International Multi-Site Clinical Validation of Point-of-Care Microchip Electrophoresis Test for Hemoglobin Variant Identification

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3373-3373
Author(s):  
Arwa Fraiwan ◽  
Muhammad Noman Hasan ◽  
Ran An ◽  
Julia Z. Xu ◽  
Amy J. Rezac ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Low Income ◽  
Research Funding ◽  
Point Of Care ◽  
Low Income Countries ◽  
Clinical Validation ◽  
Test Results ◽  
Blood Samples ◽  
Hb E ◽  
Equity Ownership

Introduction: Nearly 24% of the world's population carry hemoglobin (Hb) gene variants, with the large majority of affected births occurring in low-income countries. The most prevalent structural Hb variants are the recessive β-globin gene mutations, βS or S, βC or C, and βE or E1. Hb S mutation is prevalent in sub-Saharan Africa and in Central India. Hb C is common in West Africa, and Hb E is common in Southeast Asia and in India. Homozygotes or compound heterozygotes with βS (e.g., Hb SS or SC) have sickle cell disease (SCD), a chronic sickling disorder associated with pain, chronic multi-organ damage, and high mortality. While Hb EE causes only a mild microcytic anemia, Hb E in combination with β-thalassemia can lead to transfusion dependent thalassemia. Though carriers are typically asymptomatic, they may pass the mutations to their offspring. Screening is needed so that these disorders can be diagnosed early and managed in a timely manner2. For example, in low-income countries, due to lack of nationwide screening and comprehensive care programs, up to 80% of babies born with SCD are undiagnosed and less than half of them survive beyond 5 years of age2. The unmet need for affordable, portable, accurate point-of-care tests to facilitate decentralized hemoglobin testing in resource-constrained countries is well-recognized 2,3. Here, we present international multi-site clinical validation results and high diagnostic accuracy of the 'HemeChip' (Fig. 1), an affordable, 10-minute point-of-care microchip electrophoresis test for identifying common Hb variants S, C, and E. Methods: Institutional Review Board approvals were obtained at each study site, and blood samples were collected as part of the standard clinical care. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. 315 children (6 weeks to 5 years of age) were tested in Kano, Nigeria. Study participants were enrolled at three hospitals, Amino Kano Teaching Hospital, Murtala Mohammed Specialist Hospital, and Hasiya Bayero Pediatric Hospital. 124 subjects (7 weeks to 63 years old) were included in the study at Siriraj Thalassemia Center in Bangkok, Thailand. 298 subjects (8 months to 65 years old) were tested at a referral testing facility of ICMR-National Institute of Research in Tribal Health, located at Late Baliram Kashayap Memorial Medical College, Jagdalpur, Chhattisgarh, India. Blood samples were tested with both HemeChip and the standard reference methods, high performance liquid chromatography or cellulose acetate electrophoresis. Reference test results were not available to the HemeChip users. Similarly, HemeChip test results were not available to the users of the standard reference tests. Clinical validation studies presented here were performed with a fully functional, portable HemeChip prototype developed at Case Western Reserve University (Fig. 1A). A commercial product has been developed based on this technology by Hemex Health Inc. under the product name, GazelleTM(Fig. 1B). Results and Discussion: Among the total 768 tests performed with HemeChip in all test sites, 732 were valid tests, as defined by the Standards for Reporting Diagnostic Accuracy (STARD)4. HemeChip correctly identified all subjects with Hb SS, Hb SC, Hb AS, Hb AE, and Hb EE with 100% accuracy (Table 1). Nine subjects with normal Hb (Hb AA) were identified as HbSS in Nigeria. No subjects with disease were identified as normal or trait by HemeChip. Three subjects with compound heterozygous Hb Sβ-thalassemia (2 subjects with Hb Sβ+-thalassemia, 1 subject with Hb Sβ0-thalassemia) were identified as Hb SS. Sensitivity was 100% for all Hb types tested. Specificity was 98.7% for Hb SS versus other Hb types, and 100% for all other Hb types tested. HemeChip displayed an overall diagnostic accuracy of 98.4% in comparison to standard reference methods for the Hb variants tested in all clinical testing sites (Table 1). HemeChip is a versatile point-of-care system that enables affordable, accurate, decentralized hemoglobin testing in resource-limited settings. References: 1. Weatherall DJ, Clegg JB. Bull World Health Organ. 2001;79(8):704-712. 2. Mburu J, Odame I. International Journal of Laboratory Hematology. 2019;41(S1):82-88. 3. Alapan Y, Fraiwan A, Kucukal E, et al. Expert Review of Medical Devices. 2016;13(12):1073-1093. 4. Bossuyt PM, Reitsma JB, Bruns DE, et al. BMJ : British Medical Journal. 2015;351:h5527. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Piccone:Hemex Health, Inc.: Patents & Royalties. Little:Hemex Health, Inc.: Patents & Royalties; GBT: Research Funding. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

