Validation of olfactory deficit as a biomarker of Alzheimer disease

AbstractBackground:We evaluated smell identification as a biomarker for Alzheimer disease (AD) by assessing its utility in differentiating normal aging from an amnestic disorder and determining its predictive value for conversion from amnestic mild cognitive impairment (aMCI) to AD.Methods:Cross-sectional study (AD = 262, aMCI = 110, controls = 194) measuring smell identification (University of Pennsylvania Smell Identification Test [UPSIT]) and cognitive status was performed, as well as longitudinal analysis of aMCI participants (n = 96) with at least 1 year follow-up (mean 477.6 ± 223.3 days), to determine conversion by National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria.Results:Odor identification and disease status were highly correlated after correcting for age, sex, and APOE (p < 0.001). Receiver operating characteristic (ROC)/area under the curve (AUC) was similar for the 40-item UPSIT, the top 10 smells in our study, and the 10-item subset previously proposed. Smeller/nonsmeller based on the 10-item subset with a cutoff of 7 (≤7, nonsmeller; >7, smeller) had a sensitivity and specificity of 88% and 71% for identifying AD and 74% sensitivity and 71% specificity for identifying an amnestic disorder. A total of 36.4% of participants with impaired olfaction and 17.3% with intact olfaction converted to AD (p = 0.03). The ROC/AUC for prediction of conversion to AD was 0.62.Conclusions:Olfactory identification deficit is a useful screening tool for AD-related amnestic disorder, with sensitivity and specificity comparable to other established biomarkers, with benefits such as ease of administration and low cost. Olfactory identification deficit can be utilized to stratify risk of conversion from aMCI to AD and enrich clinical trials of disease-modifying therapy.Classification of evidence:This study provides Class III evidence that smell identification (10-item UPSIT subset) accurately identifies patients with amnestic disorders.

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Development and Validation of Two Self-Reported Tools for Insulin Resistance and Hypertension Risk Assessment in A European Cohort: The Feel4Diabetes-Study

Nutrients ◽

10.3390/nu12040960 ◽

2020 ◽

Vol 12 (4) ◽

pp. 960

Author(s):

Spyridon Kanellakis ◽

Christina Mavrogianni ◽

Kalliopi Karatzi ◽

Jaana Lindstrom ◽

Greet Cardon ◽

...

Keyword(s):

Insulin Resistance ◽

Risk Assessment ◽

High Risk ◽

Sensitivity And Specificity ◽

Low Cost ◽

Area Under The Curve ◽

Assessment Tools ◽

Screening Tools ◽

Model Assessment ◽

Sugary Drinks

Early identification of type 2 diabetes mellitus (T2DM) and hypertension (HTN) risk may improve prevention and promote public health. Implementation of self-reported scores for risk assessment provides an alternative cost-effective tool. The study aimed to develop and validate two easy-to-apply screening tools identifying high-risk individuals for insulin resistance (IR) and HTN in a European cohort. Sociodemographic, lifestyle, anthropometric and clinical data obtained from 1581 and 1350 adults (baseline data from the Feel4Diabetes-study) were used for the European IR and the European HTN risk assessment index respectively. Body mass index, waist circumference, sex, age, breakfast consumption, alcohol, legumes and sugary drinks intake, physical activity and sedentary behavior were significantly correlated with Homeostatic Model Assessment of IR (HOMA-IR) and/or HTN and incorporated in the two models. For the IR index, the Area Under the Curve (AUC), sensitivity and specificity for identifying individuals above the 75th and 95th of HOMA-IR percentiles were 0.768 (95%CI: 0.721–0.815), 0.720 and 0.691 and 0.828 (95%CI: 0.766–0.890), 0.696 and 0.778 respectively. For the HTN index, the AUC, sensitivity and specificity were 0.778 (95%CI: 0.680–0.876), 0.667 and 0.797. The developed risk assessment tools are easy-to-apply, valid, and low-cost, identifying European adults at high risk for developing T2DM or having HTN.

