Youden's Criterion Research Articles

Evaluation of interleukin-6 in synovial fluid in periprosthetic joint infection of the elbow.

Searching for quick determinable biomarkers with high sensitivity and specificity is necessary to improve and optimise the early diagnosis of periprosthetic elbow infection (PEI). Therefore, this study's objective was to evaluate the diagnostic value of synovial fluid interleukin-6 (IL-6) levels for diagnosing PEI in total elbow arthroplasty. Twelve prospective enrolled patients underwent total elbow arthroplasty revision surgery, during which synovial fluid was obtained. Between the initial implantation and the revision procedure were 33.5 ± 41months (range, 2-144months). Synovial fluid was collected for immediate IL-6 analysis parallel to the revision surgery. Furthermore, microbiological samples were obtained and analysed. Two groups were defined based on the microbiological results: non-infection and infection group. The ability of synovial fluid IL-6 analysis to predict infection status was explored using receiver operating characteristic curves and further statistical analysis. Synovial fluid IL-6 analysis had a good diagnostic accuracy of 83% for PEI with an area under the curve of 0,79 and an ideal cutoff value (determined using Youden's criterion) of 15244pg/mL. This is the first study to clinically evaluate IL-6 as a diagnostical marker for periprosthetic joint infection (PJI) in total elbow arthroplasty. Our results suggest a good accuracy and high sensitivity for IL-6 to identify a PEI. The analysis of IL-6 can improve surgical decision-making regarding managing total elbow arthroplasty in terms of one- or two-staged revision. IL-6 can play an important role in the perioperative differentiation of infected and non-infected situations.

Using item response theory to estimate interpretation threshold values for the Frailty Index in community dwelling older adults

BackgroundAlthough the frailty index (FI) is designed as a continuous measure of frailty, thresholds are often needed to guide its interpretation. This study aimed to introduce and demonstrate the utility of an item response theory (IRT) method in estimating FI interpretation thresholds in community-dwelling adults and to compare them with cutoffs estimated using the receiver operating characteristics (ROC) method. MethodsA sample of 1,149 community-dwelling adults (mean[SD], 68[7] years) participated in this cross-sectional study. Participants completed a multi-domain geriatric screen from which the 40-item FI and 3 clinical anchors were computed – namely, (i)self-reported mobility limitations (SRML), (ii)"fair" or "poor" self-rated health (SRH), and (iii) restricted life-space mobility (RLSM). Participants were classified as having SRML-1 if they responded "Yes" to either of the 2 questions regarding walking and stair climbing difficulty and SRML-2 if they reported having walking and stair climbing difficulty. Participants with a Life Space Assessment score <60 points were classified as having RLSM. Threshold values for all anchor questions were estimated using the IRT method and ROC analysis with Youden criterion. ResultsThe proportions of participants with SRML-1, SRML-2, Fair/Poor SRH, and RLSM were 21 %, 8 %, 22 %, and 9 %, respectively. The IRT-based thresholds for SRML-2 (0.26), fair/poor SRH (0.29), and RLSM (0.32) were significantly higher than those for SRML-1 (0.18). ROC-based FI cutoffs were significantly lower than IRT-based values for SRML-2, SRH, and RLSM (0.12 to 0.17), and they varied minimally and non-systematically across the anchors. ConclusionsThe IRT method identifies biologically plausible FI thresholds that could meaningfully complement and contextualize existing thresholds for defining frailty.

Abstract 18359: Association of Depressive Symptoms and Risk of 30- and 90-day Hospital Admissions in Patients With a New or Worsening Diagnosis of Peripheral Artery Disease

