EE score: an index for simple differentiation of homozygous hemoglobin E and hemoglobin E-β0-thalassemia

2018 ◽  
Vol 56 (9) ◽  
pp. 1507-1513 ◽  
Author(s):  
Kritsada Singha ◽  
Goonnapa Fucharoen ◽  
Kanokwan Sanchaisuriya ◽  
Supan Fucharoen
Keyword(s):  
Predictive Value ◽  
Dna Analysis ◽  
Screening Program ◽  
Inverse Correlation ◽  
Molecular Testing ◽  
Related Disorder ◽  
Hemoglobin E ◽  
Dna Analyses ◽  
Homozygous Hemoglobin E ◽  
Thalassemia Screening

Abstract Background: The objective of the study was to describe a formula based on hemoglobin (Hb)A2 and HbF levels for differentiation of homozygous HbE and HbE-β-thalassemia. Methods: A total of 1256 subjects suspected for homozygous HbE or HbE-β0-thalassemia were recruited at the ongoing thalassemia screening program at Khon Kaen University, Thailand. Hb analysis was done using capillary electrophoresis. Genotyping was based on DNA analysis. An arbitrary formula based on HbA2 and HbF was developed statistically for differentiation of the two conditions. Validation was carried out prospectively on another 139 subjects encountered at routine laboratory. Results: Among 1256 subjects, Hb and DNA analyses identified cases with homozygous HbE (n=1076, 85.7%), HbE-β0-thalassemia (n=140, 11.1%), HbE-δβ0-thalassemia (n=30, 2.4%) and unknown HbE-related disorder (n=10, 0.8%). An inverse correlation between the amounts of HbA2 and HbF in HbE-β0-thalassemia was observed. With differences in the amounts of HbA2 and HbF between the groups, an arbitrary score (7.3 HbA2+HbF) was developed where score above 60 indicated HbE-β0-thalassemia. Application of this score on another 139 subjects showed accurate prediction of HbE-β0-thalassemia with 100% sensitivity, 96.5% specificity, 85.7% positive predictive value and 100% negative predictive value. Successful application onto couples at risk was demonstrated. Conclusions: An established score should prove useful in the differentiation of homozygous HbE and HbE-β0-thalassemia in routine setting and lead to a significant reduction in number of referring cases for molecular testing.

scholarly journals High Reliability of Neonatal Screening for Congenital Adrenal Hyperplasia in Switzerland

2002 ◽  
Vol 87 (9) ◽  
pp. 4106-4110 ◽  
Author(s):  
Michael Steigert ◽  
Eugen J. Schoenle ◽  
Anna Biason-Lauber ◽  
Toni Torresani
Keyword(s):  
Positive Predictive Value ◽  
Congenital Adrenal Hyperplasia ◽  
Predictive Value ◽  
Neonatal Screening ◽  
Screening Program ◽  
High Reliability ◽  
Dried Blood Spots ◽  
Recall Rate ◽  
Adrenal Hyperplasia ◽  
Salt Wasting

Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the sometimes difficult clinical diagnosis and the risks associated with missed diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland, nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried blood spots was introduced in 1992. At the Zurich University Children’s Hospital, 50% of the population of Switzerland is screened. The aim of the study was to evaluate the efficiency of the Zurich screening program. Between January 1, 1993, and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity, 97%). A recall for suspected CAH was performed in only 60 cases, corresponding to a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from screening, as CAH had not been recognized clinically. The timely availability of screening results made therapy possible within the first week of life in most cases and helped in preventing salt-wasting crisis in all patients. With a sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of 50%, the Zurich neonatal screening program for CAH can be considered highly reliable.

scholarly journals Accuracy of Visual Tests for Primary Cervical Cancer Screening in Rural Nepal

2018 ◽  
Vol 56 (214) ◽  
pp. 917-923
Author(s):  
Niresh Thapa ◽  
Muna Maharjan ◽  
Girishma Shrestha ◽  
Narayani Maharjan ◽  
Deborah Lindell ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Screening ◽  
Negative Predictive Value ◽  
Cervical Cancer Screening ◽  
Predictive Value ◽  
Odds Ratio ◽  
Screening Program ◽  
Diagnostic Odds Ratio ◽  
Screening Tests ◽  
Resource Setting

