Validating an ontology-based algorithm to identify patients with Type 2 Diabetes Mellitus in Electronic Health Records

BackgroundImproving healthcare for people with chronic conditions requires clinical information systems that support integrated care and information exchange, emphasizing a semantic approach to support multiple and disparate Electronic Health Records (EHRs). Using a literature review, the Australian National Guidelines for Type 2 Diabetes Mellitus (T2DM), SNOMED-CT-AU and input from health professionals, we developed a Diabetes Mellitus Ontology (DMO) to diagnose and manage patients with diabetes. This paper describes the manual validation of the DMO-based approach using real world EHR data from a general practice (n = 908 active patients) participating in the electronic Practice Based Research Network (ePBRN).MethodThe DMO-based algorithm to query, using Semantic Protocol and RDF Query Language (SPARQL), the structured fields in the ePBRN data repository were iteratively tested and refined. The accuracy of the final DMO-based algorithm was validated with a manual audit of the general practice EHR. Contingency tables were prepared and Sensitivity and Specificity (accuracy) of the algorithm to diagnose T2DM measured, using the T2DM cases found by manual EHR audit as the gold standard. Accuracy was determined with three attributes – reason for visit (RFV), medication (Rx) and pathology (path) – singly and in combination.ResultsThe Sensitivity and Specificity of the algorithm were 100% and 99.88% with RFV; 96.55% and 98.97% with Rx; and 15.6% and 98.92% with Path. This suggests that Rx and Path data were not as complete or correct as the RFV for this general practice, which kept its RFV information complete and current for diabetes. However, the completeness is good enough for this purpose as confirmed by the very small relative deterioration of the accuracy (Sensitivity and Specificity of 97.67% and 99.18%) when calculated for the combination of RFV, Rx and Path. The manual EHR audit suggested that the accuracy of the algorithm was influenced by data quality such as incorrect data due to mistaken units of measurement and unavailable data due to non-documentation or documented in the wrong place or progress notes, problems with data extraction, encryption and data management errors.ConclusionThis DMO-based algorithm is sufficiently accurate to support a semantic approach, using the RFV, Rx and Path to define patients with T2DM from EHR data. However, the accuracy can be compromised by incomplete or incorrect data. The extent of compromise requires further study, using ontology-based and other approaches.     

Quantification of tryptase-TIM-3 double-positive mast cells in human chronic periodontitis

ObjectivesMast cells (MCs) are implicated in the pathogenesis of allergic reactions and inflammatory conditions through the release of inflammatory mediators. So far limited attention has been given to the role of MCs in periodontitis. T cell immunoglobulin mucin domain (TIM)-3 is an immunomodulatory molecule and influences MC function. However, whether TIM-3 is expressed on MCs in the process of human periodontal disease has not been reported. Therefore, we identified MCs by toluidine blue staining and examined the expression of TIM-3 on tryptase-positive MCs in different severities of human chronic periodontitis using double-immunofluorescence staining in this study.Material and methodsA total of 83 human periodontal specimens were involved in this study, including healthy control tissues (n = 25), chronic moderate periodontitis (n = 28), and chronic severe periodontitis (n = 30). The gingival specimens were fixed in 10% buffered formalin, stained with haematoxylin and eosin for histopathology, with toluidine blue for MCs, and with double-immunofluorescence for identification of tryptase-TIM-3 double-positive MCs in gingival tissues.ResultsCompared with healthy controls, the score of gingival tissue inflammation was significantly increased in the chronic moderate periodontitis (P = 0.013) and chronic severe periodontitis (P < 0.0001), and the densities (cells/mm²) of tryptase-TIM-3 double-positive MCs were significantly increased in both the chronic moderate (P = 0.011) and severe periodontitis groups (P < 0.0001). However, compared with the chronic moderate periodontitis group, both the score of gingival tissue inflammation (P = 0.012) and the density of tryptase-TIM-3 double-positive MCs (P = 0.011) in gingival tissue were significantly increased in the severe periodontitis groups.ConclusionSignificantly increased number of tryptase-TIM-3 double-positive MCs had the similar tendency as the severity of periodontitis inflammation in human chronic periodontitis. Our data suggest that TIM-3 may have a role on MCs in human chronic periodontitis.     