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A novel model to quantify balance alterations in older adults based on the center of pressure (CoP) measurements with a cross-sectional study

PLoS ONE ◽

10.1371/journal.pone.0256129 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0256129

Author(s):

Ángel Gabriel Estévez-Pedraza ◽

Lorena Parra-Rodríguez ◽

Rigoberto Martínez-Méndez ◽

Otniel Portillo-Rodríguez ◽

Zoraida Ronzón-Hernández

Keyword(s):

Older Adults ◽

Fall Risk ◽

Center Of Pressure ◽

Low Cost ◽

Area Under The Curve ◽

Public Health Problem ◽

Cross Sectional Study ◽

Community Dwelling ◽

Mean Velocity ◽

Cross Sectional

Background The timely detection of fall risk or balance impairment in older adults is transcendental because, based on a reliable diagnosis, clinical actions can be taken to prevent accidents. This study presents a statistical model to estimate the fall risk from the center of pressure (CoP) data. Methods This study is a cross-sectional analysis from a cohort of community-dwelling older adults aged 60 and over living in Mexico City. CoP balance assessments were conducted in 414 older adults (72.2% females) with a mean age of 70.23 ± 6.68, using a modified and previously validated Wii Balance Board (MWBB) platform. From this information, 78 CoP indexes were calculated and analyzed. Multiple logistic regression models were fitted in order to estimate the relationship between balance alteration and the CoP indexes and other covariables. Results The CoP velocity index in the Antero-Posterior direction with open eyes (MVELAPOE) had the best value of area under the curve (AUC) to identify a balance alteration (0.714), and in the adjusted model, AUC was increased to 0.827. Older adults with their mean velocity higher than 14.24 mm/s had more risk of presenting a balance alteration than those below this value (OR (Odd Ratio) = 2.94, p<0.001, 95% C.I.(Confidence Interval) 1.68–5.15). Individuals with increased age and BMI were more likely to present a balance alteration (OR 1.17, p<0.001, 95% C.I. 1.12–1.23; OR 1.17, p<0.001, 95% C.I. 1.10–1.25). Contrary to what is reported in the literature, sex was not associated with presenting a balance alteration (p = 0.441, 95% C.I. 0.70–2.27). Significance The proposed model had a discriminatory capacity higher than those estimated by similar means and resources to this research and was implemented in an embedded standalone system which is low-cost, portable, and easy-to-use, ideal for non-laboratory environments. The authors recommend using this technology to support and complement the clinical tools to attend to the serious public health problem represented by falls in older adults.

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2479

Journal of Clinical and Translational Science ◽

10.1017/cts.2017.282 ◽

2017 ◽

Vol 1 (S1) ◽

pp. 80-80

Author(s):

Scott Martin Vouri ◽

Seth Strope ◽

Margaret Olsen

Keyword(s):

Urinary Retention ◽

Sensitivity And Specificity ◽

Predictive Value ◽

Area Under The Curve ◽

Urinary Catheterization ◽

Billing Data ◽

Cross Sectional ◽

Physician Billing ◽

Diagnosis Codes ◽

Urology Clinic

OBJECTIVES/SPECIFIC AIMS: We evaluated the accuracy of diagnosis and procedure codes to identify acute urinary retention (AUR) due to lack of existing validation studies. METHODS/STUDY POPULATION: We performed a cross-sectional validation study at a single medical institution in the emergency department (ED) and outpatient Urology Clinic in men ≥45 years. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes 788.20, 788.21, 788.29 for urinary retention and Current Procedural Terminology, Fourth Edition (CPT-4) codes 51701, 51702, 51703 for urinary catheterization were used to identify men with potential AUR. Four algorithms using ICD-9-CM and CPT-4 codes were compared against medical record review. Sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were calculated for both the ED and Urology Clinic. RESULTS/ANTICIPATED RESULTS: A total of 333 treated and released men in the ED were identified using facility billing data, and 245 men using physician billing data in the Urology Clinic were identified using the codes for urinary retention or urinary catheterization. Of the 4 algorithms, any ICD-9-CM diagnosis code for urinary retention was the preferred algorithm with a sensitivity and specificity of 0.95 and 0.91 using ED facility billing data and a sensitivity and specificity of 0.95 and 0.58 using Urology physician billing data. DISCUSSION/SIGNIFICANCE OF IMPACT: Use of the ICD-9-CM diagnosis codes for urinary retention performed well at identifying AUR in the ED. This study provides justification to use urinary retention diagnosis codes (specifically 788.20 and 788.29) in future studies to identify AUR using administrative data, especially in the ED.

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Comparative Diagnostic Accuracy of the ACE-III, MIS, MMSE, MoCA, and RUDAS for Screening of Alzheimer Disease

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000469658 ◽

2017 ◽

Vol 43 (5-6) ◽

pp. 237-246 ◽

Cited By ~ 31

Author(s):

Jordi A. Matías-Guiu ◽

María Valles-Salgado ◽

Teresa Rognoni ◽

Frank Hamre-Gil ◽

Teresa Moreno-Ramos ◽

...

