect RPC. Validation consisted of by-scanner internal-external cross-validation. Overall, 528 unique hematoxylin and eosin (H & E) slides from 528 patients were included. In the individual Philips, Hamamatsu, 3DHistech, and Leica scanner cross-validations, mean F1 scores of 0.81 (95% CI, 0.77-0.84), 0.80 (0.78-0.83), 0.76 (0.65-0.78), and 0.71 (0.65-0.78) were achieved, respectively. In the meta-analysis of the cross-validations, the mean F1 score was 0.78 (0.71-0.84). A final model was trained on the entire data set. This ISGPP model is the first segmentation model using artificial intelligence techniques to objectively quantify RPC following NAT. The internally-externally cross-validated model in this study demonstrated robust performance in detecting RPC in specimens. The ISGPP model, now made publically available, enables automated RPC segmentation and forms the basis for objective NAT response evaluation in pancreatic cancer.

Comparison of the ASAS Health Index in patients classified as radiographic axial spondyloarthritis (axSpA) or non-radiographic axSpA in the ASAS Health Index international validation study

ObjectivesTo determine if there were differences in the Assessment of SpondyloArthritis international Society Health Index (ASAS HI) scores between patients classified as radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axSpA (nr-axSpA),...

Association of laboratory test results with the bleeding history in patients with inherited platelet function disorders (the Bleeding Assesment Tool - LABoratory tests substudy): communication from the Platelet Physiology ISTH-SSC

BackgroundIn hemophilia and von Willebrand disease, the degree of alteration of laboratory assays correlates with bleeding manifestations. Few studies have assessed the predictive value for bleeding of laboratory assays in patients with inherited platelet function disorders (IPFDs). ObjectivesTo assess whether there is an association between platelet function assay results and bleeding history, as evaluated by the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT). MethodsCenters participating in the international ISTH-BAT validation study were asked to provide results of the diagnostic assays employed for the patients they enrolled, and the association with the individual patients’ bleeding score (BS) was assessed. ResultsSixty-eight patients with 14 different IPFDs were included. Maximal amplitude of platelet aggregation was significantly lower in patients with a pathologic BS and correlated inversely with the BS, a finding largely driven by the subgroup of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency; after their exclusion, TRAP-induced aggregation remained significantly lower in patients with a pathologic BS. Bleeding time was significantly more prolonged in patients with a high BS than in those with a normal BS (27.1 ± 6.2 minutes vs 15.1 ± 10.6 minutes; P < .01). Reduced α-granule content was significantly more common among patients with a pathologic BS than among those with a normal BS (80% vs 20%; P < .05). Receiver operating characteristic curve analysis revealed a significant discriminative ability of all the aforementioned tests for pathologic BS (P < .001), also after exclusion of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency. ConclusionThis study shows that altered platelet laboratory assay results are associated with an abnormal ISTH-BAT BS in IPFD.

Multianalyte analysis of volatile compounds in virgin olive oils using SPME‐GC with FID or MS detection: results of an international interlaboratory validation

AbstractThe organoleptic assessment (Panel test) is the only procedure within the official methods for determining the quality of virgin olive oils that involves an expert panel. There is an urgent need for analytical methodology that can reliably measure volatile compounds in virgin olive oils that is capable of supporting and anticipating the official Panel test. For this reason, a new method based on solid‐phase microextraction–gas chromatography with the choice of two possible detectors (FID or MS) was subjected to a large international interlaboratory validation study. The study involved a two‐stage process: first, a pretrial phase in which 7 participants were exposed to the method for the first time to identify any initial problems with the methodology; then, a formal validation stage (trial proper), which involved 20 laboratories from Europe, USA, Japan and China. The performance of the different detectors was investigated. While both methods have advantages, the method using FID provided better results for 11 compounds, in terms of reproducibility, compared to MS. This information will allow to implement the method with accurate information of the method performance depending on the detector used.Practical applications: This study provides information from an interlaboratory validation of a method for measuring volatile compounds in virgin olive oils conducted with laboratories (from industry and academia) working in the olive oil sector. The information on the expected analytical errors in the determination of each volatile compound is necessary to apply this method for supporting the official Panel test (sensory analysis). The SPME‐GC‐MS/FID methods proposed in this work can be used for the internal quality control of a company/distributor/quality control laboratory and could also be used in cases of difficult/contradictory organoleptic assessment, or to confirm results from sensory panels in cases of disputes/disagreement (Reg. EU 2022/2105).