Introduction: Patients diagnosed with Peripheral Artery Disease (PAD) often present with a complex profile of comorbidities, including a high mental health burden. Depressive symptoms are associated with worse long-term PAD outcomes, but it is unknown whether they translate into a higher short term hospital admission. Methods: Patients with a new or worsening PAD diagnosis (Rutherford 1-3) enrolled at US in the PORTRAIT registry from 2011-2015 were included. The 8-item Patient Health Questionnaire assessed depressive symptoms (scores 0 to 24, higher scores more depressive symptoms). The Youden Criterion based on time-dependent receiver operator curves was used to describe high vs. low-risk admission groups. Adjusted Cox regression models generated risk estimates associated with continuous PHQ-8 scores and all-cause, cumulative 30- and 90-day admissions based on patients’ medical records. Results: We included 669 patients in the analysis (mean age 68.6 ± 9.6 years, 57.6% male, 73.0% white). The mean PHQ-8 Score was 4.8 ± 5.2; 61.9% was classified as low- (PHQ-8 &lt;5) vs. 38.1% high-risk (PHQ-8 ≥ 5) for admissions based on the Youden Criterion. Patients in the low-risk vs. high-risk group had admission rates of 7.7% [95% CI 5.5-10.7] vs. 12.9% [95% CI 9.5-17.5] at 30 days (p-value: 0.023) and 16.2 [95% CI 13.1-20.0] vs. 25.6% [95% CI 21.0-31.0] at 90 days (p=0.002). In the adjusted model, depressive symptoms (per 1-unit increase) were independently and proportionally associated with 30-day (HR=1.06, 95% CI 1.01-1.11; p=0.026) and 90-day (HR=1.04, 95% CI 1.01-1.08; p=0.021) admissions following PAD diagnosis (e.g. those with scores &gt;20 had a &gt;20% or &gt;30% 30- and 90-day admission risk, respectively) (Figure 1). Conclusion: Thirty- and 90-day admission risk for patients with a new or worsening PAD diagnosis is high, especially for those with depressive symptoms. Value-based PAD care should include screening and integrated care pathways for depression to mitigate this risk.

242-OR: Defining Targets for Continuous Glucose Monitoring (CGM) after Total Pancreatectomy with Islet Autotransplantation (TPIAT)

Targets for continuous glucose monitoring (CGM) are well established for type 1 and type 2 diabetes. In total pancreatectomy with islet auto-transplant (TPIAT), stricter glycemic targets are needed to avoid metabolic stress on transplanted islets, but no guidelines exist for CGM targets. We aimed to determine CGM targets for TPIAT clinical management by associating CGM metrics with goal hemoglobin A1c (HbA1c) ≤6.5%. Targets for time in range (TIR) 70-140, TIR 70-180, mean CGM glucose, and time in hyperglycemia (&amp;gt;140, &amp;gt;180, &amp;gt;250 mg/dL) were chosen to give good sensitivity and specificity for identifying HbA1c ≤6.5%. We included 256 episodes of 14-day CGM metrics with a concurrent HbA1c value (n=82 patients, age 32.8 [SD 16.6] years at surgery, 70% female) who were ≥0.5 years post TPIAT (median 4.1 years) and wearing Dexcom G6. Most patients had more than 1 HbA1c and corresponding CGM available (median 3.1 per patient). As expected, CGM metrics correlated highly with each other. Table 1 shows “best” (Youden criterion) CGM thresholds and sensitivity for HbA1c ≤6.5%. TIR 70-140 mg/dL ≥50% and TIR 70-180 mg/dL ≥75% may be reasonable targets for patients and providers using CGM data to manage diabetes long-term after TPIAT. Also, time in hyperglycemia should be kept to &amp;lt;20% above 180 mg/dL and &amp;lt;3% above 250 mg/dL. Failure of these goals should prompt re-starting or adjusting insulin therapy. Disclosure Z.Somani: None. J.S.Hodges: None. K.Ramanathan: None. S.Chinnakotla: None. G.Beilman: None. M.Bellin: Consultant; Insulet Corporation, Vertex Pharmaceuticals Incorporated, Research Support; Dexcom, Inc., ViaCyte, Inc.

Estimating cutpoints of gait speed and sit-to-stand test values for self-reported mobility limitations in a cohort of community-dwelling older adults from Singapore: comparing receiver operating characteristic (ROC) analysis with adjusted predictive modelling