scholarly journals Clinical Testing of Hemechip in Nigeria for Point-of-Care Screening of Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1095-1095 ◽  
Author(s):  
Muhammad Noman Hasan ◽  
Arwa Fraiwan ◽  
Priyaleela Thota ◽  
Tolulope Oginni ◽  
Grace Mfon Olanipekun ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Research Funding ◽  
Point Of Care ◽  
Cost Effective ◽  
Test Results ◽  
Clinical Testing ◽  
Cell Disease ◽  
Blood Samples ◽  
The World ◽  
Hemoglobin Variants

Abstract In sub-Saharan Africa, nearly a quarter of a million babies are born with sickle cell disease (SCD) each year. An estimated 50-90% of these babies die before age 5 due to lack of early diagnosis and timely treatment. The World Health Organization estimates that more than 70% of SCD related deaths are preventable with simple, cost-effective interventions, such as early screening followed by affordable and widely available treatment regimens. Here, we present the early clinical testing results of HemeChip, which is the first single-use cartridge-based microchip electrophoresis hemoglobin screening platform. HemeChip was developed by Hemex Health, Inc., based on technology licensed from Case Western Reserve University. HemeChip allows affordable, objective, quantitative screening of hemoglobin variants at the point-of-care. HemeChip works with a drop of finger or heel-prick blood and separates hemoglobin variants on a piece of cellulose acetate paper that is housed in an injection molded plastic cartridge with a precisely controlled electric field. HemeChip works with a portable reader to produce easily understandable, objective, and quantitative descriptions of the hemoglobin types and percentages present in a blood sample. The HemeChip reader guides the user step-by-step through the test procedure with animated on-screen instructions to minimize user errors. Hemoglobin identification and quantification is automatically done with a custom software on the reader. HemeChip reader records and analyzes the hemoglobin electrophoresis real-time, and it can wirelessly transmit the test results to a central electronic database, if needed. HemeChip prototype units have been clinically tested and benchmarked against the clinical standard technique in Kano, Nigeria, where the SCD prevalence is the highest in the world. We tested a total of 248 subjects (228 children aged 6 weeks to 5 years in Kano, Nigeria; and 20 adults in Cleveland, Ohio, United States) under institutional review board approval, using both HemeChip and the clinical standard laboratory method, High Performance Liquid Chromatography (HPLC, VARIANT™ II, Bio-Rad Laboratories, Inc., Hercules, California). HemeChip tests were done on eHealth Africa campus in Kano, Nigeria, by trained local healthcare workers using blood samples collected at the nearby Aminu Kano Teaching Hospital. Clinical standard (HPLC) testing was done independently by the International Foundation Against Infectious Disease in Nigeria (IFAIN, Abuja, Nigeria) for the blood samples obtained in Kano or by the University Hospitals Cleveland Medical Center Clinical Laboratories (Cleveland, Ohio) for the blood samples obtained in Cleveland. Test results included the following: homozygous SCD (HbSS), heterozygous sickle hemoglobin C disease (HbSC), heterozygous sickle trait (HbAS), and normal (HbAA). HemeChip identified the subjects with HbSS with 100% accuracy, HbSC with 100% accuracy, HbAS with 98.2% accuracy, and HbAA with 96.4% accuracy in comparison to HPLC (Table 1). Overall accuracy of HemeChip was 97.2% in comparison to HPLC for the subjects tested. HemeChip sensitivity was 100% for all hemoglobin variants tested (Table 2), and specificity was 96.4% for HbSS vs. HbAA, 98.2% for HbSS vs. HbAS, 100% for HbSC vs. HbAS, and 100% for HbAS vs. HbAA. Bland-Altman analysis indicated strong agreement between the quantitative HPLC and HemeChip results for hemoglobin percentages, with a mean bias of -3.2%. HemeChip enables, for the first time, accurate, cost-effective identification and quantification of hemoglobin variants at the point-of-need. HemeChip has been developed based on a versatile, mass-producible microchip electrophoresis platform technology that may address other unmet needs in biology and medicine that require rapid, decentralized hemoglobin or protein analysis, identification, and/or quantification. Disclosures Thota: Hemex Health Inc: Employment. Little:PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; NHLBI: Research Funding; Doris Duke Charitable Foundations: Research Funding.