International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy.

No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.

An international multi-institutional validation study of the algorithm for prostate cancer detection and Gleason grading

Pathologic examination of prostate biopsies is time consuming due to the large number of slides per case. In this retrospective study, we validate a deep learning-based classifier for prostate cancer (PCA) detection and Gleason grading (AI tool) in biopsy samples. Five external cohorts of patients with multifocal prostate biopsy were analyzed from high-volume pathology institutes. A total of 5922 H&E sections representing 7473 biopsy cores from 423 patient cases (digitized using three scanners) were assessed concerning tumor detection. Two tumor-bearing datasets (core n = 227 and 159) were graded by an international group of pathologists including expert urologic pathologists (n = 11) to validate the Gleason grading classifier. The sensitivity, specificity, and NPV for the detection of tumor-bearing biopsies was in a range of 0.971–1.000, 0.875–0.976, and 0.988–1.000, respectively, across the different test cohorts. In several biopsy slides tumor tissue was correctly detected by the AI tool that was initially missed by pathologists. Most false positive misclassifications represented lesions suspicious for carcinoma or cancer mimickers. The quadratically weighted kappa levels for Gleason grading agreement for single pathologists was 0.62–0.80 (0.77 for AI tool) and 0.64–0.76 (0.72 for AI tool) for the two grading datasets, respectively. In cases where consensus for grading was reached among pathologists, kappa levels for AI tool were 0.903 and 0.855. The PCA detection classifier showed high accuracy for PCA detection in biopsy cases during external validation, independent of the institute and scanner used. High levels of agreement for Gleason grading were indistinguishable between experienced genitourinary pathologists and the AI tool.

Construct validity and reliability of the Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) questionnaire.

Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of RP in SSc. An international multicentre study validation study of the 27-item Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1 week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning. A total of 420 SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648-0.727, P < 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258-0.504, P < 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427-0.575, P < 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (P < 0.05 for all comparisons). There was excellent repeatability at 1 week among patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, P < 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77, respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53, 7.81, P = 0.029) was estimated. ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP.

The Skeletal Oncology Research Group Machine Learning Algorithm (SORG-MLA) for predicting prolonged postoperative opioid prescription after total knee arthroplasty: an international validation study using 3,495 patients from a Taiwanese cohort

BackgroundPreoperative prediction of prolonged postoperative opioid use (PPOU) after total knee arthroplasty (TKA) could identify high-risk patients for increased surveillance. The Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) has been tested internally while lacking external support to assess its generalizability. The aims of this study were to externally validate this algorithm in an Asian cohort and to identify other potential independent factors for PPOU.MethodsIn a tertiary center in Taiwan, 3,495 patients receiving TKA from 2010–2018 were included. Baseline characteristics were compared between the external validation cohort and the original developmental cohorts. Discrimination (area under receiver operating characteristic curve [AUROC] and precision-recall curve [AUPRC]), calibration, overall performance (Brier score), and decision curve analysis (DCA) were applied to assess the model performance. A multivariable logistic regression was used to evaluate other potential prognostic factors.ResultsThere were notable differences in baseline characteristics between the validation and the development cohort. Despite these variations, the SORG-MLA (https://sorg-apps.shinyapps.io/tjaopioid/) remained its good discriminatory ability (AUROC, 0.75; AUPRC, 0.34) and good overall performance (Brier score, 0.029; null model Brier score, 0.032). The algorithm could bring clinical benefit in DCA while somewhat overestimating the probability of prolonged opioid use. Preoperative acetaminophen use was an independent factor to predict PPOU (odds ratio, 2.05).ConclusionsThe SORG-MLA retained its discriminatory ability and good overall performance despite the different pharmaceutical regulations. The algorithm could be used to identify high-risk patients and tailor personalized prevention policy.