ObjectivesClinical interpretability of the gait speed and 5-times sit-to-stand (5-STS) tests is commonly established by comparing older adults with and without self-reported mobility limitations (SRML) on gait speed and 5-STS performance, and estimating clinical cutpoints for SRML using the receiver operating characteristics (ROC) method. Accumulating evidence, however, suggests that the adjusted predictive modeling (APM) method may be more appropriate to estimate these interpretational cutpoints. Thus, we aimed to compare, in community-dwelling older adults, gait speed and 5-STS cutpoints estimated using the ROC and APM methods. DesignCross-sectional study. Setting and ParticipantsThis study analyzed data from 955 community-dwelling independently walking older adults (73%women) aged ≥60 years (mean, 68; range, 60–88). MethodsParticipants completed the 10-metre gait speed and 5-STS tests. Participants were classified as having SRML if they responded "Yes" to either of the 2 questions regarding walking and stair climbing difficulty. Cutpoints for SRML and its component questions were estimated using ROC analysis with Youden criterion and the APM method. ResultsThe proportions of participants with self-reported walking difficulty, self-reported stair climbing difficulty, and SRML were 10%, 19%, and 22%, respectively. Gait speed and 5-STS time were moderately correlated with each other (r=-0.56) and with the self-reported measures (absolute r-values, 0.39–0.44). ROC-based gait speed cutpoints were 0.14 to 0.16 m/s greater than APM-based cutpoints (P < 0.05) whilst ROC-based 5-STS time cutpoints were 0.8 to 3.3 s lower than APM-based cutpoints (P < 0.05 for walking difficulty). Compared with ROC-based cutpoints, APM-based cutptoints were more precise and they varied monotonically with self-reported walking difficulty, self-reported stair climbing difficulty, and SRML. Conclusions and implicationsIn a sample of 955 older adults, our findings of precise and biologically plausible gait speed and 5-STS cutpoints for SRML estimated using the APM method indicate that this promising method could potentially complement or even replace traditional ROC methods.

Minimal Clinically Important Difference Estimates Are Biased by Adjusting for Baseline Severity, Not by Regression to the Mean.

Minimal Clinically Important Difference Estimates Are Biased by Adjusting for Baseline Severity, Not by Regression to the Mean.

Commercial Synovial Antibody Testing is No Better Than Traditional Culture in Identification of Pathogen(s) Causing Periprosthetic Joint Infection.

Identification of infective organism causing periprosthetic joint infections (PJIs) is crucial to tailor the best combination of surgical and antimicrobial treatment. Traditional culture, with all its limitations, has been utilized for this purpose. A synovial fluid antibody assay against some common pathogens has been introduced by a commercial entity recently. This study aimed to determine if the antibody testing could be used as a proxy to traditional culture, and whether it provided additional information, in the setting of PJI. A retrospective study was conducted of patients who underwent revision total hip and knee arthroplasty between January 2019 and 2020. Aspirated synovial fluid was sent for analyses including the commercial antibody testing. All patients had samples harvested for culture per standard of care. Results of the antibody testing and culture, in terms of concordance, were compared. Receiver operating characteristic curve and Youden's criterion were used to compare the 2 methods. A total of 419 patients were included. Using the International Consensus Meeting criteria as reference standard for PJI, antibody testing had a sensitivity and specificity of 40.5% and 93.4%, respectively. There were 59.5% false negative results with antibody testing compared with 50% for culture. Of the 12 patients who had positive results in both tests, 5 (41.7%) had discordant pathogens identified in each test. Synovial fluid antibody testing does not provide clinical benefit when compared to traditional cultures for PJI diagnosis. The antibody testing had a low sensitivity and a high rate of discordance with culture, when both tests were positive.

Echocardiographic-derived Pulmonary Artery Pulsatility Index: towards non-invasive evaluation of right ventricular function