Keyword(s):

Alzheimer Disease ◽

Diagnostic Accuracy ◽

Area Under The Curve ◽

Cross Sectional Study ◽

Screening Tests ◽

Cross Sectional ◽

Diagnostic Capacity ◽

State Examination ◽

Diagnostic Properties ◽

Addenbrooke’S Cognitive Examination

Background: Our aim was to evaluate and compare the diagnostic properties of 5 screening tests for the diagnosis of mild Alzheimer disease (AD). Methods: We conducted a prospective and cross-sectional study of 92 patients with mild AD and of 68 healthy controls from our Department of Neurology. The diagnostic properties of the following tests were compared: Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination III (ACE-III), Memory Impairment Screen (MIS), Montreal Cognitive Assessment (MoCA), and Rowland Universal Dementia Assessment Scale (RUDAS). Results: All tests yielded high diagnostic accuracy, with the ACE-III achieving the best diagnostic properties. The area under the curve was 0.897 for the ACE-III, 0.889 for the RUDAS, 0.874 for the MMSE, 0.866 for the MIS, and 0.856 for the MoCA. The Mini-ACE score from the ACE-III showed the highest diagnostic capacity (area under the curve 0.939). Memory scores of the ACE-III and of the RUDAS showed a better diagnostic accuracy than those of the MMSE and of the MoCA. All tests, especially the ACE-III, conveyed a higher diagnostic accuracy in patients with full primary education than in the less educated group. Implementing normative data improved the diagnostic accuracy of the ACE-III but not that of the other tests. Conclusions: The ACE-III achieved the highest diagnostic accuracy. This better discrimination was more evident in the more educated group.

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Novel serologic biomarkers provide accurate estimates of recentPlasmodium falciparumexposure for individuals and communities

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1501705112 ◽

2015 ◽

Vol 112 (32) ◽

pp. E4438-E4447 ◽

Cited By ~ 100

Author(s):

Danica A. Helb ◽

Kevin K. A. Tetteh ◽

Philip L. Felgner ◽

Jeff Skinner ◽

Alan Hubbard ◽

...

Keyword(s):

Malaria Control ◽

Malaria Incidence ◽

Low Cost ◽

Protein Microarray ◽

Area Under The Curve ◽

Antibody Responses ◽

Selection Strategy ◽

Small Subset ◽

Cross Sectional ◽

Epidemiologic Surveillance

Tools to reliably measurePlasmodium falciparum(Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals.Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates ofPfexposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856Pfantigens by protein microarray in 186 Ugandan children, for whom detailedPfexposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual’s recent exposure. Responses to three novelPfantigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86–0.93), whereas responses to six antigens accurately estimated an individual’s malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.

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King-Devick Sensitivity and Specificity to Concussion in Collegiate Athletes

Journal of Athletic Training ◽

10.4085/1062-6050-0063.21 ◽

2021 ◽

Author(s):

Rachel K. Le ◽

Justus D. Ortega ◽

Sara P. D. Chrisman ◽

Anthony P. Kontos ◽

Thomas A. Buckley ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Sensitivity And Specificity ◽

Area Under The Curve ◽

Collegiate Athletes ◽

Return To Play ◽

Cutoff Score ◽

Confounding Factors ◽

Post Injury ◽

Cross Sectional ◽

Cutoff Scores

Context: The King-Devick (K-D) is used to identify oculomotor impairment following concussion. However, the diagnostic accuracy of the K-D over time has not been evaluated. Objective: (a) Examine the sensitivity and specificity of the K-D test at 0–6 hours of injury, 24–48 hours, asymptomatic, return-to-play, and 6-months following concussion and (b) compare outcomes for differentiating athletes with a concussion from non-concussed across confounding factors (sex, age, contact level, school year, learning disorder, ADHD, concussion history, migraine history, administration mode). Design: Retrospective, cross-sectional design. Setting: Multisite institutions within the Concussion Assessment, Research, and Education (CARE) Consortium. Patients or Other Participants: 1239 total collegiate athletes without a concussion (age=20.31±1.18, male=52.2%) were compared to 320 athletes with a concussion (age=19.80±1.41, male=51.3%). Main Outcome Measure(s): We calculated K-D time difference (sec) by subtracting baseline from the most recent time. Receiver operator characteristics (ROC) and area under the curve (AUC) analyses were used to determine the diagnostic accuracy across timepoints. We identified cutoff scores and corresponding specificity at 80% and 70% sensitivity levels. We repeated ROC with AUC outcomes by confounding factors. Results: King-Devick predicted positive results at 0-6 hours (AUC=0.724, p<0.001), 24-48 hours (AUC=0.701, p<0.001), return-to-play (AUC=0.640, P<0.001), and 6-months (AUC=0.615, P<0.001), but not at asymptomatic (AUC=0.513, P=0.497). The 0–6 and 24–48-hour timepoints yielded an 80% sensitivity cutoff score of −2.6 and −3.2 seconds (faster) respectively, but 46% and 41% specificity. The K-D test had significantly better AUC when administered on an iPad (AUC=0.800, 95%CI:0.747,0.854) compared to the spiral card system (AUC=0.646, 95%CI:0.600,0.692; p<0.001). Conclusions: The K-D test has the greatest diagnostic accuracy at 0–6 and 24–48 hours of concussion, but declines across subsequent post-injury timepoints. AUCs did not significantly differentiate between groups for confounding factors. Our negative cutoff scores indicate that practice effects contribute to improved performance, requiring athletes to outperform their baseline.

