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A Novel Real-Time PCR Assay for Detection of HLA-A*31:01 in Individuals Being Considered for Carbamazepine Therapy
- David S. Krause, Kathleen Davis, Daniel Dowd, David J. Robbins
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, pp. 154-155
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Background
Carbamazepine, an anticonvulsant also used as a mood stabilizer and for trigeminal neuralgia, is associated with serious, sometimes fatal cutaneous adverse drug reactions, including Stevens Johnson Syndrome and toxic epidermal necrolysis1. Current literature demonstrates a genetic predisposition linked to specific class I and II human leukocyte antigen (HLA) types in various ethnic populations2. HLA-A*31:01 is one such HLA type, and is routinely identified by the tag SNP rs1061235. However, rs1061235 has poor specificity for HLA*31:01 due to interference of HLA-A*33 types3. We investigated the false positive rate in our population and developed a novel real-time PCR assay that distinguishes HLA-A*31:01 from other HLA-A types including HLA-A*33.
Methods120 unique samples were tested in triplicate during the validation of this assay and were sent to a reference lab for HLA next generation sequencing (NGS) typing, including 89 in-house samples and 31 Coriell samples with documented HLA typing results. The results from our real-time PCR assay were compared to the HLA typing results. HLA typing results were also compared to the tag SNP rs1061235 results to calculate the false positive rate.
ResultsThere was 100% concordance between our real-time PCR results and expected results based on HLA typing. 89 sample results for tag SNP rs1061235 were compared to HLA typing results. 75/89 samples had a rs1061235 variant, but 31/75 (41%) samples did not have the HLA-A*31:01 type, thus defining the false positive rate of the tag SNP for our population. We theorized there would be a small subset of rare HLA-A types that would interfere with the assay and we tested the three types available to us. We confirmed that 3 of the HLA types (HLA-A*31:04, 31:12, and 31:16) result falsely positive due to sequence homology with 31:01. There is no known literature indicating whether these rare HLA-A*31 subtypes are associated with cutaneous adverse reactions. These 3 HLA types and the other suspected interfering HLA types have limited frequency data sets and are expected to occur rarely in our patient population; we expect these HLA types make up less than 0.003% of the our population. Our assay specificity for the validation is >99%.
ConclusionsOur custom real-time PCR assay for detection of HLA-A*31:01 is significantly more specific than the commonly used tag SNP rs1061235. Clinicians considering carbamazepine therapy for their patients will have a better understanding of cutaneous adverse reaction risk and can make improved personalized treatment decisions. This quick, cost effective assay allows more patients in need of carbamazepine treatment to benefit from its use.
FundingGenomind, Inc.
Pilot Study of Postexposure Prophylaxis for Hepatitis C Virus in Healthcare Workers
- Kathleen E. Corey, Julie C. Servoss, Deborah R. Casson, Arthur Y. Kim, Gregory K. Robbins, Jean Franzini, Katherine Twitchell, Susan C. Loomis, Diane R. Abraczinskas, Adam M. Terella, Jules L. Dienstag, Raymond T. Chung
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 30 / Issue 10 / October 2009
- Published online by Cambridge University Press:
- 02 January 2015, pp. 1000-1005
- Print publication:
- October 2009
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Background and Objective.
Hepatitis C virus (HCV) transmission occurs in 0.2%-10% of people after accidental needlestick exposures. However, postexposure prophylaxis is not currently recommended. We sought to determine the safety, tolerability, and acceptance of postexposure prophylaxis with peginterferon alfa-2b in healthcare workers (HCWs) exposed to blood from HCV-infected patients.
Design.Open-label pilot trial of peginterferon alfa-2b for HCV postexposure prophylaxis.
Setting.TWO academic tertiary-referral centers.
Methods.HCWs exposed to blood from HCV-infected patients were informed of the availability of postexposure prophylaxis. Persons who elected postexposure prophylaxis were given weekly doses of peginterferon alfa-2b for 4 weeks.
Results.Among 2,702 HCWs identified with potential exposures to bloodborne pathogens, 213 (7.9%) were exposed to an HCV antibody-positive source. Of 51 HCWs who enrolled in the study, 44 (86%) elected to undergo postexposure prophylaxis (treated group). Seven subjects elected not to undergo postexposure prophylaxis (untreated group). No cases of HCV transmission were observed in either the treated or untreated group, and no cases occurred in the remaining 162 HCWs who did not enroll in this study. No serious adverse events related to a peginterferon alfa-2b regimen were recorded, but minor adverse events were frequent.
Conclusion.In this pilot study, there was a lower than expected frequency of HCV transmission after accidental occupational exposure. Although peginterferon alfa-2b was safe, because of the lack of HCV transmission in either the treated or untreated groups there is little evidence to support routine postexposure prophylaxis against HCV in HCWs.
6 - United States: popular, pragmatic and problematic
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- By Kathleen A. Robbins, General Manager of Cellular, One of East Central Illinois USA, Martha A. Turner, PhD Student Rutgers University in the School of Communication, Information and Library Studies
- Edited by James E. Katz, Rutgers University, New Jersey, Mark Aakhus, Rutgers University, New Jersey
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- Book:
- Perpetual Contact
- Published online:
- 22 September 2009
- Print publication:
- 21 March 2002, pp 80-93
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Summary
Introduction
Despite the enormous popularity and economic success of mobile phone communication in the United States, only slight scholarly attention has been paid to its social aspects (notable exceptions have been the studies of Katz and Aspden, 1998, and Katz, 1999). Researchers can ill-afford to ignore a technology not only that has been so widely adopted around the world, but whose success seems to have soared beyond even the most enthusiastic projections of those American companies that created the technology in the first place. AT&T, which first developed cellular technology in the early 1980s, estimated that the US market would in year 2000 be 1 million users. This figure was revised in mid-1994 to 120 million mobile phone users worldwide by 1999 (Common Carrier Week, June 6, 1994). In fact the figure was 97 million in June 2000 in the United States alone, and in mid-2001 there were 118 million US subscribers, according to the Cellular Telephone Industry Association (CTIA, 2000, 2001). Penetration is expected to grow to 176 million or 60% in 2004 and 232 million or 76% in 2009 (Paul Kagan Associates, 1999). Although these are impressive numbers, they pale in comparison with Finland's robust 69% penetration rate (Quinn, 1999).
Allied Business Intelligence (1999) estimated that Wireless Application Protocol (WAP) equipped mobile phones would be 12% of the market in 2000 and 33% by 2005. WAP is one of protocols that are being developed to allow mobile phone access to the Internet.
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