scholarly journals Assessment of Screening Approach in Early and Differential Alzheimer’s Disease Diagnosis

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1662
Author(s):  
Laura Ferré-González ◽  
Carmen Peña-Bautista ◽  
Lourdes Álvarez-Sánchez ◽  
Inés Ferrer-Cairols ◽  
Miguel Baquero ◽  
...  

Background: Alzheimer’s disease (AD) is the leading cause of dementia in the elderly population. Currently, diagnosis is based on invasive and expensive techniques, so there is a growing need to look for other possible tests, as well as carry out clinical validation. Studies from the literature showed potential diagnosis models, including some AD risk factors (age, gender, ApoE-ε4 genotype) and other variables (biomarkers levels, neuroimaging). Specifically, a recent model was performed from lipid peroxidation compounds in plasma samples to identify patients with early AD. However, there is a lack of studies about clinical validation of these preliminary diagnosis models. Methods: Plasma samples from participants classified into AD (n = 61), non-AD (n = 17), and healthy (n = 44) were analyzed. In fact, lipid peroxidation compounds were determined by liquid chromatography and mass spectrometry. Then, a previously developed diagnosis model was clinically validated, evaluating some diagnosis indexes. Results: The validation of the preliminary diagnosis model showed satisfactory diagnosis indexes (accuracy 77%, sensitivity 89%, specificity 61%, diagnostic odds ratio 12.5, positive predictive value 76%). Next, a useful screening tool, including the ApoE genotype, was developed, identifying patients with a higher risk of developing AD and improving the corresponding diagnosis indexes (accuracy 82%, sensitivity 81%, specificity 85%, diagnostic odds ratio 23.2, positive predictive value 90.5%). Conclusion: A new screening approach could improve the early, minimally invasive, and differential AD diagnosis in the general population.

2018 ◽  
Vol 56 (214) ◽  
pp. 917-923
Author(s):  
Niresh Thapa ◽  
Muna Maharjan ◽  
Girishma Shrestha ◽  
Narayani Maharjan ◽  
Deborah Lindell ◽  
...  

Introduction: In Nepal, cervical cancer is the most common female cancer. Unfortunately, there is no uniform effective screening system available all around the country. The objective of this study is to evaluate the cytology, Visual Inspection with Acetic Acid and with Lugol’s Iodine alone or in combination to detect a pre-cancerous lesion in rural Nepal.Methods: It is an analytical cross-sectional study. Convenience sampling technique was used to select participants who were apparently healthy, married, non- pregnant women of aged 20-65 years for cervical cancer screening program. Screening tests were performed on all eligible women (n=2143) after socio-demographic and reproductive health data collection. A biopsy was applied as a gold standard test. Cross-tabulations were used to describe the test sensitivity, specificity, positive predictive value, and negative predictive value at a 95% confidence interval. Diagnostic odds ratio was also calculated. Results: A majority, 2143 (94%), of women accepted and participated in this study. The sensitivity vs specificity of cytology, VIA, and VILI was 57.1% vs 98.3%, 71.4% vs 88.8% and 78.6% vs 85.1%, and of the co-testing of ‘Both positive VIA and VILI’ and ‘Either positive VIA or VILI’ was 64.3% vs 85.7% and 90.1% vs 83.7% respectively. Negative predictive value of all tests exceeded 99.7%. Cytology had the highest Diagnostic odds ratio (64.9), followed by the co-test ‘Either positive VIA or VILI’ (27.7).Conclusions: Cervical cancer screening by co-testing ‘Either positive VIA or VILI’ is more useful than cytology; VIA and or VILI are easy, safe, feasible and well-accepted tests in a low resource setting, Nepal.


Author(s):  
Zirui Meng ◽  
Minjin Wang ◽  
Huan Song ◽  
Shuo Guo ◽  
Yanbing Zhou ◽  
...  

ABSTRACTBackgroundCOVID-19 has been spreading globally since emergence, but the diagnostic resources are relatively insufficient.ResultsIn order to effectively relieve the resource deficiency of diagnosing COVID-19, we developed a machine learning-based diagnosis model on basis of laboratory examinations indicators from a total of 620 samples, and subsequently implemented it as a COVID-19 diagnosis aid APP to facilitate promotion.ConclusionsExternal validation showed satisfiable model prediction performance (i.e., the positive predictive value and negative predictive value was 86.35% and 84.62%, respectively), which guarantees the promising use of this tool for extensive screening.


2019 ◽  
pp. 1-15 ◽  
Author(s):  
Michael A. Pritchett ◽  
D. Ross Camidge ◽  
Manu Patel ◽  
Jamil Khatri ◽  
Steven Boniol ◽  
...  