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Corrected ESR/Albumin Ratio as a Simple, Practical Marker Predicts the Severity in Egyptian Ulcerative Colitis Patients

The Open Biomarkers Journal ◽

10.2174/1875318302111010008 ◽

2021 ◽

Vol 11 (1) ◽

pp. 8-16

Author(s):

Shimaa El Sharawy ◽

Hemat El-Horany ◽

Ibrahim Amer

Keyword(s):

Ulcerative Colitis ◽

Sensitivity And Specificity ◽

Area Under The Curve ◽

High Sensitivity ◽

Clinical Activity ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Predictive Values ◽

Albumin Ratio ◽

Egyptian Patients

Background: Serum biomarkers are commonly used for diagnosing and monitoring the disease activity of Ulcerative Colitis (UC) patients. However, their role in predicting disease severity among Egyptian patients is unknown. Objectives: The aim of this study was to correlate these biomarkers with clinical, endoscopic and histologic severity. Methods: This is a cross-sectional survey where 55 patients with UC were included to measure corrected Erythrocyte Sedimentation Rate (ESR), hematocrit (Hct), corrected ESR/albumin ratio and albumin, as well as colonoscopy and biopsy. Sensitivity and specificity, positive and negative predictive values were correlated with clinical, endoscopic, histologic severity. Results: The mean age of patients was 33 ± 8.4 years. In total, 27 (49.1%) were males and 28 (50.9%) were females. Area Under the Curve (AUC) values for the diagnosis of severe clinical disease were 0.947, 0.932, 0.727 and 0.685 for corrected ESR/albumin ratio, corrected ESR, Hct and albumin, respectively. Cut-off value to determine endoscopic severity for Hct was 34 (sensitivity: 88.89%, specificity: 83.78%, PPV: 72.7%, NPV: 93.9%, AUC: 0.963, p<0.001). Conclusion: Corrected ESR/albumin ratio was the best predictor of severe clinical activity of UC disease. Hct may be a marker of endoscopic and histological severity due to its high sensitivity and specificity as a diagnostic test.

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Sensitivity And Specificity Of Crandal And Ilayperuma’s Formula To Predict Adult Weight And Height

Dunia Keperawatan ◽

10.20527/dk.v9i1.10261 ◽

2021 ◽

Vol 9 (1) ◽

pp. 107

Author(s):

Dendy Kharisna ◽

Wardah Wardah ◽

Rizka Febtrina

Keyword(s):

Sensitivity And Specificity ◽

Body Height ◽

Area Under The Curve ◽

Upper Arm ◽

Cross Sectional ◽

Adult Weight ◽

Regression Test ◽

Diagnostic Power ◽

Cross Sectional Design ◽

Logistic Regression Test

Many medical conditions do not allow direct weighing or measurement of body height. The circumference of the upper arm (CUA) is an alternative in determining body weight, while the ulna length can be used as an alternative for height. The aim of this study was to identify the sensitivity and specificity of Crandal and Ilayperuma’s Formula to predict adult weight and height in Indonesia, especially in Pekanbaru. This study conducted using a quantitative approach with cross sectional design and involving 116 respondents who recruited using accidental sampling. The instrument used is a questionnaire, manual weight scales, metlin, and heel microtoise. Data were analyzed using spearman to aand logistic regression test. The results showed that the sensitivity value of the Crandal and Ilayperuma’s formula were 78,2% and 63,4%. Meanwhile, the specificity value of Crandal and Ilayperuma’s formula were 75,4% and 80%. The Area Under the Curve (AUC) values in the Crandal and Ilayperuma formulas were 76,7% and 70,7%. Based on these findings, it can be concluded that the Crandal and Ilayperuma’s formula can be used as an alternative in determining the estimation of weight and height of adults in Indonesia, even with moderate diagnostic power.