Abstract Funding Acknowledgements Type of funding sources: None. Background. Pulmonary artery pulsatility index (PAPi)(1) is a powerful predictor of right ventricular failure in patients with acute inferior myocardial infarction(2) and in patients with heart failure undergoing LVAD implantation(3). PAPi derivation requires invasive right heart catheterism (RHC), thus limiting availability and seriate assessment of right ventricular function. Purpose. Aim of the study was to evaluate accuracy and agreement of echocardiographic derived PAPi (ePAPi) compared to right heart catheterism derived PAPi in heart failure with reduced ejection fraction (HFrEF) patients. Methods. ePAPi was defined as the ratio of pulmonary artery pulse pressure (sPAP – dPAP) to right atrial pressure (RAP). Systolic pulmonary artery pressure (sPAP) was determined from tricuspid regurgitation (TR) velocity using the simplified Bernoulli equation(4): sPAP = 4 x (peak TR jet velocity)2 + RA pressure. Diastolic pulmonary artery pressure (dPAP) was calculated as: dPAP = 4 x (end-diastolic pulmonary regurgitant velocity)2 + RA pressure. Simplified ePAPi, defined as peak TR pressure to RA pressure ratio was also investigated. Pearson and Spearman correlation tests were performed. A Bland-Altman plot analysis was performed to assess agreement between ePAPi and invasive PAPi. ROC curves were made to assess ePAPi accuracy in identifying patients with low PAPi (defined as PAPi &amp;lt; 2 and PAPi &amp;lt; 3.65). Results. 66 HFrEF patients (age 59 ± 10 years, 63% males, mean EF: 35 ± 9%) underwent RHC and blinded echocardiogram in a single center Cardiology Departement. Mean invasive derived PAPi was 4.4 ± 3.6, while ePAPi was 3.9 ± 2.3. ePAPi showed an excellent correlation with invasive PAPi (Pearson r: 0.80, p &amp;lt; 0.001; Spearman rho: 0.83, p &amp;lt; 0.001) and good agreement as shown in Bland Altman plot (figure 1). In ROC analysis, ePAPi accurately identified patients with low hemodynamic PAPi &amp;lt; 2 (Sensibility: 100%; Specificity: 87.2%; AUC: 0.97; Youden criterion: ePAPi &amp;lt; 2.3) and PAPi &amp;lt; 3.65 (Sensibility: 81.8%; Specificity: 84%; AUC: 0.89; Youden criterion: ePAPi &amp;lt; 3.6)(figure 2). Simplified ePAPi also showed good correlation and agreement (Pearson r: 0.58, p &amp;lt; 0.001; Spearman rho: 0.81, p &amp;lt; 0.001). Conclusions. In patients with HFrEF, echocardiographic derived PAPi showed a good agreement and correlation with invasive derived PAPi. ePAPi was also accurate in identifying patients with low PAPi values associated with poor outcomes and may be of interest for non-invasive right ventricular function seriate assessment. Further studies are needed to investigate prognostic implications. Abstract Figure. Abstract Figure 2

Validity and repeatability of the Pediatric Allergy Questionnaire for Athletes (AQUAped) for the screening of atopy.

High atopy prevalence has been reported in athletes. Having an age-specific questionnaire for predicting atopy is important for an optimal management of young athletes. The study objectives were as follows: (i) developing a scoring system for the Pediatric Allergy Questionnaire for Athletes (AQUAped); (ii) identifying the optimal age target within the range 7-14years; (iii) assessing AQUAped validity and repeatability in the identified target population. A total of 133 young athletes (age 7-14years) were recruited. Following a screening visit, the participants filled AQUAped at baseline (T0) and after 7days (T1), concomitantly undergoing skin prick testing. Using atopy as the gold standard (positivity to ≥1 aeroallergen), the 12 core items were scored based on their likelihood ratios, and a total score was calculated. The optimal cut-off was identified based on the Youden's criterion. The repeatability of AQUAped was assessed through the intra-cluster correlation coefficient (ICC). The optimal age target was identified as the largest age range associated with an acceptable cross-validated area under the receiver operating characteristic curve (AUC≥0.70) and an excellent ICC (≥0.75). Forty (30%) children were atopic; the optimal age target was 10-14years (cross-validated AUC=0.70, ICC=0.81). AQUAped total score ranged from -26 to 75, and only 5% of non-atopic children had AQUAped≥24. AQUAped≥2 had 82% specificity, 60% sensitivity, and 74% overall accuracy. Developing and testing a scoring system for AQUAped showed that it is a valid and reliable tool for the screening of atopy in young athletes aged 10-14years.