PURPOSE Guidelines advocate molecular profiling in the evaluation of advanced non–small-cell lung cancer (NSCLC) and support the use of plasma circulating tumor DNA (ctDNA)-based profiling for patients with insufficient tissue. Thorough prospective clinical validation studies of next-generation sequencing (NGS)-based ctDNA assays are lacking. We report the multicentered prospective clinical validation of the InVision ctDNA assay in patients with advanced untreated NSCLC. METHODS A total of 264 patients with untreated advanced NSCLC were prospectively recruited, and their plasma was analyzed using a ctDNA NGS assay for detection of genomic alterations in 36 commonly mutated genes. Tumor tissue was available in 178 patients for molecular profiling for comparison with plasma profiling. The remaining 86 patients were included to compare ctDNA profiles in patients with and without tissue for profiling. RESULTS Concordance of InVisionFirst with matched tissue profiling was 97.8%, with 82.9% positive predictive value, 98.5% negative predictive value, 70.6% sensitivity, and 99.2% specificity. Considering specific alterations in eight genes that most influence patient management, the positive predictive value was 97.8%, with 97.1% negative predictive value, 73.9% sensitivity, and 99.8% specificity. Across the entire study, 48 patients with actionable alterations were identified by ctDNA testing compared with only 38 by tissue testing. ctDNA NGS reported either an actionable alteration or an alteration generally considered mutually exclusive for such actionable changes in 53% of patients. CONCLUSION The liquid biopsy NGS assay demonstrated excellent concordance with tissue profiling in this multicenter, prospective, clinical validation study, with sensitivity and specificity equivalent to Food and Drug Administration–approved single-gene ctDNA assays. The use of plasma-based molecular profiling using NGS led to the detection of 26% more actionable alterations compared with standard-of-care tissue testing in this study.


Author(s):  
Jian Fu ◽  
Xu Zhou ◽  
Liang Chen ◽  
Sheng Lu

Background: Acute appendicitis (AA) is a common cause for abdominal pain encountering unnecessary surgeries in emergency departments. The present meta-analysis aims to assess the accuracy of abdominal ultrasound in suspected acute appendicitis cases in terms of sensitivity, specificity, and post-test odds for positive and negative results. Materials and Methods: An extensive and systematic search was conducted in Medline (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 2010 till the end of March 2021. Two authors analyzed studies for inclusion, collected results, and conducted analyses separately. The histopathological study on tissue collected during appendectomy served as the gold standard for determining the final diagnosis. The accuracy was determined by evaluating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio. Results: Out of 3193 references, a total of 18 studies were selected. Overall sensitivity of 77.2% (95 % CI – 75.4 – 78.9%) and specificity of 60% (95 % CI – 58% – 62%) were observed. The diagnostic odds ratio of 6.88(95 % CI 1.99 – 23.82) was obtained. Conclusion: Abdominal ultrasound shows significant accuracy of diagnosis in patients with suspected acute appendicitis.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jian Fu ◽  
Xu Zhou ◽  
Liang Chen ◽  
Sheng Lu

Background: Acute appendicitis (AA) is a common cause of abdominal pain encountering unnecessary surgeries in emergency departments. The present meta-analysis aims to assess the accuracy of abdominal ultrasound in suspected acute appendicitis cases in terms of sensitivity, specificity, and post-test odds for positive and negative results.Materials and Methods: An extensive and systematic search was conducted in Medline (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 2010 till the end of March 2021. Two authors analyzed studies for inclusion, collected results, and conducted analyses separately. Examination of the histopathological tissue collected during appendectomy served as a gold standard for determining the final diagnosis of appendicitis. The accuracy was determined by evaluating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio.Results: Out of 3,193 references, a total of 18 studies were selected. Overall sensitivity of 77.2% (95% CI – 75.4–78.9%) and specificity of 60% (95% CI – 58–62%) were observed. The diagnostic odds ratio of 6.88(95% CI 1.99–23.82) was obtained.Conclusion: Abdominal ultrasound shows significant accuracy of diagnosis in patients with suspected acute appendicitis.