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.

scholarly journals Development and Evaluation of a Novel Fast Broad-Range ITS/LSU DNA PCR and Sequencing Assay (FBR-PCR/S) for Rapid Diagnosis of Invasive Fungal Diseases: Multi-Year Experience in a Large Canadian Healthcare Zone and a Literature Review

2021 ◽  
Author(s):  
B Chow ◽  
M Groeschel ◽  
J Carson ◽  
Thomas Griener ◽  
Deirdre Church
Keyword(s):  
Predictive Value ◽  
Patient Characteristics ◽  
Invasive Fungal Disease ◽  
Molecular Testing ◽  
Fungal Culture ◽  
Diagnostic Efficiency ◽  
Molecular Assay ◽  
Risk Patients ◽  
Sensitivity Specificity ◽  
Canadian Healthcare

Abstract BackgroundThis study evaluated the performance of a novel fast broad range PCR and sequencing (FBR-PCR/S) assay for the improved diagnosis of invasive fungal disease (IFD) in high-risk patients in a large Canadian healthcare region.MethodsA total of 114 clinical specimens (CS) including bronchoalveolar lavages (BALs) were prospectively tested from 107 patients over a 2-year period. Contrived BALs (n=33) inoculated with known fungi pathogens were also tested to increase diversity. Patient characteristics, fungal stain and culture results were collected from the laboratory information system. Dual-priming oligonucleotide (DPO) primers targeted to the ITS (~350 bp) and LSU (~550 bp) gene regions were used to perform FBR-PCR/S assays on extracted BALs/CS. The performance of the molecular test was evaluated against results of fungal stains and culture, and where available, histopathology, and clinical review for the presence of IFD.ResultsThe 107 patients were predominantly male (67, 62.6%%) with a mean age of 59 yrs. (range = 0 to 85 yrs.): 74 (69.2%) patients had at least one underlying comorbidity: 19 (34.5%) had confirmed and 12 (21.8%) had probable IFD. Culture recovered 66 fungal isolates from 55 BALs/CS with Candida spp. and Aspergillus spp. being most common. For BALs, the molecular assay vs. fungal culture had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and efficiency of 88.5% vs.100%, 100% vs. 61.1%, 100% vs. 88.5%, 61.1% vs. 100%, and 90.2% for both. For other CS, the molecular assay had similar performance to fungal culture with sensitivity, specificity, PPV, NPV and efficiency of 66.7%, 87.0%, 66.7%, 87.0% and 81.3% for both methods. Both methods also performed similarly, regardless of whether CS stain/microscopy showed yeast/fungal elements. FBR-PCR/S assays results were reported in ~8h compared to fungal cultures that took between 4 to 6 weeks.ConclusionsRapid molecular testing compared to culture has equivalent diagnostic efficiency but improves clinical utility by reporting a rapid species-level identification the same dayshift (~8h).

scholarly journals Clinical, Biochemical and Molecular Profile of Variant Galactosemia in Children Detected by National Newborn Screening: A Pilot Study

2017 ◽  
Vol 51 (3) ◽  
Author(s):  
Sylvia Capistrano-Estrada ◽  
Daffodil M. Canson ◽  
Catherine Lynn T. Silao
Keyword(s):  
Newborn Screening ◽  
Screening Program ◽  
Molecular Profile ◽  
Molecular Characteristics ◽  
Molecular Testing ◽  
Variant Form ◽  
Limited Information ◽  
Coding Region ◽  
Total Blood ◽  
Galt Activity