scholarly journals Aptamer-Based Diagnostic Systems for the Rapid Screening of TB at the Point-of-Care

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1352
Author(s):  
Darius Riziki Martin ◽  
Nicole Remaliah Sibuyi ◽  
Phumuzile Dube ◽  
Adewale Oluwaseun Fadaka ◽  
Ruben Cloete ◽  
...  
Keyword(s):  
Low Income ◽  
Point Of Care ◽  
Health Care Systems ◽  
Cost Effective ◽  
Rapid Screening ◽  
Low Income Countries ◽  
Sputum Smear ◽  
Diagnostic Systems ◽  
Molecular Tests ◽  
Rapid Tests

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.

scholarly journals Manufacture of Platelets from Human Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells: Functional Comparison to Concentrate Platelets

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1028-1028
Author(s):  
Keiichi Tozawa ◽  
Yukako Ono-Uruga ◽  
Masaki Yazawa ◽  
Taisuke Mori ◽  
Noriko Takizawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Application ◽  
Research Funding ◽  
Cellular Therapy ◽  
Recipient Mouse ◽  
Blood Samples ◽  
Equity Ownership ◽  
Induced Aggregation ◽  
Kinetics Of

Abstract We have established human adipose-derived mesenchymal stromal/stem cell line (ASCL) as an expandable cell source to generate megakaryocytes (MKs) releasing platelets for clinical transfusion. The use of ASCL has an advantage in manufacturing platelets, because both establishment of ASCL and its differentiation to MKs and platelets do not require gene transfer, and its endogenous thrombopoietin (TPO) is utilized for their differentiation. Here we report characterization of ASCL and ASCL-derived platelets for clinical application. ASCL retained their proliferation capacity for 6 months. There was no abnormality by karyotype analysis for ASCL, and no gene mutations registered in database for cancer and other diseases were noted by next-generation sequence analysis (n=3). ASCL satisfies the minimal criteria for defining mesenchymal stem cells by The International Society for Cellular Therapy: (1) adherence to plastic in vitro culture, (2) expression (>95% of cells) of CD73, CD90, and CD105 and no expression (<2% of cells) of CD45, CD34, CD14, CD19, and HLA-DR, and (3) capacity to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro. ASCL was cultured in 10 liters of MK lineage induction media using a bioreactor. The frequency of CD41-expressing MK-sized cells increased during this culture with a peak at Day 8 (60-70%). We detected increased gene expression of TPO, p45NF-E2, beta-1 tubulin, VWF, GATA2, PF4, FOG1, and Fli1 during this differentiation. ASCL-derived platelets were obtained with a peak at Day 12 with 30-50 platelets released from a single MK. The expression of intracellular factors, VWF, PF4, and beta-1 tubulin in these platelets (CD42b-positive/anuclear platelet-sized cells) was also observed by immunostaining. We next compared functionality of ASCL-derived platelets and concentrate platelets (CP) from the Japanese Red Cross Society. Upon stimulation with thrombin (0.5 U/mL), surface exposure of PAC-1 in ASCL-derived platelets was higher than that in CP (p<0.05). Similar to PAC-1 surface exposure, the binding of labeled fibrinogen or P-selectin to ASCL-derived platelets was higher than that to CP, though the differences were not statistically significant. A sufficient number of platelets were obtained to perform platelet aggregation study under light transmission aggregometry. Agonist (ADP 20 μM and calcium 10 mM)-induced aggregation was observed in both ASCL-derived platelets and CP. To investigate the kinetics of ASCL-derived platelets and CP, these cells (1 x 107 cells) were infused into irradiated immunodeficient NSG mice (2.0 Gy, 7 days). Blood samples from recipient mouse were analyzed for the presence of human platelets 0 mins, 30 mins, 2 hrs, and 24 hrs after infusion. The kinetics of ASCL-derived platelets was similar to those of CP at the peak with 2 hrs (n=3). We tested thrombus formation under flow condition. Blood samples labeled with anti-CD41 antibody (clone, SZ22) were perfused on a collagen-coated chip. Incorporation of cells expressing human CD41 into the thrombi was observed in both samples from ASCL-derived platelet- and CP-infused mouse. Taken together, manufacturing platelets from ASCL in a large-scale culture and CP showed the similar in vivo kinetics and function, further supporting the clinical application of our approach. Disclosures Ono-Uruga: AdipoSeeds Inc.: Equity Ownership. Okamoto:Nippon Shinyaku Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Toyama Chemical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Teijin Pharma Limited: Research Funding; Shionogi & Co., Ltd.: Research Funding; Bristol-Myers Squibb K.K.: Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Research Funding; Asahi Kasei Pharma Corp.: Research Funding; Pfizer Inc.: Honoraria, Research Funding; JCR Pharmaceuticals Co., Ltd.: Research Funding. Ikeda:AdipoSeeds Inc.: Equity Ownership. Matsubara:AdipoSeeds Inc.: Equity Ownership; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Tosoh Corporation: Research Funding; Nissui Pharmaceutical Co., Ltd.: Research Funding; Fujimori Kogyo Co., Ltd.: Research Funding.

