Effect of precision antiplatelet therapy based on CYP2C19/11-dhTxB2 variability in prognosis of ischemic stroke/TIA patients: study protocol for a multicenter randomized controlled trial

Background: Clopidogrel and aspirin are conventional drugs for treating ischemic stroke (IS) and transient ischemic attack (TIA). However, with the increase of clinical application, many patients have shown clopidogrel resistance (CR) and/or aspirin resistance (AR). clopidogrel resistance is related with cytochrome P450-2C19 (CYP2C19) polymorphism, and aspirin resistance is related to urine concentration of 11-dehydroxetane B2. At present, the effect of precision antiplatelet medication based on the cytochrome CYP2C19 genotype test and the 11-dhTxB2 test has not been evaluated prospectively in a large sample. Methods: This is a randomized controlled trial evaluating the effects of precision antiplatelet medication based on the CYP2C19 genotype test and the 11-dhTxB2 test on IS/TIA patients over 12 months. Outcomes of interest including stroke recurrence, neurologic disabilities defined by the Modified Rankin Scale (mRS), bleeding events, other adverse events, and all-cause mortality will be assessed at the 1st, 3rd, 6th and 12th-month post-discharge. Demographics, risk factors, laboratory investigations, medications, physiological tests, and brain imaging will also be assessed.Discussion: Some stroke patients have resistance to clopidogrel or aspirin, but there is still no personalized medicine. Our study will conduct free antiplatelet resistance tests and individualized antiplatelet medication for patients in the intervention group, ultimately evaluating individualized medication effectiveness through a one-year follow-up. The research results will help to assess the impact of personalized antiplatelet drug therapy on the prognosis of stroke, thus providing a reference for precise clinical treatment.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900026492. Registered on 12 October 2019.

1215. Evaluation of the Carba-R NxG Assay in a Global Challenge Set of Pseudomonas aeruginosa

Background Carbapenem-resistant P. aeruginosa (CRPA) is a growing clinical challenge. Carbapenemase production is particularly problematic due to high transmissibility and limited treatment options. Carbapenemase prevalence and diversity are largely driven by geography and thus testing spectrum will dictate utility in certain regions. The purpose of this study was to evaluate the performance of the research-use-only Xpert® Carba-R NxG (Carba-R NxG) and commercially available Xpert® Carba-R (Carba-R) in a global collection of P. aeruginosa. Methods The challenge set included 123 clinical P. aeruginosa isolates from 11 countries. Isolates were previously categorized via PCR or whole-genome sequencing. Carbapenemase classes tested include: VIM, IMP, NDM, SPM, KPC, and GES. Non-carbapenemase (non-CP) harboring isolates were also tested (negative control). Isolates were tested using the Carba-R NxG and the Carba-R per manufacturer instructions. Carba-R NxG testing was completed by Cepheid (Sunnyvale, CA) blinded to genotype. Test performances were tabulated for each assay by carbapenemase class. Results Both assays gave negative results for all non-CP isolates and positive results for all VIM, NDM, and KPC isolates. An improvement in IMP detection among isolates was observed (Carba-R NxG 100% vs. Carba-R 58% detection). All SPM and GES isolates, targets not present in the current Carba-R, were positive by Carba-R NxG. Two isolates harbored both VIM and GES, while a third isolate contained VIM and NDM. The Carba-R NxG identified both targets in all 3 isolates while the Carba-R was negative for both GES-containing isolates. Table 1 provides the test performance of both assays. Overall, the Carba-R NxG successfully categorized 100% of isolates tested compared with 68% for its predecessor. Table 1. Test performance of Carba-R NxG and Commercially Available Carba-R by Carbapenemase Class. Conclusion As the prevalence and diversity of carbapenemase-producing CRPA continues to expand, the Carba-R offers a rapid and sensitive assay to identify clinically relevant carbapenemase genotypes to inform infection prevention and therapeutic interventions. The Carba-R NxG will expand the current targets including SPM, GES, NMC/IMI, and IMP-subtypes, outside the previous testing spectrum, increasing the global utility of the test. Disclosures Isabella A. Tickler, BS, Cepheid (Employee) Caitlin dela Cruz, BS, Cepheid (Employee) Fred C. Tenover, PhD, Cepheid (Employee) David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)

Effect of precision antiplatelet therapy based on CYP2C19/11-dhTxB2 variability in prognosis of ischemic stroke/TIA patients: study protocol for a multicenter randomized controlled trial