Objective. The observed irregularities in the biochemical profile and the limited information on long-term outcomes among patients with Duarte variant (D/G) galactosemia have led to patient management variability. This study examined the molecular characteristics of Filipino patients with presumed variant galactosemia for confirmation of diagnosis. It also aimed to describe the corresponding biochemical, clinical and neurodevelopmental profiles in order to gain a better understanding of the patients with normal galactose metabolites in spite of low to absent GALT activity detected by the local newborn screening program. Methods. Thirteen (13) patients who were presumed to have a variant form of galactosemia by national newborn screening between 2002 and 2010, and who previously underwent physical and neurodevelopmental assessment were included in the study. Repeat clinical, ophthalmologic and neurodevelopmental evaluations were done upon recruitment of participants. Direct sequence analysis of the coding region of the GALT gene was conducted to determine the patients’ genotypes. Results. None of the patients’ genotypes were consistent with Duarte variant (D/G) galactosemia. Their genotypes reflect the normal total blood galactose levels in patients, but were inconsistent with the absent or trace GALT activity. Conclusion. Molecular testing for the entire cohort of presumed “variant” galactosemia Filipino patients will provide better profiling of this condition. Re-evaluation and assessment of the current guidelines used by national newborn screening in classifying variant galactosemia are recommended.

8. Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in HIV-positive men who have sex with men

Sexual Health ◽  
2013 ◽  
Vol 10 (6) ◽  
pp. 573
Author(s):  
Elena Sendagorta Cudós ◽  
Maria P. Romero Gomez ◽  
Beatriz Hernandez Novoa ◽  
Ander Mayor ◽  
Jose I. Bernardino De La Serna ◽  
...  
Keyword(s):  
Predictive Value ◽  
Screening Program ◽  
University Hospital ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Cross Sectional ◽  
Hpv Dna ◽  
Hpv E6 ◽  
Anal Cytology ◽  
Intraepithelial Lesions

Background Currently, screening for anal high-grade squamous intraepithelial lesions (HSIL) relies on anal cytology and high-resolution anoscopy (HRA). Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM HIV-infected patients, in comparison to DNA-HR-HPV and anal cytology. Methods: This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, HRA and histology were analysed. HR-HPV-DNA detection was performed by means of the CLART HPV2 assay (GENOMICA SAU.). E6/E7-mRNA detection of HR-HPV types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy l’Etoile, France). Results: HR-HPV DNA and HPV E6/E7 mRNA were detected in 82% and 57% of the anal smears, respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared with 97.9%, 31.5%, 55.4% and 94.4%, respectively, for HR-HPV DNA testing and 83%, 40.7%, 54.9%, 73.3%, respectively, for cytology testing. Conclusions: In comparison with the other tests, the NucliSENS EasyQ HPV assay yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM HIV-infected patients.

35. Accuracy of anal cytology in predicting histological HSIL: baseline results from the Australian Study of the Prevention of Anal Cancer (SPANC)

Sexual Health ◽  
2013 ◽  
Vol 10 (6) ◽  
pp. 587
Author(s):  
Jennifer Roberts ◽  
Clare Biro ◽  
Annabelle Farnsworth ◽  
Debbie Ekman ◽  
Marjorie Adams ◽  
...  
Keyword(s):  
Predictive Value ◽  
Screening Program ◽  
Anal Carcinoma ◽  
Hiv Positive ◽  
Homosexual Men ◽  
Significant Difference ◽  
Anal Cytology ◽  
Cytological Abnormality ◽  
Sensitivity Specificity ◽  
The Bethesda System