scholarly journals A Longitudinal Study to Identify and Assess Adhesion Indices during Vaso-Occlusive Crises in Adults and Adolescents with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1097-1097
Author(s):  
Jennell White ◽  
Xiufeng Gao ◽  
Ke Liu ◽  
Michael U. Callaghan ◽  
Patrick C. Hines
Keyword(s):  
Steady State ◽  
Longitudinal Study ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Disease ◽  
Advisory Committees ◽  
Blood Samples ◽  
Equity Ownership ◽  
Adhesion Index ◽  
At Home

Abstract Sickle cell disease (SCD) is characterized by frequent and unpredictable vaso-occlusive complications (VOCs); however, there are no objective measures for VOC as a clinical endpoint. Vaso-occlusion results from processes that reduce blood flow in the microvasculature, including red cell stickiness and erythrocyte sickling. These processes lead to pain, chronic organ damage, and decreased life expectancy. The decision to seek medical contact varies amongst patients. When VOCs are managed at home valuable information remains unknown. We designed a longitudinal, observational study to capture adhesion data at home and in a hospital setting. The objective of this study was to determine whether a standardized, flow-based adhesion bioassay is capable of identifying VOCs occurring in SCD patients with varying degrees of medical contact. SCD patients (n=33) were evaluated over a 6-month period. Blood samples were collected every 3 weeks; when patients report a VOC corresponding blood samples are collected and steady state samples are resumed. During 6 months of evaluation, longitudinal measures of pain and clinical laboratory and biomarker samples from SCD patients (+/- hydroxyurea therapy) in steady state to VOC were studied. Blood samples were collected in sodium citrate from SCD subjects at steady state and during VOCs. Blood samples were perfused through VCAM-1-coated microchannels at standard physiologic flow conditions (1dyne/cm2, 1.67Hz). An adhesion index was established by quantifying adherent cells within a standard viewing area (cells/mm2), and could be obtained within 6-9 min. Adhesion indices varied from sample-to-sample at baseline (n=289; mean = 355 ± 235; median = 297 cells/mm2) and during VOC (n=59, mean=416±233, median=390). Repeated measures of adhesion over 6 months reveals significant intra-patient associations with C-reactive protein (CRP, n=335, r=0.16; p=0.006), lactose dehydrogenase (LDH, n=336, r=0.12; p=0.032), white blood cells (WBC, n=341, r=0.13; p=0.019), and reticulocyte percent (n=336, r=0.37, p<0.0001). The results also show significant inter-patient (n=35) correlations with CRP (r=0.34, p=0.047), fetal hemoglobin (HbF, r=-0.61, p=0.0001), reticulocyte percent (r=0.63, p<0.0001), reticulocyte (r=0.77, p<0.0001), and uric acid (r=0.37, p=0.028). At-home VOC adhesion indices (n=33; mean=482±255) were significantly higher than both ER-based VOC (n=8; mean=322± 153; p=0.031) and hospital-based VOC (n=18, mean=336±182; p=0.018) adhesion indices. The difference between at home VOC adhesion indices and baseline adhesion indices approached significance (482 ± 255 vs 355 ± 235, p=0.088). This study represents the largest longitudinal study of adhesion indices using a standardized clinical assay. These data confirm the normal range and longitudinal variability of SCD adhesion indices at baseline and during VOC. Adhesion increased during patient-reported VOCs in a subpopulation of individuals with SCD, suggesting there may be a subphenotype who are more predisposed to adhesion-mediated VOCs. At-home VOCs are likely higher because ER-VOC indices are influenced by fluid boluses, blood transfusions, or anti-inflammatory therapy. Further studies are underway to determine if a clinical adhesion index can effectively monitor response to SCD-modifying therapies and prospectively predict disease progression. Disclosures White: functional fluidics: Equity Ownership. Gao:Functional Fluidics: Equity Ownership. Liu:Functional Fluidics: Equity Ownership. Callaghan:Bioverativ: Honoraria; Alnylam Pharmaceuticals: Equity Ownership; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria; Sancilio Pharmaceuticals Company: Employment; Novo Nordisk: Employment, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Hema Pharmaceuticals: Honoraria; Grifols: Honoraria; Pfizer: Employment, Honoraria, Research Funding; Roche/Genentech: Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Employment; Global Blood Therepeutics: Employment. Hines:functional fluidics: Equity Ownership.