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Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer disease

Neurology ◽

10.1212/wnl.0000000000010131 ◽

2020 ◽

Vol 95 (8) ◽

pp. e953-e961 ◽

Cited By ~ 4

Author(s):

Marion Tible ◽

Åsa Sandelius ◽

Kina Höglund ◽

Ann Brinkmalm ◽

Emmanuel Cognat ◽

...

Keyword(s):

Alzheimer Disease ◽

Area Under The Curve ◽

The Other ◽

Csf Biomarkers ◽

Discriminative Power ◽

Cross Sectional ◽

Synaptotagmin 1 ◽

Csf Levels ◽

Neurocognitive Decline

ObjectiveTo assess the ability of a combination of synaptic CSF biomarkers to separate Alzheimer disease (AD) and non-AD disorders and to help in the differential diagnosis between neurocognitive diseases.MethodsThis was a retrospective cross-sectional monocentric study. All participants explored with CSF assessments for neurocognitive decline were invited to participate. After complete clinical and imaging evaluations, 243 patients were included. CSF synaptic (GAP-43, neurogranin, SNAP-25 total, SNAP-25aa40, synaptotagmin-1) and AD biomarkers were blindly quantified with ELISA or mass spectrometry. Statistical analysis compared CSF levels between the various groups of AD dementias (n = 81), mild cognitive impairment (MCI)–AD (n = 30), other MCI (n = 49), other dementias (OD) (n = 49), and neurologic controls (n = 35) and their discriminatory powers.ResultsAll synaptic biomarkers were significantly increased in patients with MCI-AD and AD-dementia compared to the other groups. All synaptic biomarkers could efficiently discriminate AD dementias from OD (AUC ≥0.80). All but synaptotagmin were also able to discriminate patients with MCI-AD from controls (area under the curve [AUC] ≥0.85) and those with AD dementias from controls (AUC ≥0.80). Overall, CSF SNAP-25aa40 had the highest discriminative power (AUC 0.93 between patients with AD dementias and controls or OD, AUC 0.90 between those with MCI-AD and controls). Higher levels were associated with 2 alleles of APOE ε4.ConclusionAll synaptic biomarkers tested had a good discriminatory power to distinguish patients with AD abnormal CSF from those with non-AD disorders. SNAP25aa40 demonstrated the highest power to discriminate AD CSF-positive patients from patients without AD and neurologic controls in this cohort.Classification of evidenceThis retrospective study provides Class II evidence that CSF synaptic biomarkers discriminate patients with AD from those without AD.

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Development of ADAF screening tool for emotional and coping problems in cancer patients

10.1101/2021.01.26.21250516 ◽

2021 ◽

Author(s):

Pedro Pérez-Segura ◽

Santos Enrech Francés ◽

Ignacio Juez Martel ◽

Maria Angeles Pérez Escutia ◽

Elena Hernández Agudo ◽

...

Keyword(s):

Cancer Patients ◽

Sensitivity And Specificity ◽

Intraclass Correlation ◽

Area Under The Curve ◽

Correlation Coefficients ◽

P Value ◽

Avoidance Coping ◽

Cross Sectional ◽

And Coping ◽

Anxiety Depression

ABSTRACTPurposePsychological screening in patient with cancer is recommended by clinical guidelines, however most of scales have large number of items, difficulty detection and refer from routine consultations. The specific objective of the study was to develop and validate the ADAF screening for anxiety, depression and coping.Methods/PatientsCross-sectional, multicenter study performed in the medical and radiotherapy oncology services of 5 hospitals in Madrid, coordinated by the Medical Oncology Service of the Hospital Clínico San Carlos (CEIC nº19 / 265-E). To determine the psychometric properties, the ADAF screening questionnaire ADAF was administered, including 5 items (one related to anxiety symptoms, two related to depressive symptoms, one for helplessness coping and one for avoidance coping), and as a gold-standard the HADS and the MiniMAC. Intraclass correlation coefficients and receiver operating characteristic curves were performed. The p value <0.05 was considered significant.ResultsA total of 186 patients completed the evaluation. The correlation coefficients were significant for all dimensions (Anxiety, Depression, Helplessness coping, and Avoidance Coping), with p <0.001. The statistical analysis of ROC curves suggests that the cut-off point for screening is equivalent to a score > 2 points (3 in the case of depression, having two items), with a sensitivity and specificity between 62 and 90%, depending on the item, and an area under the curve above 0.8 for the first 4 items.ConclusionsADAF screening has adequate reliability, good sensitivity and specificity. This instrument is useful and easy to use to identify emotional and coping problems in cancer patients.

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