Background: Clopidogrel and aspirin are conventional drugs for treating ischemic stroke (IS) and transient ischemic attack (TIA). However, with the increase of clinical application, many patients have shown clopidogrel resistance and/or aspirin resistance . clopidogrel resistance is related with cytochrome P450-2C19 (CYP2C19) poly m orphism , and aspirin resistance is related to urine concentration of 11-dehydroxetane B2. At present, the effect of precision antiplatelet medication based on the cytochrome CYP2C19 genotype test and the 11-dhTxB2 test has not been evaluated prospectively in a large sample. Methods: This is a randomized controlled trial evaluating the effects of precision antiplatelet medication based on the CYP2C19 genotype test and the 11-dhTxB2 test on IS/TIA patients over 12 months. Outcomes of interest including stroke recurrence, neurologic disabilities defined by the Modified Rankin Scale (mRS), bleeding events, other adverse events, and all-cause mortality will be assessed at the 1st, 3rd, 6th and 12th-month post-discharge. Demographics, risk factors, laboratory investigations, medications, physiological tests, and brain imaging will also be assessed. Discussion: Some stroke patients have resistance to clopidogrel or aspirin, but there is still no personalized medicine. Our study will conduct free antiplatelet resistance tests and individualized antiplatelet medication for patients in the intervention group, ultimately evaluating individualized medication effectiveness through a one-year follow-up. The research results will help to assess the impact of personalized antiplatelet drug therapy on the prognosis of stroke, thus providing a reference for precise clinical treatment. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900026492. Registered on 12 October 2019.

Incidence of Sickle Cell Anaemia among Children Attending Maryam Abacha Women and Children Hospital, Sokoto

Sickle Cell Anaemia is still considered the most common genetic disease worldwide, causing morbidity and mortality in Sub-Saharan Africa, Mediterranean areas, Middle East and India. Nigeria, being the most populous black nation in the world, bears its greatest burden in Sub-Saharan Africa. This study was conducted to determine the incidence of Sickle Cell Anaemia among children attending Maryam Abacha Women and Children Hospital, Sokoto. A total of one hundred (100) blood samples were examined for the disease. Out of the 100 children tested for the disease. (59%) were normal (HbAA), (35%) were carrier (HbAS) and (6%) were Sicklers (HbSS). The result based on gender showed that female has the highest percentage of the disease (5%) against male subjects with only (1%). A child between the age group 6-10 years has the highest rate of sickle cell anaemia (3%) while age group 11-15 years had the lowest rate of the infection. Improved knowledge regarding Sickle cell anaemia disease and its comprehensive care among Nigerian physicians will enhance quality of care for affected childrens and policy for regular genotype test by government and other stakeholders before marriage among Nigerians will help to prevent the disease.

A191 EFFICIENCY OF TAILORED ERADICATION REGIMEN BASED ON ANTIBIOTIC SUSCEPTIBILITY AND CYP2C19 GENOTYPE TESTING IN CHILDREN WITH REFRACTORY HELICOBACTER PYLORI INFECTION

Background Refractory helicobacter pylori (Hp) is a challenging problem for pediatric population. Whether Hp culture and CYP2C19 genotype need to be done together still remains contraversial. Aims To explore the efficiency of tailored eradication therapy based on helicobacter pylori culture, susceptibility and CYP2C19 genotype in children who failed to empirical Hp eradication strategy in Baoding region(China). Methods This study is an observational cohort study. A total of 156 children with Hp infection who failed to amoxicillin + clarithromycin +omeprazole triple regimen in Baoding Children’s Hospital were selected as study subjects, and 92 of them underwent Hp culture and CYP2C19 genetic testing. 75 cases with successful Hp culture were defined as successful culture group and were treated according to antibiotics sensitivity and genotype results. 17 cases with failed culture were defined as culture failure group and were treated only based on the results of CYP2C19 genotype. 64 children who did not agree to perform Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple therapy (amoxicillin + metronidazole + omeprazole + bismuth). Antibiotics resistance, CYP2C19 gene polymorphism and therapeutic efficiency between the three groups were compared and analyzed. Results Results of Hp culture and antibiotics susceptibility: among the 75 children with successful culture, 72 (96%) were resistant to clarithromycin, 3 (4%) were resistant to metronidazole, 5 (7%) were resistant to levofloxacin, 5 (7%) were resistant to rifampicin, 1 (1%) was resistant to tetracycline, and there was no resistance to amoxicillin and furazolidone. Results of CYP2C19 genotype test: among the 92 patients who underwent genotype test, 43 were Extensive Metabolizer (EM) (47%), 9 were Poor Metabolizer (PM) (10%), and 40 were Intermediate Metabolizer (IM) (44%). Efficiency results: eradication rate in the successful culture group, culture failure group and empirical eradication therapy group was 99% (74/75),88%(15/17) and 72%(46/64), respectively. The eradication rate of children in the culture failure group and the empirical eradication therapy group were both lower than that in the successful culture group,and there were no difference between empirical eradication therapy group and culture failure group(p=0.283). Conclusions Tailored treatment based on Hp culture + antibiotics susceptibility and CYP2C19 genotype detection should be performed in children with refractory Hp infection. Hp culture + antibiotics susceptibility plays a more important role than CYP2C19 genotype. Funding Agencies None