scholarly journals Assessment of Bleeding Phenotype in Hemophilia Α By a Novel Point-of-Care Global Assay

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4662-4662
Author(s):  
Debnath Maji ◽  
Michael A Suster ◽  
Divyaswathi Citla Sridhar ◽  
Maria Alejandra Pereda ◽  
Janet Martin ◽  
...  
Keyword(s):  
Whole Blood ◽  
Research Funding ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Point Of Care ◽  
Blood Samples ◽  
Healthy Group ◽  
Significant Difference ◽  
Bleeding Score ◽  
Bleeding History

Introduction: Patients with Hemophilia A have considerable phenotypic heterogeneity with respect to clinical severity based on their baseline factor levels. As clinical bleeding risk is helpful to individualize factor replacement therapy in hemophilia patients, previous studies have utilized direct and indirect methods of thrombin generation to classify individual bleeding phenotypes, however, with variable results. An easy to use, point-of-care, global assay to assess bleed phenotype, can be a useful tool in the clinical setting to determine intensity of prophylaxis therapy for patients with hemophilia. We have previously introduced a novel, point-of-care (POC), dielectric microsensor, ClotChip, and demonstrated its sensitivity to factor replacement in patients with severe hemophilia A. We aim to further test the ability of ClotChip in assessment of a bleeding phenotype, as described by a bleeding score, in patients with hemophilia A. Methods: After IRB approval, 28 patients with hemophilia A of varying severity and well-characterized bleeding history, were enrolled in this study at the time of trough factor levels. The bleeding history was extracted from patient charts and included number of bleeds (joint and soft-tissue), annual factor usage in terms of units/kg, and number of target joints. These parameters were used to generate a bleeding score (range: 0 - 24), and patients were divided in to 2 categories with scores between 0 - 12 (n=14) and > 12 (n=14). Healthy volunteers (n=17) were accrued as controls. Whole blood samples were obtained by venipuncture into collection tubes containing 3.2% sodium citrate. Samples were then tested with the ClotChip within 2 hours of collection. ClotChip is based on the electrical technique of dielectric spectroscopy (DS) and features a low-cost (material cost < $1), small- sized (26mm × 9mm × 3mm), and disposable microfluidic biochip with miniscule sample volume (< 10 µL). The ClotChip readout was taken as the temporal variation in the real part of blood dielectric permittivity at 1 MHz. Our previous studies have shown that the ClotChip readout is sensitive to the global coagulation process and the time to reach a peak in permittivity (Tpeak) is a sensitive parameter to assess coagulation factor defects. Thrombin generation assay (TGA) using low tissue factor concentration was also performed on blood samples according to the manufacturer's direction. TGA was not available for 4 hemophilia and 2 control samples. Endogenous thrombin potential (ETP) parameter of TGA was used in this study to assess thrombin generation. Data are reported as mean ± standard deviation (SD). Analysis of variance (ANOVA) was used to test for statistical significance between groups with P < 0.05. Spearman's correlation test was used to derive correlation statistics. Results: ClotChip exhibited a mean Tpeak of 2186s ± 1560s for hemophilia patients in the group with higher bleeding scores (i.e. score >12), a mean Tpeak of 931s ± 496s for the group with lower bleeding scores (i.e. score <12) and a mean Tpeak of 441s ± 74s for the healthy group (Figure 1A). A significant difference in Tpeak was found between the group with higher bleeding scores compared to the group with lower bleeding scores (P = 0.002) as