Conventional Ultrafiltration During Elective Cardiac Surgery and Postoperative Acute Kidney Injury

Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) serves to hemoconcentrate blood volume to avoid allogeneic blood transfusions. Previous studies have determined CUF volumes as a continuous variable are associated with postoperative acute kidney injury (AKI) after cardiac surgery, but optimal weight-indexed volumes that predict AKI have not been described. Retrospective cohort. Single-center university hospital. A total of 1,641 consecutive patients who underwent elective cardiac surgery between June 2013 and December 2015. The CUF volume was removed during CPB in all participants as part of routine practice. The authors investigated the association of dichotomized weight-indexed CUF volume removal with postoperative AKI development to provide pragmatic guidance for clinical practice at the authors' institution. Primary outcomes of postoperative AKI were defined by the Kidney Disease: Improving Global Outcomes staging criteria and dichotomized, weight-indexed CUF volumes (mL/kg) were defined by (1) extreme quartiles (<Q1 v >Q3) and (2) Youden's criterion that best predicted AKI development. Multivariate logistic regression models were developed to test the association of these dichotomized indices with AKI status. Postoperative AKI occurred in 827 patients (50.4%). Higher CUF volumes were associated with AKI development by quartiles (CUF >Q3 = 32.6 v CUF < Q1 = 10.4 mL/kg; odds ratio [OR] = 1.68, 95% CI: 1.19-2.3) and Youden's criterion (CUF ≥ 32.9 v CUF <32.9 mL/kg; OR = 1.60, 95% CI: 1.21-2.13). Despite similar intraoperative nadir hematocrits among groups (p = 0.8), higher CUF volumes were associated with more allogeneic blood transfusions (p = 0.002) and longer lengths of stay (p < 0.001). Removal of weight-indexed CUF volumes > 32 mL/kg increased the risk for postoperative AKI development. Importantly, CUF volume removal of any amount did not mitigate allogeneic blood transfusion during elective cardiac surgery. Prospective studies are needed to validate these findings.

The diagnostic accuracy of adjusted unconventional indices for adrenal vein sampling in the diagnosis of primary aldosteronism subtypes.

Simple unconventional indices did not demonstrate a satisfactory accuracy for diagnosing unilateral primary aldosteronism when adrenal vein sampling is not bilaterally selective. This study aimed to evaluate the reliability of clinical/imaging-corrected unconventional indices for adrenal vein sampling in predicting unilateral primary aldosteronism. Data of all consecutive patients with primary aldosteronism subtyped with adrenal vein sampling, referred to two Italian centers, were analyzed retrospectively. All patients with proved unilateral aldosterone hypersecretion underwent adrenalectomy. Unilateral disease was diagnosed in 58 cases (54.2%) and idiopathic hyperaldosteronism in 49 individuals (45.8%). The monoadrenal index (aldosterone-to-cortisol ratio in the adrenal vein) showed high accuracy in predicting ipsilateral disease and moderate accuracy in predicting contralateral aldosterone hypersecretion. The monolateral index (aldosterone-to-cortisol ratio in the adrenal vein vs. peripheral blood) revealed moderate accuracy in predicting ipsilateral disease and high accuracy in predicting contralateral aldosterone hypersecretion. Lesion side- and hypokalemia-corrected ROC curves for these unconventional indices revealed a significant improvement in the reliability of predicting ipsilateral/contralateral disease, reaching high accuracy in all models. For an immediate clinical application of our results, the adjusted cut-offs were calculated, according to the Youden's criterion and to a pre-established specificity of 95%, for all possible combinations of lesion side at imaging and presence/absence of hypokalemia. This study demonstrated the high diagnostic accuracy of clinical-/imaging-corrected unconventional indices for adrenal vein sampling in the diagnosis of primary aldosteronism subtypes and suggests the use of these adjusted indices to select patients for adrenalectomy when adrenal vein sampling is not bilaterally selective.

Optimal Thresholding of Predictors in Mineral Prospectivity Analysis

Some methods for analysing mineral prospectivity, especially the weights of evidence technique, require the predictor variables to be binary values. When the original evidence data are numerical values, such as geochemical indices, they can be converted to binary values by thresholding. When the evidence layer is a spatial feature such as a geological fault system, it can be converted to a binary predictor by buffering at a suitable cut-off distance. This paper reviews methods for selecting the best threshold or cut-off value and compares their performance. The review covers techniques which are well known in prospectivity analysis as well as unfamiliar techniques borrowed from other literature. Methods include maximisation of the estimated contrast, Studentised contrast, $$\chi ^2$$ test statistic, Youden criterion, statistical likelihood, Akman–Raftery criterion, and curvature of the capture–efficiency curve. We identify connections between the different methods, and we highlight a common technical error in their application. Simulation experiments indicate that the Youden criterion has the best performance for selection of the threshold or cut-off value, assuming that a simple binary threshold relationship truly holds. If the relationship between predictor and prospectivity is more complicated, then the likelihood method is the most easily adaptable. The weights-of-evidence contrast performs poorly overall. These conclusions are supported by our analysis of data from the Murchison goldfields, Western Australia. We also propose a bootstrap method for calculating standard errors and confidence intervals for the location of the threshold.

