Medication Exposure Patterns in Primary Care Patients Prescribed Pharmacogenetically Actionable Opioids

Current approaches to assessing medication exposure fail to capture the complexity of the phenomenon and the context in which it occurs. This study’s purpose was to develop a typology of subgroups of patients who share common patterns of medication exposure. To create the typology, we used an exemplar sample of 30 patients in a large public healthcare system who had been prescribed the pharmacogenetically actionable opioids codeine or tramadol. Data related to medication exposure were drawn from large data repositories. Using a person-oriented qualitative approach, eight subgroups of patients who shared common patterns of medication exposure were identified. The subgroups had one of five opioid prescription patterns (i.e., singular, episodic, switching, sustained, multiplex), and one of three types of primary foci of medical care (i.e., pain, comorbidities, both). The findings reveal medication exposure patterns that are dynamic, multidimensional, and complex, and the typology offers an innovative approach to assessing medication exposure

CYP2D6 drug-gene and drug-drug-gene interactions among patients prescribed pharmacogenetically actionable opioids

Purpose When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain. Methods We used three data sources: (1) six months of electronic health record data on the number and types of medications prescribed to each patient; (2) each patient's CYP2D6 pharmacogenotype, and (3) published data on known CYP2D6 gene-drug and drug-drug-gene interactions. Results Ten patients (33%) had possible drug-gene or drug-drug-gene interactions. Five patients had CYP2D6 drug-gene interactions indicating they were not good candidates for codeine or tramadol. In addition, five patients had potential CYP2D6 drug-drug-gene interactions with either codeine or tramadol. Conclusion Our findings from this exploratory study underscores the importance of assessing and accounting for drug-gene and drug-drug-gene interactions in patients prescribed codeine or tramadol

Denitrification bioreactor trial in the Russell River catchment of the Wet Tropics: final report

Dissolved inorganic nitrogen (DIN) in runoff from agricultural land is considered to have a significant detrimental impact on the Great Barrier Reef (GBR). Losses of DIN to runoff can be reduced by good agricultural practices, but they cannot be eliminated entirely in the Wet Tropics due to the need for adequate nitrogen supply to crops, the high solubility of DIN, particularly nitrate, and high rainfall. Thus, it is inevitable that DIN concentrations are higher in runoff from agricultural land than from forested areas. Some of this DIN is removed from the water as it moves through aquifers, creeks, rivers, and wetlands on its way to the sea, through the process of microbial denitrification. Denitrification involves the conversion of nitrate and nitrite (NOx-N) to dinitrogen (N2) gas, which is lost to the atmosphere. Denitrification requires NOx-N, organic matter, and low oxygen concentration. Wetlands provide these conditions, so DIN concentrations decline in water moving through them. Similarly, denitrifying bioreactors are designed to treat water by passing it through a porous organic material, typically woodchips. The woodchips provide organic matter for the microorganisms, which in turn lower the oxygen concentration, providing ideal conditions for denitrification. Denitrifying bioreactors are now widely used to remove the NOx-N component of DIN from agricultural runoff water elsewhere, but they have not yet been evaluated in the Wet Tropics. The Wet Tropics pose a challenge for efficacy due to the large volumes of water moving through the landscape. The objective of this project was “to establish the effectiveness of denitrifying bioreactors as a remediation technology for excess DIN in agricultural runoff within the Babinda Swamp Drainage Area (BSDA) of the Russell catchment”. The Russell River exports a disproportionate amount of DIN to the GBR lagoon because of the high rainfall and high proportion of agriculture, mostly sugarcane, in its catchment

Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin

Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation after hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally nonequivalent. We have investigated the functional and redox properties of Hb–Hp complexes prepared using commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of ~0.9 μM−1 s−1, irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO2 autoxidation by dissociating Hb tetramers into dimers, the rate observed for these bound dimers is three- to fourfold slower than that of Hb dimers free in solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below detectable levels. Intrinsic redox potentials (E1/2) of the ferric/ferrous pair of each Hb–Hp complex are similar, varying from +54 to +59 mV (vs NHE), and are essentially the same as reported by us previously for Hb–Hp complexes prepared from unfractionated Hp. All Hb–Hp complexes generate similar high amounts of ferryl Hb after exposure to hydrogen peroxide. Electron paramagnetic resonance data indicate that the yields of protein-based radicals during this process are approximately 4 to 5% and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions examined are equivalent to one another with respect to Hb binding and associated stability and redox properties and that this result should be taken into account in the design of phenotype-specific Hp therapeutics aimed at countering Hb-mediated vascular disease

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Alpha-hemoglobin stabilizing protein (AHSP) markedly decreases the redox potential and reactivity of alpha subunits of human HbA with hydrogen peroxide

Background: AHSP modifies redox properties of bound α subunits. Results: Isolated hemoglobin subunits exhibit significantly different redox properties compared to HbA. A significant decrease in the reduction potential of α subunits bound to AHSP results in preferential binding of ferric α. Conclusion: AHSP:α subunit complexes do not participate in ferric-ferryl heme redox cycling. Significance: AHSP binding to α subunits inhibits subunit pseudoperoxidase activity

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Transport through a strongly coupled graphene quantum dot in perpendicular magnetic field

We present transport measurements on a strongly coupled graphene quantum dot in a perpendicular magnetic field. The device consists of an etched single-layer graphene flake with two narrow constrictions separating a 140 nm diameter island from source and drain graphene contacts. Lateral graphene gates are used to electrostatically tune the device. Measurements of Coulomb resonances, including constriction resonances and Coulomb diamonds prove the functionality of the graphene quantum dot with a charging energy of around 4.5 meV. We show the evolution of Coulomb resonances as a function of perpendicular magnetic field, which provides indications of the formation of the graphene specific 0th Landau level. Finally, we demonstrate that the complex pattern superimposing the quantum dot energy spectra is due to the formation of additional localized states with increasing magnetic field.Comment: 6 pages, 4 figure