well as between higher bleeding scores and the healthy group (P < 0.0001). However, no significant difference in the TGA ETP parameter was detected between the groups with higher bleeding scores (mean ETP: 470 ± 814) and lower bleeding scores (mean ETP: 471 ± 897) (Figure 1B). ETP exhibited a statistical difference between the healthy group (mean ETP: 3462 ± 575) and both hemophilia groups (P < 0.0001). We also carried out studies to investigate the correlative power of the ClotChip Tpeak parameter to the TGA ETP parameter when including additional blood samples that were collected at various times during a hemophilia patient's prophylaxis regimen. The ClotChip Tpeak parameter exhibited strong negative correlation to the TGA ETP parameter (Spearman's rs= -0.73, P < 0.0001). Conclusions: Our studies suggest that a novel dielectric microsensor (ClotChip) could be useful in assessing bleeding phenotype in hemophilia A patients, allowing rapid assessment of hemostasis using a miniscule amount of whole blood (<10 µL) at the POC. Further studies are needed to determine if ClotChip data can be used to individualize prophylactic factor replacement regimens in hemophilia A patients. Disclosures Maji: XaTek, Inc: Patents & Royalties: 9,995,701. Suster:XaTek, Inc: Consultancy, Patents & Royalties: 9,995,701. Mohseni:XaTek, Inc: Consultancy, Patents & Royalties. Ahuja:XaTexk Inc.: Consultancy, Patents & Royalties, Research Funding; Rainbow Children's Foundation: Research Funding; Bayer: Consultancy; Biovertiv Sanofi: Consultancy; Genentech: Consultancy.

scholarly journals Point of Care Diagnostics in Resource-Limited Settings: A Review of the Present and Future of PoC in Its Most Needed Environment

Biosensors ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 133
Author(s):  
Benjamin Heidt ◽  
Williane Siqueira ◽  
Kasper Eersels ◽  
Hanne Diliën ◽  
Bart van Grinsven ◽  
...  
Keyword(s):  
Low Income ◽  
Value Chain ◽  
Point Of Care ◽  
Healthcare Providers ◽  
Low Income Countries ◽  
Patient Treatment ◽  
Resource Limited Settings ◽  
Widespread Application ◽  
Resource Limited ◽  
Fundamental Research

Point of care (PoC) diagnostics are at the focus of government initiatives, NGOs and fundamental research alike. In high-income countries, the hope is to streamline the diagnostic procedure, minimize costs and make healthcare processes more efficient and faster, which, in some cases, can be more a matter of convenience than necessity. However, in resource-limited settings such as low-income countries, PoC-diagnostics might be the only viable route, when the next laboratory is hours away. Therefore, it is especially important to focus research into novel diagnostics for these countries in order to alleviate suffering due to infectious disease. In this review, the current research describing the use of PoC diagnostics in resource-limited settings and the potential bottlenecks along the value chain that prevent their widespread application is summarized. To this end, we will look at literature that investigates different parts of the value chain, such as fundamental research and market economics, as well as actual use at healthcare providers. We aim to create an integrated picture of potential PoC barriers, from the first start of research at universities to patient treatment in the field. Results from the literature will be discussed with the aim to bring all important steps and aspects together in order to illustrate how effectively PoC is being used in low-income countries. In addition, we discuss what is needed to improve the situation further, in order to use this technology to its fullest advantage and avoid “leaks in the pipeline”, when a promising device fails to take the next step of the valorization pathway and is abandoned.