Impact of high-dose norepinephrine during intra-hospital damage control resuscitation of traumatic haemorrhagic shock: A propensity-score analysis

IntroductionThe use of norepinephrine (NE) during uncontrolled haemorrhagic shock (HS) has mostly been investigated in experimental studies. Clinical data including norepinephrine dose and its impact on fluid resuscitation and organ function are scarce. We hypothesized that there is great variability in NE use and that high doses of NE could lead to increased organ dysfunction as measured by the sequential organ failure assessment (SOFA). MethodWe included patients with HS (systolic blood pressure < 90 mmHg in severely injured patients) who required haemostasis surgery and a transfusion of more than 4 packed red blood cells (PRBC) in the first 6 h of admission and the used of norepinephrine infusion to maintain the blood pressure goal, between admission and the end of haemostasis surgery in a prospective trauma database. A ROC curve determined that, using Youden's criterion, a dose of NE ≥ 0.6 µg/kg/min was the optimal threshold associated with intrahospital mortality. Patients were compared according to this threshold in a propensity score (PS) model. In a generalized linear mixed model, we searched for independent factors associated with a SOFA ≥ 9 at 24 h ResultsA total of 89 patients were analysed. Fluid infusion rate ranged from 1.43 to 57.9 mL/kg/h and norepinephrine infusion rate from 0.1 to 2.8 µg/kg/min. The HDNE group received significantly less fluid than the LDNE group. This dose is associated with a higher SOFA score at 24h: 9 (7–10) vs. 7 (6–9) (p = 0.003). Factors independently associated with a SOFA score ≥ 9 at 24 h were maximal norepinephrine rate ≥ 0.6 µg/kg/min (OR 6.69, 95% CI 1.82 – 25.54; p = 0.004), non-blood resuscitation volume < 9 mL/kg/h (OR 3.98, 95% CI 1.14 – 13.95; p = 0.031) and lactate at admission ≥ 5 mmol/L (OR 5.27, 95% CI 1.48 – 18.77; p = 0.010) ConclusionHigh dose of norepinephrine infusion is associated with deleterious effects as attested by a higher SOFA score at 24 h and likely hypovolemia as measured by reduced non-blood resuscitation volume. We did not find any significant difference in mortality over the long term.

Overrating Classifier Performance in ROC Analysis in the Absence of a Test Set: Evidence from Simulation and Italian CARATkids Validation.

The use of receiver operating characteristic curves, or "ROC analysis," has become quite common in biomedical research to support decisions. However, sensitivity, specificity, and misclassification rates are still often estimated using the training sample, overlooking the risk of overrating the test performance. A simulation study was performed to highlight the inferential implications of splitting (or not) the dataset into training and test set. The normality assumption was made for the classifier given the disease status, and the Youden's criterion considered for the detection of the optimal cutoff. Then, an ROC analysis with sample split was applied to assess the discriminant validity of the Italian version of the Control of Allergic Rhinitis and Asthma Test (CARATkids) questionnaire for children with asthma and rhinitis, for which recent studies may have reported liberal performance estimates. The simulation study showed that both single split and cross-validation (CV) provided unbiased estimators of sensitivity, specificity, and misclassification rate, therefore allowing computation of confidence intervals. For the Italian CARATkids questionnaire, the misclassification rate estimated by fivefold CV was 0.22, with 95% confidence interval 0.14 to 0.30, indicating an acceptable discriminant validity. Splitting into training and test set avoids overrating the test performance in ROC analysis. Validated through this method, the Italian CARATkids is valid for assessing disease control in children with asthma and rhinitis.