Background Anal cytology may form the basis of a future screening program to prevent anal carcinoma. Therefore, the accuracy of anal Papanicolaou tests in detecting histological HSIL needs to be evaluated. Methods: SPANC is a 3-year prospective study in homosexual men aged ≥35 years. At each of five visits, men undergo collection of a ThinPrep® anal cytological sample, high-resolution anoscopy (HRA) and biopsy of any abnormalities. Cytology is reported using the Bethesda system. Histology is reported using lower anogenital squamous terminology. Results: 351 men had a baseline visit by end July 2013. Median age was 49 (range: 35–79) years and 101 (28.8%) men were HIV positive. Anal cytology results were: unsatisfactory in 21 (6.0%), negative in 143 (40.7%), ASC-US in 51 (14.5%), LSIL in 22 (6.3%), ASC-H in 45 (12.8%) and HSIL in 69 (19.7%). 293 of 351 (83.5%) men had baseline histology. The most severe abnormality for each was: negative for SIL in 98 (33.4%), LSIL in 87 (29.7%) and HSIL in 108 (36.9%). Anal cytology sensitivity for histological HSIL (at ASC-US threshold) was 79.0%. Specificity was 53.8%. Positive predictive value (PPV) of any cytological abnormality for histological HSIL was 44.4% and PPV of HSIL cytoprediction was 63.8%. Negative predictive value (NPV) was 84.6%. Overall there was no significant difference between HIV positive and negative men with respect to sensitivity, specificity, PPV or NPV. Conclusions: These results indicate that histological HSIL is common in homosexual men. The finding of any cytological abnormality should prompt HRA. However, both cytology and HRA can miss or underestimate significant lesions in a single screening.

scholarly journals Evaluation of Omics-Based Strategies for the Management of Advanced Lung Cancer

2020 ◽  
pp. OP.20.00117
Author(s):  
Ravi Salgia ◽  
Isa Mambetsariev ◽  
Rebecca Pharaon ◽  
Jeremy Fricke ◽  
Angel Ray Baroz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Decision Making ◽  
Targeted Therapy ◽  
Predictive Value ◽  
Advanced Nsclc ◽  
Therapeutic Options ◽  
Advanced Lung Cancer ◽  
Molecular Testing ◽  
Cox Regression Analysis ◽  
The Impact

PURPOSE: Omic-informed therapy is being used more frequently for patients with non–small-cell lung cancer (NSCLC) being treated on the basis of evidence-based decision-making. However, there is a lack of a standardized framework to evaluate those decisions and understand the association between omics-based management strategies and survival among patients. Therefore, we compared outcomes between patients with lung adenocarcinoma who received omics-driven targeted therapy versus patients who received standard therapeutic options. PATIENTS AND METHODS: This was a retrospective study of patients with advanced NSCLC adenocarcinoma (N = 798) at City of Hope who received genomic sequencing at the behest of their treating oncologists. A thoracic oncology registry was used as a clinicogenomic database to track patient outcomes. RESULTS: Of 798 individuals with advanced NSCLC (median age, 65 years [range, 22-99 years]; 60% white; 50% with a history of smoking), 662 patients (83%) had molecular testing and 439 (55%) received targeted therapy on the basis of the omic-data. A fast-and-frugal decision tree (FFT) model was developed to evaluate the impact of omics-based strategy on decision-making, progression-free survival (PFS), and overall survival (OS). We calculated that the overall positive predictive value of the entire FFT strategy for predicting decisions regarding the use of tyrosine kinase inhibitor–based targeted therapy was 88% and the negative predictive value was 96%. In an adjusted Cox regression analysis, there was a significant correlation with survival benefit with the FFT omics-driven therapeutic strategy for both PFS (hazard ratio [HR], 0.56; 95% CI, 0.42 to 0.74; P < .001) and OS (HR, 0.51; 95% CI, 0.36 to 0.71; P < .001) as compared with standard therapeutic options. CONCLUSION: Among patients with advanced NSCLC who received care in the academic oncology setting, omics-driven therapy decisions directly informed treatment in patients and was correlated with better OS and PFS.

Genetic epidemiology of beta-thalassemia in the Maldives: 23 years of a beta-thalassemia screening program

Gene ◽  
2020 ◽  
Vol 741 ◽  
pp. 144544
Author(s):  
Ibrahim Mustafa ◽  
Naila Firdous ◽  
Fatma M. Shebl ◽  
Zumin Shi ◽  
Mariya Saeed ◽  
...  
Keyword(s):  
Genetic Epidemiology ◽  
Screening Program ◽  
Beta Thalassemia ◽  
Thalassemia Screening

scholarly journals MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-β-THALASSEMIA DISEASE WITHOUT α--THALASSEMIA