A protocol of an international validation study to assess the clinical accuracy of the eDIS-ICU delirium screening tool

BackgroundDelirium is a common, yet underdiagnosed neuropsychiatric complication of intensive care unit (ICU) admission, associated with significant mortality and morbidity. Delirium can be difficult to diagnose, with gold standard assessments by a trained specialist being impractical and rarely performed. To address this, various tools have been developed, enabling bedside clinicians to assess for delirium efficiently and accurately. However, the performance of these tools varies depending on factors including the assessor's training. To address the shortcomings of current tools, electronic tools have been developed. Aims and objectivesThe aims of this validation study are to assess the feasibility, acceptability, and generalisability of a recently developed and pilot-tested electronic delirium screening tool (eDIS-ICU) and compare diagnostic concordance, sensitivity, and specificity between eDIS-ICU, Confusion Assessment Method for the ICU (CAM-ICU), and the Diagnostic and Statistical Manual of Mental Disorders – 5th edition (DSM-V) gold standard in diverse ICU settings. MethodsSeven hundred participants will be recruited across five sites in three countries. Participants will complete three assessments (eDIS-ICU, CAM-ICU, and DSM-V) twice within one 24-h period. At each time point, assessments will be completed within one hour. Assessments will be administered by three different people at any given time point, with the assessment order and assessor for eDIS-ICU and CAM-ICU randomly allocated. Assessors will be blinded to previous and concurrent assessment results. ResultsThe primary outcome is comparing diagnostic sensitivity of eDIS-ICU and CAM-ICU against the DSM-V. Relevance to clinical practiceThis protocol describes a definitive validation study of an electronic diagnostic tool to assess for delirium in the ICU. Delirium remains a common and difficult challenge in the ICU and is linked with multiple neurocognitive sequelae. Various challenges to routine assessment mean many cases are still unrecognised or misdiagnosed. An improved ability for bedside clinicians to screen for delirium accurately and efficiently will support earlier diagnosis, identification of underlying cause(s) and timely treatments, and ultimately improved patient outcomes. Clinical trial registration numberThis study was prospectively registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) on 8th February 2022 (ACTRN12622000220763).

Development and multicenter international validation of a diagnostic tool to differentiate between pemphigoid gestationis and polymorphic eruption of pregnancy

Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) may be similar morphologically but confer different maternal and fetal risks. Direct immunofluorescence is the gold standard test used to differentiate between the 2 diagnoses but is not always available. To develop and validate a clinical scoring system to differentiate PG from PEP. After developing a scoring system based on differentiating clinical factors reported in existing literature, we tested its diagnostic accuracy in a retrospective international multicenter validation study in collaboration with the European Academy of Dermatology and Venereology's Skin Diseases in Pregnancy Taskforce. Nineteen pregnancies (16 patients) affected by PG and 39 pregnancies (39 patients) affected by PEP met inclusion criteria. PG had a mean score of 4.6 (SD, 2.5) and PEP had a mean score of -0.3 (SD, 2.0). The area under the curve was 0.93 (95% CI, 0.86-1.00). Univariate analysis revealed that almost all criteria used in the scoring system were significantly different between the groups (P<.05), except for skip pregnancy and multiple gestations, which were then removed from the final scoring system. Small retrospective study. The Pregnancy Dermatoses Clinical Scoring System may be useful to differentiate PG from PEP in resource-limited settings.

Screening tools for predicting mortality of adults with suspected sepsis: an international sepsis cohort validation study

ObjectivesWe evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana.DesignProspective cohort studies.Setting and participantsFrom 2014 to 2021, participants with two...

21TiP Molecular alterations predictive of outcome in early staged cervical cancer: A translational investigation in the international validation study of sentinel node biopsy in early cervical cancer SENTICOL III

Cervical cancer remains the second cause of cancer death in women worldwide. Despite of good histological and clinical features, some patients relapse after the treatment of early stage cervical cancer. Recent studies identified correlation between some genetic alterations and poor prognosis in advanced-staged cervical cancer. Yet, the literature remains scarce about molecular alterations and outcome correlation in early stage cervical cancer. Our translational study investigate recurrent molecular alterations predictive of outcome in early stage cervical cancer. We included the first 100 patients randomized in the Senticol III trial. This large multicentric, prospective, randomized, and international “validation study” tries to validate sentinel node biopsy as nodal staging of early cervical cancers (stage Ia – IIa1). Cervical tumor slides with contributive FFPE sample are analyzed and stratified based on well-established histological criteria (SEDLIS criteria). The immune microenvironment characteristics including TIL’s infiltration and PDL1 expression. PDL1 expression is assessed by IHC using the 22C3 antibody and quantified using CPS score. We made HPV detection and typing by PCR of the tumor samples. We performed DNA and RNA extractions from the FFPE tumor specimens. Using the dedicated gene panel developed by our team, we analyzed 571 genes commonly altered in cancer. We performed high throughput RNA sequencing to establish the gene expression profile of each tumor and its associated stroma. The genomic and transcriptomic analysis assessed the tumor mutational load, the most frequently altered genes and their expression. The biostatistical analyses will correlate molecular alterations, histopathological and clinical classical features, with patient outcome. The different parameters will be first analyzed independently (univariate analysis) and then in a multiparametric manner (logistic regression). NCT03386734. Fabrice Lecuru, MD PhD.