scholarly journals Accuracy and Precision of a Point-of-Care HbA1c Test

2019 ◽  
Vol 14 (5) ◽  
pp. 883-889
Author(s):  
William D. Arnold ◽  
Kenneth Kupfer ◽  
Randie R. Little ◽  
Meera Amar ◽  
Barry Horowitz ◽  
...  
Keyword(s):  
Whole Blood ◽  
Point Of Care ◽  
Venous Blood ◽  
Reference Laboratory ◽  
Test Results ◽  
Blood Samples ◽  
Accuracy And Precision ◽  
The Mean ◽  
Whole Blood Samples ◽  
Highly Correlated

Background: Point-of-care (POC) hemoglobin A1c (HbA1c) testing has advantages over laboratory testing, but some questions have remained regarding the accuracy and precision of these methods. The accuracy and the precision of the POC Afinion™ HbA1c Dx test were investigated. Methods: Samples spanning the assay range were collected from prospectively enrolled subjects at three clinical sites. The accuracy of the POC test using fingerstick and venous whole blood samples was estimated via correlation and bias with respect to values obtained by an NGSP secondary reference laboratory (SRL). The precision of the POC test using fingerstick samples was estimated from duplicate results by calculating the coefficient of variation (CV) and standard deviation (SD), and separated into its components using analysis of variance (ANOVA). The precision of the POC test using venous blood was evaluated from samples run in four replicates on each of three test cartridge lots, twice per day for 10 consecutive days. The SD and CV by study site and overall were calculated. Results: Across the assay range, POC test results from fingerstick and venous whole blood samples were highly correlated with results from the NGSP SRL ( r = .99). The mean bias was −0.021% HbA1c (−0.346% relative) using fingerstick samples and −0.005% HbA1c (−0.093% relative) using venous samples. Imprecision ranged from 0.62% to 1.93% CV for fingerstick samples and 1.11% to 1.69% CV for venous samples. Conclusions: The results indicate that the POC test evaluated here is accurate and precise using both fingerstick and venous whole blood.

3D Printing of Microfluidics for Point of Care Diagnosis

2017 ◽  
Author(s):  
John P. Sibbitt ◽  
Mei He
Keyword(s):  
3D Printing ◽  
Low Income ◽  
Point Of Care ◽  
Low Cost ◽  
High Sensitivity ◽  
Disease Diagnosis ◽  
Low Income Countries ◽  
3D Design ◽  
Resource Limited ◽  
Production Techniques

Microfluidic lab-on-a-chip (MLOC) technology is a promising approach for point-of-care (POC) diagnosis; low reagent consumption, high sensitivity and quick analysis time are the most prominent benefits. However, microfabrication of MLOCs utilizes specialized techniques and infrastructure, making conventional fabrication time consuming and difficult. While relatively inexpensive production techniques exist for POC diagnoses, such as replication of polymer-based (e.g., PDMS) microfluidic POC devices on lithographic molds, this approach has limitations including: further hydrophilic surface modifications of PDMS, inability to change lithographic mold Z dimensions, and slow prototyping. In contrast, stereo-lithographical (SLA) printing can integrate all of the necessary fabrication resources in one instrument, allowing highly versatile microfluidic devices to be made at low cost. In this paper, we report two microfabrication approaches of microfluidics utilizing (SLA) 3D printing technology: I) Direct SLA printing of channels and structures of a monolithic microfluidic POC device; II) Indirect fabrication, utilizing SLA 3D printed molds for PDMS based microfluidic device replication. Additionally, we discuss previous work providing a proof of concept of applications in POC diagnosis, using direct 3D printing fabrication (approach I). The robustness and simplicity of these protocols allow integrating 3D design and microfabrication with smartphone-based disease diagnosis as a stand-alone system, offering strong adaptability for establishing diagnostic capacity in resource-limited areas and low-income countries.