2020 ◽  
Author(s):  
Ελευθέριος Βαβουλίδης

Σκοπός: Η μεθυλίωση DNA σε περιοχές γονιδιακών υποκινητών έχει παρατηρηθεί σε αρκετά είδη καρκίνων, συμπεριλαμβανομένου και του Καρκίνου του Μαστού. Ένα πρωτόκολλο Methylation Specific PCR (MSP) σχεδιάστηκε και εφαρμόστηκε σε κλινικά δείγματα Αναρρόφησης δια λεπτής βελόνης (Fine Needle Aspiration Biopsy, FNAB) μαστού, ενός βιολογικού υλικού που έχει ελάχιστα χρησιμοποιηθεί στην βιβλιογραφία, για να προσδιοριστούν τα επίπεδα μεθυλίωσης των υποκινητών των γονιδίων CND2, APC, HIN1 & CDH13 και να εκτιμηθεί το κατά πόσο αυτό το πολυγονιδιακό πάνελ μεθυλίωσης μπορεί να χρησιμοποιηθεί ως βιοδείκτης για την ανίχνευση του Καρκίνου του Μαστού σε ελληνικό πληθυσμό. Μέθοδοι: Οι 104 συμμετέχοντες υπεβλήθησαν σε FNAB το υλικό της οποίας εκτιμήθηκε κυτταρολογικά για κακοήθεια μαστού ή μη και χρησιμοποιήθηκε για την περαιτέρω επιγενετική ανάλυση. Έγινε απομόνωση του DNA από τα κλινικά δείγματα FNAB μαστού και στη συνέχεια ακολούθησε η μετατροπή του παρουσία όξινου θειώδους νατρίου (bisulfite conversion). Οι αντιδράσεις MSP έγιναν με εκκινητές (primers) ειδικούς είτε για την μεθυλιωμένη είτε για τη μη μεθυλιωμένη κατάσταση για καθένα από τα 4 υπό μελέτη γονίδια. Τα τελικά MSP-προϊόντα αναλύθηκαν σε 2% πήκτωμα αγαρόζης με ηλεκτροφόρηση. Αποτελέσματα: Υπερμεθυλίωση παρατηρήθηκε στο 74%, 69.2%, 59.6% και 63.4% των δειγμάτων για τα γονίδια CND2, HIN1, APC και CDH13 αντιστοίχως. Το γονίδιο CND2 ήταν το πιο συχνά μεθυλιωμένο στα περιστατικά με κυτταρολογική διάγνωση κακοήθειας (90%) και τα γονίδια APC και HIN1 στα περιστατικά διαγνωσμένα ως ύποπτα για κακοήθεια (88.2%). Σημαντική συσχέτιση παρατηρήθηκε μεταξύ της ιστολογικής διάγνωσης και των συχνοτήτων μεθυλίωσης όλων των γονιδίων μελέτης (p-values<0.001). Βρέθηκε ότι ο σχετικός κίνδυνος (Odds Ratio) για κακοήθεια μαστού ήταν 8.267 για το γονίδιο CND2, 5.235 για το γονίδιο APC, 7.852 για το γονίδιο HIN1 and 22.920 για το γονίδιο CDH13, υποδηλώνοντας την θετική συσχέτιση της μεθυλίωσης των 4 γονιδίων με την εμφάνιση κακοήθειας μαστού. Επίσης, υπολογίστηκαν οι διαγνωστικές παράμετροι για κάθε γονίδιο και τα αποτελέσματα δείχνουν ότι ο συνδυασμός των τεσσάρων γονιδίων σε ένα πολυγονιδιακό πάνελ μεθυλίωσης αυξάνει σημαντικά την Ειδικότητα (Specificity) και Θετική Προγνωστική Αξία (Positive Predictive Value) συγκριτικά με την μεθυλίωση οποιουδήποτε μεμονωμένου εκ των τεσσάρων γονιδίων. Συμπεράσματα: Η μελέτη αυτή δείχνει ότι η FNAB μαστού σε συνδυασμό με τα δεδομένα μεθυλίωσης από τα αναρροφημένα κυτταρολογικά υλικά μαστού εμφανίζουν πολλά υποσχόμενα αποτελέσματα όσον αφορά την χρήση τους ως βιοδείκτη για την πρώιμη ανίχνευση του κινδύνου για Καρκίνο του Μαστού σε γυναίκες με ύποπτες αλλοιώσεις μαστού.


Author(s):  
Pierrick Henneton ◽  
Juliette Albuisson ◽  
Salma Adham ◽  
Anne Legrand ◽  
Jean Michael Mazzella ◽  
...  

Background: Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disease secondary to mutations within the COL3A1 gene. The diagnosis of vascular Ehlers-Danlos syndrome is challenging, and patient selection for genetic testing relies on diagnostic criteria, which have never been evaluated. Methods: All patients seen at a dedicated tertiary referral center for a suspicion of vascular Ehlers-Danlos syndrome between January 2001 and March 2016 were retrospectively included in a diagnostic accuracy study. Major and minor diagnostic criteria of the Villefranche classification were tested for sensitivity, specificity, positive and negative predictive values, according to results of genetic testing. Results: N=519 patients were eligible for analysis dividing into n=384 probands and n=135 relatives. A pathogenic COL3A1 variant was identified in n=165 (31.8%) patients. The Villefranche criteria were met for n=248 patients with a sensitivity of 79% (95% CI, 0.72–0.85) and a negative predictive value of 87% (95% CI, 0.83–0.91). Diagnostic accuracy was highest for symptomatic probands (sensitivity 92%; negative predictive value 95%) with limited specificity (60%). Probands ≤25 years had the worst diagnostic performance. The revised diagnostic Criteria (2017) were less accurate than the Villefranche classification (overall diagnostic odds-ratio, 4.17 versus 7.8; probands diagnostic odds-ratio, 4.04 versus 18.1; and probands ≤25 years diagnostic odds-ratio, 2.36 versus 5.1) mainly due to a lack of sensitivity. Conclusions: The Villefranche criteria provide accurate detection of symptomatic probands in specialized practice but have limited specificity. The revised diagnostic criteria for vascular Ehlers-Danlos syndrome have increased specificity, but its overall performance is poorer. The early clinical diagnosis of probands without family history is not addressed by both diagnostic classifications.