Autosegmentation of Residual Pancreatic Cancer Burden in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2): International Improvement and Validation Study

Autosegmentation of Residual Pancreatic Cancer Burden in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2): International Improvement and Validation Study

Raising the standards of patient-centered outcomes research in myelodysplastic syndromes: Clinical utility and validation of the subscales of the QUALMS from the MDS-RIGHT project.

Clinical decision-making for patients with myelodysplastic syndromes (MDS) is challenging, and both disease and treatment effects heavily impact health-related quality of life (HRQoL) of these patients. Therefore, disease-specific HRQoL measures can be critical to harness the patient voice in MDS research. We report a prospective international validation study of the Quality of Life in Myelodysplasia Scale (QUALMS) with a main focus on providing information on the psychometric characteristics of its three subscales: physical burden (QUALMS-P), emotional burden (QUALMS-E), and benefit finding (QUALMS-BF). The analysis is based on patients enrolled from three European countries and Israel, participating to the MDS-RIGHT Project. The scale structure and psychometric properties of the QUALMS were assessed. Overall, 270 patients with a median age of 74 years were analyzed and the majority of them (60.3%) had a low MDS-Comorbidity Index score. Results of the confirmatory factor analysis supported the underlying scale structure of the QUALMS, which, in addition to a total score, includes three subscales: QUALMS-P, QUALMS-E, and the QUALMS-BF. The QUALMS-P exhibited the highest Cronbach's alpha coefficients. Discriminant validity analysis indicated good results with the QUALMS-P and QUALMS-E distinguishing between patients with different performance status, comorbidity, anemia, and transfusion dependency status. No floor and ceiling effects were observed. Responsiveness to change analysis supported the validity of the measure. Patients with a hemoglobin (Hb) level of <11 g/dL at study entry, who subsequently showed an improvement in their Hb levels, also reported a mean score change of 9 and 8 points (scales ranging between 0 and 100) in the expected direction of the QUALMS-E and QUALMS-P, respectively. Our study provides additional validation data on the QUALMS from the international MDS-RIGHT Project. The use of this disease-specific HRQoL measure may contribute to raise quality standards of patient-centered outcomes research in MDS.

An international validation study of the interleukin-2 luciferase leukocyte toxicity test (IL-2 Luc LTT) to evaluate potential immunosuppressive chemicals and its performance after use with the interleukin-2 luciferase assay (IL-2 Luc assay)

We previously reported that the IL-2 Luc LTT can detect immunosuppressive effects of drugs that are attributed to their antimitotic activity. Here, we report an official validation study of the IL-2 Luc LTT. In the Phase I study that evaluated five coded chemicals, the within-laboratory reproducibility of three independent laboratories was 100.0%. In the combined results of the Phase I and II studies that evaluated 20 coded chemicals, the between-laboratory reproducibility was 92.0%. When compared with the reference data based on the previously-reported immunotoxicological information, the predictivity of the combined Phase I and II studies was 76.0% for Lab A and 72.0% for Labs B and C. In contrast, in the study in which the lead laboratory examined 37 non-pharmaceutical chemicals, the predictivity of the IL-2 Luc LTT and the IL-2 Luc assay was 48.6% and 64.9%, respectively, whereas that of the combined assays was 74.3%. It is clear that an integrated approach combining multiple assays is necessary for the development of in vitro immunosuppression testing. These data suggest that the IL-2 Luc LTT alone is not sufficient as a component of the integrated approach, but the combination of the IL-2 Luc assay and IL-2 Luc LTT is promising.

The Impact of Perceived Upper Extremity Severity and Prior Surgery on Patient-Reported Outcomes.