Association between Non-secretion of ABH Antigens and Sickle Cell Anaemia

Aim: To determine whether non-secretion of ABH blood group antigens was associated with Sickle Cell Anaemia. Materials and Methods: Haemaglutination inhibition test was carried out on saliva samples from 300 individuals; 100 of whom had haemoglobin (Hb) genotype AA, 100 HbAS, 50 HbAC and 50 HbSS. ABO blood grouping was carried out by standard methods and Haemoglobin genotype test was performed by cellulose acetate electrophoresis technique. Results: Eighteen percent (18%) of HbAA, 23% of HbAS, 18% of HbAC and 42% of HbSS individuals were non-secretors of ABH antigens (p = 0.007). Non-secretion of ABH substances was more associated with HbSS persons than HbAA (p = 0.002), HbAS (p = 0.016) and HbAC (p = 0.009) individuals. Conclusion: Non-secretion of ABH blood group substances is associated with Sickle Cell Anaemia.

Prevalence, survival outcomes, and clinicopathologic factors associated with negative high risk human papillomavirus in surgical specimens of cervical cancer with pretreatment negative DNA genotype test

ObjectiveThe aim of this study was to detect high risk human papillomavirus in cervical cancer with a pretreatment negative high risk human papillomavirus DNA genotype test and to evaluate clinicopathologic characteristics and survival outcomes according to high risk human papillomavirus status.MethodsWe investigated high risk human papillomavirus status in surgical specimens from 30 cases of cervical cancer using polymerase chain reaction. Polymerase chain reaction primers were set to detect the presence of the common L1 and E7 regions of human papillomavirus types 16, 18, 31, 33, 45, 52, and 58. We analyzed the following clinicopathologic parameters to evaluate their relationships with high risk human papillomavirus status: age, histology, stage, tumor size, invasion depth, lymphovascular invasion, and recurrent status.ResultsAmong 30 cases with a pretreatment negative DNA genotype test, high risk human papillomavirus was detected in 12 (40.0%), whereas 18 (60.0%) were negatives. Of 12 high risk human papillomavirus positive cases, 10 (33.3%) were positive for the L1 region, 6 (20.0%) of the 7 types were positive for the E7 region, and 4 (13.1%) were positive for both L1 and E7 regions. According to a multiple logistic regression model, tumor size (odds ratio 7.80; 95% confidence interval 1.476 to 41.216; P=0.0097) and stage (odds ratio 7.00; 95% confidence interval 1.293 to 37.910; P=0.0173) were associated with negative high risk human papillomavirus DNA status. Kaplan–Meier survival plots showed that negative high risk human papillomavirus status was associated with worse disease free survival in contrast with positive high risk human papillomavirus status (P=0.0392).ConclusionsNegative high risk human papillomavirus was found in 60% of cervical cancers with a pretreatment negative DNA genotype test. Moreover, the negative high risk human papillomavirus group was associated with worse survival outcome.

The Massachusetts Hepatitis C Testing Cascade, 2014-2016

Objectives: To characterize hepatitis C testing in Massachusetts and guide stakeholders in addressing the needs of people living with hepatitis C. Methods: All persons with a positive laboratory report for anti-hepatitis C virus (HCV) antibody, between 2014 and 2016, were included in the testing cascade. Outcomes were HCV tests received after a positive anti-HCV antibody test: nucleic acid test or genotype test. Logistic regression analyses were performed to determine factors associated with progression through the HCV testing cascade. Results: Among those reported anti-HCV antibody positive, a total of 13 194 (61%) cases had a subsequent RNA-based test, and 79% (10 374/13 194) were confirmed with current, active HCV infection. For confirmed HCV cases, 44% (4557/10 374) had a genotype identified. The median time from an antibody-positive test to a RNA-based test was 29 days (interquartile range [IQR] = 7-151). Differences in moving through the testing cascade were observed by birth cohort and race/ethnicity. Conclusions: Improved surveillance capture of demographic information is needed to help public health agencies ensure equity in HCV diagnosis and linkage to care.