2019 ◽  
Vol 52 (2) ◽  
pp. 104-109
Author(s):  
Ives Alexandre Yutani Koseki ◽  
Matheus Rosso Benedet ◽  
Guilherme De Sá ◽  
Rafael De Conti ◽  
Roberto Meister Bernardi ◽  
...  

Background: Prostate cancer is the second most incident of the male population in Brazil. The aim of this study is to analyze the frequency of risk factors associated to the evolution of the prostate cancer and the impact of conducting examinations in the age range (55-69 years old), in assisting health professionals to manage and prevent the disease. Methods: A case-control study was performed on patients from 2011 to 2016 in Criciúma – SC, Brazil. The sample was divided into two groups, one with biopsy for prostate adenocarcinoma (case; n = 124) and the other with a negative biopsy (control; n = 251). The following variables were compared between the two groups: age, family history of prostate cancer, prostate specific antigen, and altered digital rectal examination. Results: In the case group, ranging between 55-69 years old, there was a significant higher of altered digital rectal examination (p < 0.001, odds ratio 15.5 and positive predictive value 91.3%), prostate-specific antigen ≥ 4 ng/mL (p < 0.001, odds ratio 7.02 and positive predictive value 56.2%) and when both exams were altered (p < 0.001, odds ratio was 19.63 and the positive predictive value was 90.5%). Conclusion: This findings show that, mainly between 55-69 years old, there is a significant correlation between positive biopsy, altered digital rectal examination, and PSA ≥ 4 ng/mL.


Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 649
Author(s):  
Carmen Peña-Bautista ◽  
Lourdes Álvarez ◽  
Thierry Durand ◽  
Claire Vigor ◽  
Ana Cuevas ◽  
...  

Background: Differential diagnosis of Alzheimer’s disease (AD) is a complex task due to the clinical similarity among neurodegenerative diseases. Previous studies showed the role of lipid peroxidation in early AD development. However, the clinical validation of potential specific biomarkers in minimally invasive samples constitutes a great challenge in early AD diagnosis. Methods: Plasma samples from participants classified into AD (n = 138), non-AD (including MCI and other dementias not due to AD) (n = 70) and healthy (n = 50) were analysed. Lipid peroxidation compounds (isoprostanes, isofurans, neuroprostanes, neurofurans) were determined by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Statistical analysis for biomarkers’ clinical validation was based on Elastic Net. Results: A two-step diagnosis model was developed from plasma lipid peroxidation products to diagnose early AD specifically, and a bootstrap validated AUC of 0.74 was obtained. Conclusion: A promising AD differential diagnosis model was developed. It was clinically validated as a screening test. However, further external validation is required before clinical application.


2021 ◽  
Vol 54 (4) ◽  
pp. 225-231
Author(s):  
Francisco de Souza Santos ◽  
Nupur Verma ◽  
Guilherme Watte ◽  
Edson Marchiori ◽  
Tan-Lucien H. Mohammed ◽  
...  

Abstract Objective: To establish the diagnostic performance of diffusion-weighted magnetic resonance imaging (DWI) in discriminating malignant from non-malignant thoracic lymph nodes. Materials and Methods: This was a meta-analysis involving systematic searches of the MEDLINE, EMBASE, and Web of Science databases up through April 2020. Studies reporting thoracic DWI and lymph node evaluation were included. The pooled sensitivity, specificity, diagnostic odds ratio, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated. Results: We evaluated six studies, involving a collective total of 356 mediastinal lymph nodes in 214 patients. Thoracic DWI had a pooled sensitivity and specificity of 92% (95% confidence interval [95% CI]: 71-98%) and 93% (95% CI: 79-98%), respectively. The positive and negative likelihood ratios were 13.2 (95% CI: 4.0-43.8) and 0.09 (95% CI: 0.02-0.36), respectively. The diagnostic odds ratio was 149 (95% CI: 18-1,243), and the AUC was 0.97 (95% CI: 0.95-0.98). Conclusion: DWI is a reproducible technique and has demonstrated high accuracy for differentiating between malignant and benign states in thoracic lymph nodes.


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