Background: The recently validated Hand Questionnaire (HAND-Q) is a multifaceted patient-reported outcome measure (PROM) for hand/upper extremity (UE) pathology and treatment. Here, we conduct a pilot study utilising data collected as a participating site for the Phase II HAND-Q Pilot Multicenter International Validation Study. We hypothesised that self-reported hand functionality, symptom/disease severity, hand appearance, emotional dissatisfaction and treatment satisfaction would be worse in patients who perceived their disease severity to be more severe but would not differ between patients based on prior surgical history. Methods: Patients were prospectively enrolled for HAND-Q participation from September 2018 to August 2019. Patients were included in this analysis if they responded to the following scales of HAND-Q: Hand Functionality Satisfaction, Symptom Severity, Hand Appearance Satisfaction, Emotional Dissatisfaction and Treatment Satisfaction. Composite scores (CS) were created for each section. Surgical versus non-surgical CS and mild versus moderate/severe CS were compared with t-tests. Bi-variate comparisons of responses were performed between surgical and non-surgical groups, and between mild and moderate/severe groups. Results: HAND-Q individual question analysis revealed significant differences in functionality and symptom severity for patients with prior surgery (p < 0.047). CS analysis confirmed greater overall impairment in surgical patients, but no overall impact on symptom severity. Regarding disease severity HAND-Q individual question analysis, moderate/severe patients reported worse outcomes for specific aesthetic qualities and symptoms for almost all items (p < 0.05). CS analysis revealed significantly worse overall hand appearance satisfaction, hand functionality, emotional satisfaction and symptom severity for patients with moderate/severe hand conditions. Conclusions: HAND-Q revealed worsened outcomes for UE patients with self-reported moderate/severe conditions or previous surgical history. Understanding how previous surgery and disease severity may impact clinical outcomes is important for crafting appropriate treatment. Level of Evidence: Level II (Prognostic Study).

What do we need to know about anatomy in gynaecology? An international validation study

ObjectiveInternational validation of the Dutch Delphi study about which anatomical structures should be taught to ensure safe and competent practice among general gynaecologists. Study designValidation study with gynaecologists and trainees in gynaecology from academic, non-academic teaching and non-academic, non-teaching hospitals worldwide.The relevance of 123 items included in the Dutch Delphi study was scored on a Likert scale between 1 (not relevant) and 5 (highly relevant). Consensus was defined when ≥70 % of the panellist scored the item as relevant or very relevant and the average rating was ≥4. ResultsA total of 192 gynaecologists and trainees from seven countries (Belgium, Germany, Norway, Oceania, Sweden, United Kingdom and United States) completed the questionnaire. Of the 123 structures, 72 (58.5%) were internationally relevant. When the 72 relevant structures from the international Delphi study were compared with the 86 relevant structures from the Dutch Delphi study, 70 (81.4%) structures matched. ConclusionsThis study identified 70 anatomical structures that should be taught for safe and competent practice of general gynaecologists based on national and international validation. The results of our study identify the learning needs (i.e., the content) for an international anatomy curriculum. The development of the curriculum (i.e., the form) can be determined by each country and used to standardize and guide postgraduate training in gynaecology. This is an important step in the era of international teaching and training.

PL02.4.A International validation study of an EORTC instrument measuring instrumental activities of daily living (IADL) in patients with brain tumours: EORTC IADL-BN32

Abstract Background Brain tumour patients often have neurocognitive deficits which can result in problems with activities in daily living that are cognitively complex. Currently, no valid and reliable brain tumour-specific instrument to measure these instrumental activities of daily living (IADL) is available, but such an instrument is being developed. This study aimed to validate the EORTC IADL-BN32 questionnaire, comprising five multi-item and two single item scales, in a large set of international brain tumour patients. Material and Methods This international study was conducted in 10 countries worldwide. Primary and metastatic brain tumour patients and their proxies were requested to complete the EORTC IADL-BN32 and a subjective cognitive questionnaire (MOS COG-R) at multiple time points. Several psychometric properties were evaluated with baseline data, including the structural validity (bi-factor confirmatory factor analysis [CFA]), reliability (internal consistency), construct validity (known groups comparisons) and patient-proxy congruency (intra-class correlation coefficients [ICC], Spearman's correlation). Results At baseline, 326 patients ( 30% low-grade glioma, 37% high-grade glioma (HGG) and 33% brain metastases) and 311 proxies completed the EORTC IADL-BN32. The bi-factor CFA was found to have a satisfactory model fit (CFI=0.92 and TLI=0.90), and other parameters indicated a good fit (RMSEA=0.08 and SRMR=0.05), thereby validating the preliminary scale structure, but also an IADL sum score. The multi-item scales showed good (0.9&amp;gt;α≥0.8) to excellent (α≥0.9) internal consistency (range α=0.86-0.97). Known groups comparisons analyses regarding patient’s cognitive status (indications vs. no cognitive impairment), subjective cognitive complaints (MOS COG-R ≤30 vs. &amp;gt;30), basic ADL (Barthel Index &amp;lt;100 vs. 100) and performance status (KPS &amp;lt;70 vs. ≥70) showed significant differences on all IADL outcome measures in line with a priori defined hypotheses. On a group level, patient and proxy ratings had moderate to strong correlations, however, proxies tended to report more problems on all scales. The ICCs showed moderate to good congruency between patients and proxies (range ICC: 0.63-0.81). Conclusion The evaluated psychometric properties support the current scale structure of the EORTC IADL-BN32. Additional psychometric properties with longitudinal data are needed, such as test-retest reliability and responsiveness, to further validate the EORTC-IADL BN32 questionnaire.