Automatic classification of dopamine transporter SPECT: deep convolutional neural networks can be trained to be robust with respect to variable image characteristics.

This study investigated the potential of deep convolutional neural networks (CNN) for automatic classification of FP-CIT SPECT in multi-site or multi-camera settings with variable image characteristics. The study included FP-CIT SPECT of 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls, and 438 Parkinson's disease patients. SPECT images were smoothed with an isotropic 18-mm Gaussian kernel resulting in 3 different PPMI settings: (i) original (unsmoothed), (ii) smoothed, and (iii) mixed setting comprising all original and all smoothed images. A deep CNN with 2,872,642 parameters was trained, validated, and tested separately for each setting using 10 random splits with 60/20/20% allocation to training/validation/test sample. The putaminal specific binding ratio (SBR) was computed using a standard anatomical ROI predefined in MNI space (AAL atlas) or using the hottest voxels (HV) analysis. Both SBR measures were trained (ROC analysis, Youden criterion) using the same random splits as for the CNN. CNN and SBR trained in the mixed PPMI setting were also tested in an independent sample from clinical routine patient care (149 with non-neurodegenerative and 149 with neurodegenerative parkinsonian syndrome). Both SBR measures performed worse in the mixed PPMI setting compared to the pure PPMI settings (e.g., AAL-SBR accuracy = 0.900 ± 0.029 in the mixed setting versus 0.957 ± 0.017 and 0.952 ± 0.015 in original and smoothed setting, both p < 0.01). In contrast, the CNN showed similar accuracy in all PPMI settings (0.967 ± 0.018, 0.972 ± 0.014, and 0.955 ± 0.009 in mixed, original, and smoothed setting). Similar results were obtained in the clinical sample. After training in the mixed PPMI setting, only the CNN provided acceptable performance in the clinical sample. These findings provide proof of concept that a deep CNN can be trained to be robust with respect to variable site-, camera-, or scan-specific image characteristics without a large loss of diagnostic accuracy compared with mono-site/mono-camera settings. We hypothesize that a single CNN can be used to support the interpretation of FP-CIT SPECT at many different sites using different acquisition hardware and/or reconstruction software with only minor harmonization of acquisition and reconstruction protocols.

Complementarity of NUTRIC score and Subjective Global Assessment for predicting 28-day mortality in critically ill patients

AimsTo compare the prognostic power of nutritional screening (NUTRIC score) and Subjective Global Assessment (SGA), executed alone or their complementarity, for predicting 28-day mortality risk in ICU patients. We also aimed to identify the cut-off point obtained in the NUTRIC that presented the best validity parameters for predicting mortality in this population. MethodsA sample of 159 patients was evaluated in the first 24 hours of ICU admission. Modified NUTRIC score was performed (without interleucina-6). ROC curve and Youden criterion were used to identify the best cut-off point. Poisson regression and the number needed to screen (NNS) were used to test the complementarity between the tools and their ability to predict 28-day mortality. ResultsA sample of 159 patients was evaluated (51% male, 56.6 ± 20 years) and the APACHE II, SOFA and NUTRIC score medians were 22 (IQR:15;26), 6 (IQR:2;9) and 3 (IQR: 2;5), respectively. Almost 60% of the patients were malnourished (SGA B or C) and 32.7% died during 28-day follow-up. The area under ROC curve for NUTRIC score was 0.79. Using a new cutoff (NUTRIC score ≥ 4), patients with nutritional risk have a 28-day mortality risk almost 6 times higher than subjects without nutritional risk. Patients classified as SGA C showed a 28-day mortality risk 2.19 times higher compared to nourished ones. Evaluating the complementarity of the tools, patients classified as nutritional risk (NUTRIC score ≥ 4) and SGA C showed a 28-day mortality risk 7 times higher and a lower NNS when compared to those patients with a NUTRIC < 4 and any SGA category. ConclusionsA new cutoff value was identified for this population. Simultaneous SGA assessment in patients with nutritional risk may enhance the predictive power of 28-day mortality, providing better identification of higher risk patients who may benefit from a more aggressive nutritional therapy.

Chronic sleep reduction in adolescents-clinical cut-off scores for the Chronic Sleep Reduction Questionnaire (CSRQ).