A review of the prevalence of Autism Spectrum Disorder in Asia

Electronic databases and bibliographies were searched for English language articles on the prevalence of Autism Spectrum Disorder in Asia over time to estimate prevalence. The overall reported prevalence of ASD in recent studies was higher than the previously reported in Asia. The average prevalence of ASD before 1980 was around 1.9/10,000 while it was 14.8/10,000 from 1980 to present. The median prevalence of ASD among 2–6-year-old children who are reported in China from 2000 upwards was 10.3/10,000. ASD is probably more common in Asia than previously thought.     

Antenatal Rh prophylaxis is unnecessary for “Asia type” DEL women

BackgroundGenerally Rh-negative patients need to be transfused with Rh-negative red blood cells. For pregnant women carrying Rh-positive fetus, the antenatal anti-D detection and Rh immunoglobulin prophylaxis are required worldwide. In East Asia, a RhD variant, termed “Asia type” DEL, was found in approximately 30% of apparent Rh-negative individuals. The antigenic and molecular properties of the DEL were previously defined. Few data discuss whether DEL could be immunized by D antigen clinically although DEL was reported arousing alloimmunization to true Rh-negative patients.Study design and methodsTo determine whether the DEL variant can be immunized to the D antigen, we retrospectively evaluated 104 Rh-negative pregnancies with allo-anti-D antibodies, and we also tracked 199 consecutive apparent Rh-negative pregnant women, with a history of gestations or parturitions but not subject to anti-D gamma-globulin prophylaxis, for evidence of allo-anti-D. The DEL variant was first excluded by ccee phenotypes and then identified through PCR analysis or sequencing.ResultsIn the retrospective study, we expected to find 30 DEL variants, yet none of the anti-D alloimmunized women were DEL-positive. And in the second group, none of 44 DEL-positive women versus 38 of 155 (24.5%) true Rh-negative women (those excluding DEL) formed allo-anti-D.ConclusionThe data indicate that the “Asia type” DEL variant does not appear at risk of alloimmunization to the D antigen. It strongly suggests that the antenatal Rh immune globulin prophylaxis is unnecessary for DEL women. Furthermore, it implicates that the “Asia type” DEL may be deemed Rh-positive safely for clinical transfusion therapy.     

A scintillation proximity assay for dengue virus NS5 2′-O-methyltransferase—kinetic and inhibition analyses

Dengue virus (DENV) NS5 possesses methyltransferase (MTase) activity at its N-terminal amino acid sequence and is responsible for formation of a type 1 cap structure, m⁷GpppAm^2′-O in the viral genomic RNA. Optimal in vitro conditions for DENV2 2′-O-MTase activity were characterized using purified recombinant protein and a short biotinylated GTP-capped RNA template. Steady-state kinetics parameters derived from initial velocities were used to establish a robust scintillation proximity assay for compound testing. Pre-incubation studies showed that MTase–AdoMet and MTase–RNA complexes were equally catalytically competent and the enzyme supports a random bi bi kinetic mechanism. The assay was validated with competitive inhibitory agents, S-adenosyl-homocysteine and two homologues, sinefungin and dehydrosinefungin. A GTP-binding pocket present at the N-terminal of DENV2 MTase was previously postulated to be the cap-binding site. Interestingly, inhibition of the enzyme by GTP was two-fold lower than with RNA cap analogues, G[5′]ppp[5′]A and m⁷G[5′]ppp[5′]A and about three-fold poorer than a two-way methylated analogue, m⁷G[5′]ppp[5′]m⁷G. This assay allows rapid and highly sensitive detection of 2′-O-MTase activity and can be readily adapted for high-throughput screening for inhibitory compounds. It is suitable for determination of enzymatic activities of a wide variety of RNA capping MTases.     

用逆转录—聚合酶链反应检测海南岛登革热流行区？…

目的 寻找中国海南岛一带登革热疫区，登革病毒潜伏的动物宿主及鉴定其毒株型别。方法 采用１￣４型登革病毒通用引物，用塑转录－聚合酶链反应（ＲＴ－ＰＣＲ）检测海南岛登革热流行区蝙蝠脑细胞，血清和埃及伊蚊的登革病毒ＲＮＡ。结果 检测３５例疫区蝙蝠脑细胞，２０例阳性；检测１８例蝙蝠血清，３例阳性；检测三组埃及伊蚊，１组阳性，３组非流行区者都阴性。用４个登革病毒原型株的单克隆荧光抗体技术检测２０例登革病毒Ｒ