scholarly journals Field Evaluation of Xpert HPV Point-of-Care Test for Detection of Human Papillomavirus Infection by Use of Self-Collected Vaginal and Clinician-Collected Cervical Specimens

2016 ◽  
Vol 54 (7) ◽  
pp. 1734-1737 ◽  
Author(s):  
P. Toliman ◽  
S. G. Badman ◽  
J. Gabuzzi ◽  
S. Silim ◽  
L. Forereme ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Low Income ◽  
Point Of Care ◽  
Cervical Screening ◽  
Field Evaluation ◽  
World Health ◽  
Low Income Countries ◽  
High Burden ◽  
Screening Programs ◽  
Hpv Test

The World Health Organization has recommended that testing for high-risk human papillomavirus (HPV) (hrHPV) infection be incorporated into cervical screening programs in all settings worldwide. In many high-burden, low-income countries, it will not be feasible to achieve high cervical screening coverage using hrHPV assays that require clinician-collected samples. We conducted the first evaluation of self-collected vaginal specimens compared with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. Women aged 30 to 54 years attending two well-woman clinics in Papua New Guinea were invited to participate and provided self-collected vaginal and clinician-collected cervical cytobrush specimens. Both specimen types were tested at the point of care by using the Xpert HPV test. Women were given their cervical test result the same day. Those with a positive hrHPV test and positive examination upon visual inspection of the cervix with acetic acid were offered same-day cervical cryotherapy. A total of 1,005 women were enrolled, with 124 (12.3%; 95% confidence interval [CI], 10.3%, 14.4%) being positive for any hrHPV infection. There was a 99.4% overall percent agreement (OPA) between vaginal and cervical tests for HPV-16 (95% CI, 98.9%, 99.9%), a 98.5% OPA for HPV-18/45 (95% CI, 97.7%, 99.3%), a 94.4% OPA for other hrHPV infections (95% CI, 92.9%, 95.9%), and a 93.4% OPA for all hrHPV types combined (95% CI, 91.8%, 95.0%). Self-collected vaginal specimens had excellent agreement with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. This approach provides for the first time an opportunity to incorporate point-of-care hrHPV testing into clinical cervical screening algorithms in high-burden, low-income settings.

Diagnostic accuracy of three clinical dehydration scales: a systematic review

2017 ◽  
Vol 103 (4) ◽  
pp. 383-388 ◽  
Author(s):  
Anna Falszewska ◽  
Hania Szajewska ◽  
Piotr Dziechciarz
Keyword(s):  
Diagnostic Accuracy ◽  
Low Income ◽  
Positive Likelihood Ratio ◽  
High Income ◽  
Low Income Countries ◽  
Severe Dehydration ◽  
Post Test ◽  
Sensitivity Specificity ◽  
Post Test Probability ◽  
Test Probability

ObjectiveTo systematically assess the diagnostic accuracy of the Clinical Dehydration Scale (CDS), the WHO Scale and the Gorelick Scale in identifying dehydration in children with acute gastroenteritis (AGE).DesignThree databases, two registers of clinical trials and the reference lists from identified articles were searched for diagnostic accuracy studies in children with AGE. The index tests were the CDS, WHO Scale and Gorelick Scale, and reference standard was the percentage loss of body weight. The main analysed outcomes were the sensitivity, specificity, positive likelihood ratio (LR) and negative LR.ResultsTen studies were included. In high-income countries, the CDS provided a moderate-to-large increase in the post-test probability of predicting moderate to severe (≥6%) dehydration (positive LR 3.9–11.79), but it was of limited value for ruling it out (negative LR 0.55–0.71). In low-income countries, the CDS showed limited value both for ruling in and ruling out moderate-to-severe dehydration. In both settings, the CDS showed poor diagnostic accuracy for ruling in or out no dehydration (<3%) or some dehydration (3%–6%). The WHO Scale showed no or limited value in assessing dehydration in children with diarrhoea. With one exception, the included studies did not confirm the diagnostic accuracy of the Gorelick Scale.ConclusionLimited evidence suggests that the CDS can help in ruling in moderate-to-severe dehydration (≥6%) in high-income settings only. The WHO and Gorelick Scales are not helpful for assessing dehydration in children with AGE.

Sign in / Sign up

Export Citation Format

Share Document