Exploring the impact of CYP2D6 and UGT2B7 gene-drug interactions, and CYP-mediated DDI on oxycodone and oxymorphone pharmacokinetics using physiologically-based pharmacokinetic modeling and simulation.

Oxycodone is one of the most commonly used opioids to treat moderate to severe pain. It is metabolized mainly by CYP3A4 and CYP2D6, while only a small fraction of the dose is excreted unchanged into the urine. Oxymorphone, the metabolite primarily formed by CYP2D6, has a 40- to 60-fold higher mu-opioid receptor affinity than the parent compound.

The Association of Serotonin Toxicity with Combination Linezolid-Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis.

Linezolid (LZD) has a longstanding reported association with the onset of serotonin toxicity (ST), secondary to drug-drug interactions with serotoninergic agents. There have been no conclusive data supporting the incidence or contributing risk factors to date. The study evaluated the incidence of ST in patients treated with LZD and serotonergic agents concomitantly versus LZD alone.

Pharmacogenetic Testing in a 70-Year-Old Woman with Polypharmacy and Multiple Comorbidities: A Case Report.

BACKGROUND Comorbidities and polypharmacy are difficult to manage, as polypharmacy hinders identification and prevention of medication-related problems. Risk for adverse drug events (ADEs) can be minimized through pharmacogenomic (PGx) testing and related therapeutic adjustments. CASE REPORT A 70-year-old woman with comorbidities and medications enrolled in the Program of All-inclusive Care for the Elderly presented with left lower extremity (LLE) pain, generalized weakness, and major depressive disorder.

Colombian Sustainability Perspective on Fused Deposition Modeling Technology: Opportunity to Develop Recycled and Biobased 3D Printing Filaments.

In the context of the preservation of natural resources, researchers show a growing interest in developing eco-friendly materials based on recycled polymers and natural fiber biocomposites to minimize plastic and agroindustrial waste pollution. The development of new materials must be integrated within the circular economy concepts to guarantee sustainable production. In parallel, fused deposition modeling, an additive manufacturing technology, provides the opportunity to use these new materials in an efficient and sustainable manner.

Multidrug Interactions: Why Do They Occur and How to Handle?

A nonoptimized medication therapy (NOMT) event is an iatrogenic hazard or incident associated with medications and is a leading cause of death, serious injury, and illness. NOMT events are often related to multidrug interactions in patients with polypharmacy. In these patients, NOMT events can be avoided by using advanced clinical decision support systems and clinical interventions such as separating the time of administration of certain drugs during the day.

Case Report: Performing a Medication Safety Review Assisted by Pharmacogenomics to Explain a Prescribing Cascade Resulting in a Patient Fall.

Pharmacotherapy for major depressive disorder (MDD) typically consists of trial-and-error and clinician preference approaches, where patients often fail one or more antidepressants before finding an optimal regimen. Pharmacogenomics (PGx) can assist in prescribing appropriate antidepressants, thereby reducing the time to MDD remission and occurrence of adverse drug events. Since many antidepressants are metabolized by and/or inhibit cytochrome P450 enzymes (e.

Recycling of Bottle Grade PET: Influence of HDPE Contamination on the Microstructure and Mechanical Performance of 3D Printed Parts.

As part of a project that aims to provide people with disabilities with simple assistive devices in Colombia, the possibility of creating a PET filament that can be printed by Fused Deposition Modelling (FDM) from beverage bottle waste was investigated, with the aim to remain as simple as possible in terms of plastic collection, sorting, processing, and printing. Recycled PET filaments were thus produced by extrusion from collected PET bottles, with the potential addition of HDPE, which comes from caps and rings. The microstructure, mechanical performance, and printing quality of parts produced with these filaments were investigated in comparison to commercial PET virgin and recycled filaments.

Utilizing Pharmacogenomics Results to Determine Opioid Appropriateness and Improve Pain Management in a Patient with Osteoarthritis.