2019 ◽  
Vol 11 (1) ◽  
pp. e2019038 ◽  
Author(s):  
Paramee Phanrahan ◽  
Supawadee Yamsri ◽  
Nattiya Teawtrakul ◽  
Goonnapa Fucharoen ◽  
Kanokwan Sanchaisuriya ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Globin Gene ◽  
Phenotypic Expression ◽  
Nucleotide Polymorphisms ◽  
Thalassemia Patient ◽  
Hemoglobin E ◽  
Modifying Factors ◽  
Myb Gene ◽  
Hb E ◽  
Klf1 Gene

Background: The finding of many Thai Hb E-β0-thalassemia patients with non-transfusion dependent thalassemia (NTDT) phenotype without co-inheritance of α-thalassemia has prompted us to investigate the existence of other genetic modifying factors. Methods: Study was done on 146 adult Thai patients with NTDT Hb E-β0-thalassemia and a homozygous β-thalassemia patient without co-inheritance of α-thalassemia. Multiple single-nucleotide polymorphisms (SNPs) associated with γ-globin gene expression including the Gγ-XmnI of HBG2 gene, rs2297339, rs4895441, and rs9399137 of the HBS1L-MYB gene, rs4671393 in the BCL11A gene, and G176AfsX179, T334R, R238H and -154 (C-T) in the KLF1 gene were investigated using PCR-and related techniques. Results: Heterozygous and homozygous for Gg-XmnI of HBG2 gene were detected at 68.0% and 6.1%, respectively. Further DNA analysis identified the rs2297339 (C-T), rs4895441 (A-G), and rs9399137 (T-C) of HBS1L-MYB gene in 86.4%, 22.5% and 20.4%, respectively. The rs4671393 (G-A) of the BCL11A gene was found at 31.3%. For the KLF1 gene, the T334R and G176AfsX179 (+/-) were detected at 8.2% and 1.4%, respectively. Conclusion: It was found that these SNPs when analyzed in combination could explain the mild phenotypic expression of all cases. These results underline the importance of these informative SNPs on phenotypic expression of Hb E-β-thalassemia patients.

Sporadic vestibular schwannoma: a molecular testing summary

2020 ◽  
pp. jmedgenet-2020-107022
Author(s):  
Katherine V Sadler ◽  
Naomi L Bowers ◽  
Claire Hartley ◽  
Philip T Smith ◽  
Simon Tobi ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Vestibular Schwannoma ◽  
Dna Analysis ◽  
Genomic Medicine ◽  
Familial Risk ◽  
Neurofibromatosis Type ◽  
Molecular Testing ◽  
Pathogenic Variants ◽  
Patient Subgroups

ObjectivesCases of sporadic vestibular schwannoma (sVS) have a low rate of association with germline pathogenic variants. However, some individuals with sVS can represent undetected cases of neurofibromatosis type 2 (NF2) or schwannomatosis. Earlier identification of patients with these syndromes can facilitate more accurate familial risk prediction and prognosis.MethodsCases of sVS were ascertained from a local register at the Manchester Centre for Genomic Medicine. Genetic analysis was conducted in NF2 on blood samples for all patients, and tumour DNA samples when available. LZTR1 and SMARCB1 screening was also performed in patient subgroups.ResultsAge at genetic testing for vestibular schwannoma (VS) presentation was younger in comparison with previous literature, a bias resulting from updated genetic testing recommendations. Mosaic or constitutional germline NF2 variants were confirmed in 2% of patients. Pathogenic germline variants in LZTR1 were found in 3% of all tested patients, with a higher rate of 5% in patients <30 years. No pathogenic SMARCB1 variants were identified within the cohort. Considering all individuals who received tumour DNA analysis, 69% of patients were found to possess two somatic pathogenic NF2 variants, including those with germline LZTR1 pathogenic variants.ConclusionsUndiagnosed schwannoma predisposition may account for a significant minority of apparently sVS cases, especially at lower presentation ages. Loss of NF2 function is a common event in VS tumours and may represent a targetable common pathway in VS tumourigenesis. These data also support the multi-hit mechanism of LZTR1-associated VS tumourigenesis.

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