Pharmacogenomic Considerations for Anticoagulant Prescription in Patients with Hereditary Haemorrhagic Telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia that commonly results in bleeding but with frequent indications for therapeutic anticoagulation. Our aims were to advance the understanding of drug-specific intolerance and evaluate if there was an indication for pharmacogenomic testing. Genes encoding proteins involved in the absorption, distribution, metabolism, and excretion of warfarin, heparin, and direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran were identified and examined. Linkage disequilibrium with HHT genes was excluded, before variants within these genes were examined following whole genome sequencing of general and HHT populations. The 44 genes identified included 5/17 actionable pharmacogenes with guidelines. The 76,156 participants in the Genome Aggregation Database v3.1.2 had 28,446 variants, including 9668 missense substitutions and 1076 predicted loss-of-function (frameshift, nonsense, and consensus splice site) variants, i.e., approximately 1 in 7.9 individuals had a missense substitution, and 1 in 71 had a loss-of-function variant. Focusing on the 17 genes relevant to usually preferred DOACs, similar variant profiles were identified in HHT patients. With HHT patients at particular risk of haemorrhage when undergoing anticoagulant treatment, we explore how pre-emptive pharmacogenomic testing, alongside HHT gene testing, may prove beneficial in reducing the risk of bleeding and conclude that HHT patients are well placed to be at the vanguard of personalised prescribing.

Determination of anabasine, anatabine, and nicotine biomarkers in wastewater by enhanced direct injection LC-MS/MS and evaluation of their in-sewer stability.

Wastewater-based epidemiology (WBE) has been used to estimate tobacco use in the population. However, the increased use of nicotine replacement therapies and e-cigarettes contributes to the load of nicotine metabolites in wastewater, causing over-estimation of tobacco use if nicotine metabolites were used in WBE back-estimation. This study aims to develop a rapid method for determining the tobacco-specific biomarkers, anabasine and anatabine, in wastewater and to evaluate their in-sewer stability for better estimation of tobacco use by WBE. An enhanced direct injection LC-MS/MS was developed to quantify anabasine and anatabine as well as nicotine biomarkers (nicotine, cotinine and hydroxycotinine). The method was optimal when wastewater was filtered through 0.2 µm RC syringe filters and a pre-conditioned SPE cartridge (Oasis HLB 1 cc, 30 mg) before 50 µL was injected into the LC-MS/MS system. Limits of quantification varied between 2.7 and 54.9 ng/L with recoveries from 76% to 103% for all five compounds. In sewer reactors, anabasine and anatabine were less stable than cotinine and hydroxycotinine. They were more stable in the gravity sewer reactor with <20% loss in 12 h than in the rising main sewer reactor with ~30% loss in the same period. We then applied the new method to 42 daily wastewater influent samples collected from an Australian wastewater treatment plant. The five biomarkers were detected in all samples with concentrations ranging from 9.2 to 7430 ng/L. All five compounds were positively correlated with one another. Our results suggested a high throughput analytical method for feasible application in anabasine and anatabine as biomarkers of tobacco use in routine wastewater monitoring.

The added value of establishing a lexicon to help inform, compare, and better understand the implementation of policy, systems, and environmental change strategies in Supplemental Nutrition Assistance Program Education.

Categorization of terms/concepts/constructs that allows for better understanding and comparison of public health interventions is often lacking in program implementation and evaluation. A classification system such as a lexicon, when used appropriately, can help address this need. The present narrative describes a lexicon of policy, systems, and environmental change strategies (PSEs) that was developed and prototyped to aid local implementation of Supplemental Nutrition Assistance Program Education (SNAP-Ed) interventions in obesity prevention. The lexicon was reviewed and refined by a panel of experts who provided iterative feedback on the system's scope and utility. To develop the lexicon, a team from the local health department: (i) conducted an inventory (community context scan) of SNAP-Ed PSEs implemented in Los Angeles County during 2010-2015; (ii) assessed commonalities among PSEs that were translated into "index factors" to contextualize terms/concepts/constructs relevant to SNAP-Ed services planning; and (iii) convened a panel of experts to review and test the classification system for quality and usability. In the latter activity, the panel reviewed the terms/concepts/constructs within the context of two geographical areas and by the selected PSEs. The final version of the lexicon organized the terms/concepts/constructs of the local SNAP-Ed PSEs into overarching categories, so they can be compared/assessed by type, content, and/or impact. The goal of the project was to create a classification system that can help facilitate meaningful communications among program implementers, evaluators, and community stakeholders. The lexicon has practical implications and potential applications for other jurisdictions interested in reducing obesity rates through SNAP-Ed PSEs.

Hearing outcome of laser stapedotomy minus prosthesis (STAMP) versus conventional laser stapedotomy.

OBJECTIVE: The objective of this study was to compare short-and long-term hearing outcomes for patients undergoing primary laser stapedotomy minus prosthesis (STAMP) versus conventional laser stapedotomy. STUDY DESIGN: We conducted a retrospective case review of 167 consecutive patients from 1993 to 2002. SETTING: Otology/neurotology tertiary referral center. PATIENTS: We studied those with clinical otosclerosis without previous otologic surgery. INTERVENTIONS: Patients with otosclerosis confined to the fissula ante fenestram underwent STAMP. Patients with more extensive otosclerosis or anatomic contraindications to STAMP underwent standard laser stapedotomy. MAIN OUTCOME MEASURES: Pure-tone audiometry was performed before surgery, postoperatively, and on routine follow-up examination. RESULTS: Of the 183 ears in 167 patients, 128 (67.1%) underwent laser stapedotomy and 55 (32.98%) underwent STAMP. The STAMP mean air-bone gap (ABG) closed from a preoperative value of 22 dB (standard deviation [SD], 10 dB) to 6 dB (SD, 7 dB) on average follow up of 778 days. In 128 laser stapedotomy patients with an average follow up of 747 days, the preoperative mean ABG closed from 27 dB (SD, 10 dB) to 8 dB (SD, 7 dB). There was a trend toward improvement in high-frequency air conduction thresholds after STAMP versus worsening of high-frequency thresholds in the conventional stapedotomy group. There was a statistically significant improvement in most recent postoperative high-frequency (6000-8000 Hz) air conduction thresholds in the STAMP patients compared with patients who underwent conventional laser stapedotomy. CONCLUSION: Laser STAMP, when used for isolated anterior footplate otosclerosis, provides excellent high-frequency hearing, yields lasting results similar to conventional laser stapedotomy, and has a low incidence of refixation necessitating revision surgery.