The opioid epidemic in the United States has exposed the need for providers to limit opioid dispensing and identify at-risk patients prior to prescribing opioids. With pharmacogenomic testing, clinicians can analyze hundreds of medications-including commonly prescribed opioids-against genetic results to understand and predict risk and response. Moreover, knowledge of genotypic variants and altered function can help decrease trial and error prescribing, identify patients at-risk for adverse drug events, and improve pain control.

Pharmacist-driven interventions to de-escalate urinary antimuscarinics in the Programs of All-Inclusive Care for the Elderly.

Background: Given associations with serious cognitive and physical adverse effects (e.g., dementia, falls), strong anticholinergics, like urinary antimuscarinics (UAMs), should be avoided in older adults.

Pharmacogenomics and Drug-Induced Phenoconversion Informed Medication Safety Review in the Management of Pain Control and Quality of Life: A Case Report.

Utilizing pharmacogenomics (PGx) and integrating drug-induced phenoconversion to guide opioid therapies could improve the treatment response and decrease the occurrence of adverse drug events. Genetics contribute to the interindividual differences in opioid response. The purpose of this case report highlights the impact of a PGx-informed medication safety review, assisted by a clinical decision support system, in mitigating the drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively) that increase the risk of an inadequate drug response and adverse drug events (ADEs).

Sustainable polyesters via direct functionalization of lignocellulosic sugars.

The development of sustainable plastics from abundant renewable feedstocks has been limited by the complexity and efficiency of their production, as well as their lack of competitive material properties. Here we demonstrate the direct transformation of the hemicellulosic fraction of non-edible biomass into a tricyclic diester plastic precursor at 83% yield (95% from commercial xylose) during integrated plant fractionation with glyoxylic acid. Melt polycondensation of the resulting diester with a range of aliphatic diols led to amorphous polyesters (M = 30-60 kDa) with high glass transition temperatures (72-100 °C), tough mechanical properties (ultimate tensile strengths of 63-77 MPa, tensile moduli of 2,000-2,500 MPa and elongations at break of 50-80%) and strong gas barriers (oxygen transmission rates (100 µm) of 11-24 cc m day bar and water vapour transmission rates (100 µm) of 25-36 g m day) that could be processed by injection moulding, thermoforming, twin-screw extrusion and three-dimensional printing.

Revisiting conclusions on the empiric segmentation of high-risk patients.

The authors provide feedback on generalizations made regarding interventions for high-risk populations in previous research.

A functional approach towards the design, development, and test of an affordable dynamic prosthetic foot.

Humanitarian actors involved in physical rehabilitation, such as the International Committee of the Red Cross (ICRC), usually provide their beneficiaries with lower-limb prostheses comprising Solid Ankle Cushion Heel (SACH) feet as these are considered appropriate (price, durability, low profile to fit a majority of patients, appearance) and reliable for all ambulation levels. However, individuals in low-resource settings having higher ambulation abilities would greatly benefit from dynamic prosthetic feet with improved biomechanics and energy storage and release. Some attempts tried to address this increasing need (e.

Community Masks - from an Emergency Solution to an Innovation Booster for the Textile Industry.

The COVID-19 pandemic resulted in shortages of personal protective equipment and medical devices in the initial phase. Agile small and medium-sized enterprises from regional textile industries reacted quickly. They delivered alternative products such as textile-based community masks in collaboration with industrial partners and research institutes from various sectors.

On the durability of surgical masks after simulated handling and wear.

After the spread of COVID-19, surgical masks became highly recommended to the public. They tend to be handled and used multiple times, which may impact their performance. To evaluate this risk, surgical masks of Type IIR were submitted to four simulated treatments: folding, ageing with artificial saliva or sweat and washing cycles.

Illustrative and historic cases of phenoconversion.