Communication support needs assessment in dementia (CoSNAT-D): An international content validation study.

The decline of language and communication abilities is common among people living with dementia and impacts on many areas of everyday life, including active participation in social activities and decision-making. Despite a growing body of supporting evidence for approaches that address language and communication decline in dementia, the concept of communication rehabilitation is largely neglected in this population. This paper reports on the content validation of a novel tool, the Communication Support Needs Assessment Tool for Dementia (CoSNAT-D). The tool has been developed to assist in the initial identification of communication difficulties and related support needs of people living with dementia. Importantly, the CoSNAT-D is the only available tool that takes a three-way informed approach, considering the view of the person living with dementia, their carer and an administering healthcare professional. Content validity was established between September and December 2018 using a modified Delphi approach. An international expert panel rated 32 items of a face-validated item pool regarding their importance and relevance through an iterative feedback process. Consensus was pre-determined at 70% of agreement for both importance and relevance of an item. Data were analysed using descriptive statistics and qualitative content analysis of comments provided in each round. Twenty-eight experts working in dementia, language and communication participated in the Delphi survey. Qualitative analysis resulted in the addition of five items, of which three reached the required consensus in Round 3. Consensus was established for 35/37 items in three rounds. The pilot version of the CoSNAT-D demonstrates adequate content validity and face validity. The use of the CoSNAT-D may assist a range of healthcare professionals in the decision-making process about appropriate next management steps, and thereby improve the care path for people with dementia and language and communication impairment. The establishment of further psychometric properties is warranted.

An International External Validation and Revision of the PsyMetRiC Cardiometabolic Risk Prediction Algorithm for Young People with Psychosis

IntroductionThe comorbidity between cardiometabolic and psychotic disorders develops early. This is a crucial window of opportunity to reduce excess morbidity and mortality. Recently, a cardiometabolic risk prediction algorithm for young people with psychosis, the psychosis metabolic risk calculator (PsyMetRiC) was developed and externally validated in the UK. However, its international transportability is unknown.ObjectivesWe performed the first international validation study of PsyMetRiC in Lausanne, Switzerland, and examined whether additional variables (clinical and/or genetic) may improve the predictive performance of the algorithmMethodsWe included people aged 16-35y with psychosis from the PsyMetab cohort, who did not have MetS at baseline, and who had 1-6y follow-up data. The PsyMetRiC partial (age, sex, ethnicity, body mass index, smoking status, and prescription of a metabolically-active antipsychotic) and full (also including high-density lipoprotein and triglycerides) algorithms were applied. Predictive performance was assessed using measures of discrimination (C-statistic) and calibration (calibration plots). Recalibration steps included refitting the intercept and/or slope if necessary. Additional variables (e.g. speed of weight gain, polygenic risk scores) were added to the model and predictive performance was reassessed.ResultsWe included 545 participants. The discrimination performance of both PsyMetRiC algorithms was good (C&gt;0.75), and calibration plots showed good agreement between observed and predicted risk. Additional analyses to be conducted.ConclusionsPsyMetRiC is likely to be generalizable for use in Switzerland, suggesting that PsyMetRiC may also be suitable for use in other European populations. While additional international validations are required, these findings are an encouraging step toward an international cardiometabolic risk prediction algorithm for young people with psychosis.DisclosureNo significant relationships.