State laws and policies to reduce opioid-related harm: A qualitative assessment of PDMPs and naloxone programs in ten U.S. States.

As the magnitude of the opioid epidemic grew in recent years, individual states across the United States of America enacted myriad policies to address its complications. We conducted a qualitative examination of the structure, successes, and challenges of enacted state laws and policies aimed at the opioid epidemic, with an in-depth focus on prescription drug monitoring programs (PDMPs) and naloxone access efforts. A set of 10 states (Florida, Kentucky, Massachusetts, Michigan, Missouri, New York, North Carolina, Tennessee, Washington, and West Virginia) was chosen a priori to achieve a varied sample of state policies and timing, as well as population opioid complications. Archival research was conducted to identify state-level policies aimed at the opioid epidemic and semi-structured interviews were conducted with 31 key stakeholders between March and September 2016. The most frequently mentioned key to success was an identifiable champion instrumental in leading the passage of these policies. The lack of a unified legislature and physician pushback were challenges many states faced in implementing policies. Champion-led task forces, stakeholders' personal stories garnering buy-in, ongoing education and feedback to PDMP users, and inclusive stakeholder engagement are critical aspects of passing and implementing state policies aimed at combating the opioid epidemic. Engaging all interested stakeholders and providing continuing feedback are ongoing challenges in all states. Leveraging stakeholders' personal stories of how opioids affected their lives helped propel state efforts.

Validation of a real-time PCR-based qualitative assay for the detection of methylated SEPT9 DNA in human plasma.

BACKGROUND: Epi proColon® is a new blood-based colorectal cancer (CRC) screening test designed to determine the methylation status of a promoter region of the SEPT9 (septin 9) gene in cell-free DNA isolated from plasma. We describe the analytical and clinical performance of the test. METHODS: Analytical performance at 4 testing laboratories included determination of limit of detection, precision, and reproducibility of the SEPT9 test. Clinical performance was evaluated in a prospective study by use of samples (n = 1544) from subjects enrolled in the PRESEPT clinical trial. Results were analyzed by comparison with colonoscopy, the reference standard. RESULTS: The limit of detection for methylated SEPT9 DNA was 7.8 pg/mL (95% CI 6-11 pg/mL) corresponding to <2 genome copies of methylated SEPT9 per milliliter of plasma. In the prospective clinical trial, sensitivity for all stages of CRC was 68% (95% CI 53%-80%) and for stage I-III CRC, 64% (48%-77%). Adjusted specificity, on the basis of negative colonoscopy findings, was 80.0% (78%-82%). SIGNIFICANCE: The Epi proColon test is a simple, real-time PCR-based assay for the detection of methylated SEPT9 DNA in blood that may provide a noninvasive CRC screening alternative for people noncompliant with current CRC screening guidelines.

Evaluation of a microarray-based genotyping assay for the rapid detection of cytochrome P450 2C19 *2 and *3 polymorphisms from whole blood using nanoparticle probes.

Numerous drugs such as clopidogrel have been developed to reduce coagulation or inhibit platelet function. The hepatic cytochrome P450 (CYP) pathway is involved in the conversion of clopidogrel to its active metabolite. A recent black-box warning was included in the clopidogrel package insert indicating a significant clinical link between specific CYP2C19 genetic variants and poor metabolism of clopidogrel. Of these variants, *2 and *3 are the most common and are associated with complete loss of enzyme activity. In patients who are carriers of a CYP2C19 *2 or *3 allele, the conversion of clopidogrel to its active metabolite may be reduced, which can lead to ischemic events and negative consequence for the patient. We examined the ability of the Verigene CLO assay (Nanosphere, Northbrook, IL) to identify CYP2C19 *2 and *3 polymorphisms in 1,286 unique whole blood samples. The Verigene CLO assay accurately identified homozygous and heterozygous *2 and *3 phenotypes with a specificity of 100% and a final call rate of 99.7%. The assay is fully automated and can produce a result in approximately 3.5 hours.