Intersubject variability in drug response, whether related to efficacy or toxicity, is well recognized clinically. Over the years, drug selection from our pharmacologic armamentarium has moved from providers' preferred choices to more personalized treatments as clinicians' decisions are guided by data from clinical trials. Since the advent of more accessible and affordable pharmacogenomic (PGx) testing, the promise of precise pharmacotherapy has been made.

Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics.

The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein expression levels of 16 major CYP450 isoforms in tissue obtained from nine human organ donors in seven subsections of the small intestine, i.

Use of Drug Claims Data and a Medication Risk Score to Assess the Impact of CYP2D6 Drug Interactions among Opioid Users on Healthcare Costs.

Cytochrome P450 2D6 (CYP2D6) activity is highly variable due to several factors, including genetic polymorphisms and drug-drug-gene interactions. Hydrocodone, oxycodone, codeine, and tramadol the most commonly prescribed CYP2D6-activated opioids for pain. However, the co-administration of CYP2D6 interacting drugs can modulate CYP2D6-medicated activation of these opioids, affecting drug analgesia, effectiveness, and safety, and can impact healthcare costs.

Quantifying Anticholinergic Burden and Sedative Load in Older Adults with Polypharmacy: A Systematic Review of Risk Scales and Models.

Background: Patients taking medication with high anticholinergic and sedative properties are at increased risk of experiencing poor cognitive and physical outcomes. Therefore, precise quantification of the cumulative burden of their drug regimen is advisable. There is no agreement regarding which scale to use to simultaneously quantify the burden associated with medications.

Cannabis Dopaminergic Effects Induce Hallucinations in a Patient with Parkinson's Disease.

Cannabis products that contain the tetrahydrocannabinol (THC) cannabinoid are emerging as promising therapeutic agents for the treatment of medical conditions such as chronic pain. THC elicits psychoactive effects through modulation of dopaminergic neurons, thereby altering levels of dopamine in the brain. This case report highlights the complexity associated with medicinal cannabis and the health risks associated with its use.

Pharmacist-Led Medication Evaluation Considering Pharmacogenomics and Drug-Induced Phenoconversion in the Treatment of Multiple Comorbidities: A Case Report.

Pharmacogenomic (PGx) information can guide drug and dose selection, optimize therapy outcomes, and/or decrease the risk of adverse drug events (ADEs). This report demonstrates the impact of a pharmacist-led medication evaluation, with PGx assisted by a clinical decision support system (CDSS), of a patient with multiple comorbidities. Following several sub-optimal pharmacotherapy attempts, PGx testing was recommended.

Contribution of CYP2D6 Functional Activity to Oxycodone Efficacy in Pain Management: Genetic Polymorphisms, Phenoconversion, and Tissue-Selective Metabolism.

Oxycodone is a widely used opioid for the management of chronic pain. Analgesic effects observed following the administration of oxycodone are mediated mostly by agonistic effects on the μ-opioid receptor. Wide inter-subject variability observed in oxycodone efficacy could be explained by polymorphisms in the gene coding for the μ-opioid receptor ().

Association of the MedWise Risk Score with health care outcomes.

Objectives: Older patients are especially vulnerable to drug-related problems due to multiple prescription drugs, which increases their risk of drug-drug interactions and adverse drug events (ADEs). This study aimed to examine outcomes associated with the MedWise Risk Score (MRS) in a Medicare Part D population, including total medical expenditures, ADEs, falls, mortality, emergency department (ED) visits, hospital admissions, and length of stay (LOS).

Study Design: Retrospective observational study.

Classification and Assessment of Medication Risk in the Elderly (CARE): Use of a Medication Risk Score to Inform Patients' Readmission Likelihood after Hospital Discharge.

Existing risk tools that identify patients at high risk of medication-related iatrogenesis are not sufficient to holistically evaluate a patient's entire medication regimen. This study used a novel medication risk score (MRS) which holistically evaluates medication regimens and provides actionable solutions. The main purpose of this study was to quantify adults ≥ 65 years with a high medication risk burden using the MRS and secondarily, appraise MRS association with hospital readmission.