The Chronic Sleep Reduction Questionnaire is a validated questionnaire that measures symptoms of prolonged insufficient and/or poor sleep and therefore accounts for individuals' sleep need and sleep debt. This study extends its psychometric properties by providing cut-off scores, using a matched sample of 298 healthy adolescents (15.38±1.63years, 37.9% male, mean Chronic Sleep Reduction Questionnaire score: 32.98±6.51) and 298 adolescents with insomnia/delayed sleep-wake phase disorder (15.48±1.62years; 37.9% male, mean Chronic Sleep Reduction Questionnaire score: 42.59±7.06). We found an area under the curve of 0.84 (95% confidence interval: 0.81-0.87). Cut-off scores for optimal sensitivity, optimal specificity and based on Youden's criterion are provided. These cut-off scores are highly relevant for use of the Chronic Sleep Reduction Questionnaire in future studies and clinical practice.

Quantitative Evaluation of Therapeutic Response by FDG-PET-CT in Metastatic Breast Cancer.

To assess the therapeutic response for metastatic breast cancer with (18)F-FDG position emission tomography (PET), this retrospective study aims to compare the performance of six different metabolic metrics with PERCIST, PERCIST with optimal thresholds, and an image-based parametric approach. Thirty-six metastatic breast cancer patients underwent 128 PET scans and 123 lesions were identified. In a per-lesion and per-patient analysis, the performance of six metrics: maximum standardized uptake value (SUVmax), SUVpeak, standardized added metabolic activity (SAM), SUVmean, metabolic volume (MV), total lesion glycolysis (TLG), and a parametric approach (SULTAN) were determined and compared to the gold standard (defined by clinical assessment and biological and conventional imaging according RECIST 1.1). The evaluation was performed using PERCIST thresholds (for per-patient analysis only) and optimal thresholds (determined by the Youden criterion from the receiver operating characteristic curves). In the per-lesion analysis, 210 pairs of lesion evolutions were studied. Using the optimal thresholds, SUVmax, SUVpeak, SUVmean, SAM, and TLG were significantly correlated with the gold standard. SUVmax, SUVpeak, and SUVmean reached the best sensitivity (91, 88, and 83%, respectively), specificity (93, 95, and 97%, respectively), and negative predictive value (NPV, 90, 88, and 83%, respectively). For the per--patient analysis, 79 pairs of PET were studied. The optimal thresholds compared to the PERCIST threshold did not improve performance for SUVmax, SUVpeak, and SUVmean. Only SUVmax, SUVpeak, SUVmean, and TLG were correlated with the gold standard. SULTAN also performed equally: 83% sensitivity, 88% specificity, and NPV 86%. This study showed that SUVmax and SUVpeak were the best parameters for PET evaluation of metastatic breast cancer lesions. Parametric imaging is helpful in evaluating serial studies.

Holland Sleep Disorders Questionnaire: a new sleep disorders questionnaire based on the International Classification of Sleep Disorders‐2

The primary objectives of this study were to construct a self-assessment questionnaire for sleep disorders based on the International Classification of Sleep Disorders-2, and to evaluate the questionnaire's psychometric properties with respect to its total score and the individual scores for each of the six sleep disorders. In total, 1269 patients, clinically diagnosed with a sleep disorder, and 412 subjects without sleep complaints were enrolled into this study. Principal components analysis confirmed that the Holland Sleep Disorders Questionnaire differentially represented the six symptom clusters associated with International Classification of Sleep Disorders-2 classifications. The Holland Sleep Disorders Questionnaire's total score distinguished patients with a clinically diagnosed sleep disorder from individuals without sleep complaints, with area under the receiver operating curve P(A) of 0.95. The internal reliability coefficient alpha was 0.90 and, applying the Youden criterion as cutoff score, the overall accuracy was 88% (κ: 0.75). Subsequently, the six diagnostic groups of sleep-disordered patients could be differentiated reliably, with P(A) values ranging between 0.69 and 0.95, alpha coefficients ranging between 0.73 and 0.81 and an overall percentage of 85% correctly classified patients (κ = 0.80), indicating a substantial to excellent agreement between the primary diagnoses and the Holland Sleep Disorders Questionnaire classifications.