Marginal BH4 deficiencies, iNOS, and self-perpetuating oxidative stress in post-acute sequelae of Covid-19.

The treatment of post-acute sequelae of Covid-19 (PASC) has been informed primarily by symptomatic parallels with other chronic inflammatory syndromes. This manuscript takes a more systemic approach by examining how a marginal deficiency of tetrahydrobiopterin (BH4) resulting from mutations of the GCH1 (GTP cyclohydrolase 1) gene may result in the uncoupling of inducible Nitric Oxide Synthase (iNOS) early in the initial response of the innate immune system to SARS-CoV-2. The resulting production of superoxide instead of nitric oxide leads to a self-perpetuating cycle of oxidative stress with the potential to impair numerous metabolic processes and damage multiple organ systems. This marginal deficiency of BH4 may be exhibited by 30% or more of the patient population that have heterozygous or homozygous mutations of GCH1. As the cycle of oxidative stress continues, there is less BH4 available for other metabolic needs such as 1) resisting increased ferroptosis with its damage to organs, and 2) regulating the deactivation of the hyperinflammatory state. Finally, possible steps are proposed for clinical treatment of the hypothesized oxidative stress involved with PASC.

A high-stakes assessment approach to applied pharmacokinetics instruction.

OBJECTIVES: To identify instructional and assessment problems leading to pharmacy students' failure to retain pharmacokinetics abilities into the experiential year and develop an instructional methodology and abilities-based assessment tool to address the problem. METHODS: Pharmacokinetic instructional methods were assessed and an abilities-based assessment tool was developed and utilized as a requirement for curricular progression. Both the instructional methodology and the assessment tool were evaluated using abilities-based outcomes and faculty surveys. ASSESSMENT: Both instructional methods and assessment methods improved student pharmacokinetic skill performance in the direct patient-care environment. CONCLUSIONS: Continual assessment, modification, and implementation of teaching methods and the adoption of a high-stakes abilities-based assessment impacted student learning in a problem-based, integrated course.

Learning motivational interviewing: scripting a virtual patient.

OBJECTIVES: This article describes a written assignment for a first-year professional communication course to facilitate the understanding and mastery of motivational interviewing in dealing with patient ambivalence and resistance. The goal was to immerse students in how motivational interviewing differs from traditional biomedical counseling with regard to phrasing individual responses to the patient and managing the flow of interaction. METHODS: Students were required to write a script for a working prototype of the Auburn University Virtual Patient. The script had to specify the text for the virtual patient's comments, 2-5 possible responses for the student pharmacist to choose from, and multiple interactional paths representing motivational interviewing, biomedical counseling, and a mix of the 2. RESULTS: Student feedback and test results are reported. Qualitative analysis of written student feedback indicated that (1) the project took too much time because of the complexities of the computer procedures resulting from the Virtual Patient being a prototype, and (2) the computer procedures deflected attention from the critical thinking involved in writing the script. Quantitative item analysis of final examination results indicated that students scored an average one full-letter grade better on the questions about motivational interviewing than on the questions covering other topics. CONCLUSION: The scriptwriting assignment is a challenging exercise in assimilating the verbal skills necessary for using motivational interviewing in patient counseling. Many students exhibited greater interest in motivational interviewing, greater knowledge of why motivational interviewing is successful, greater facility with wording responses, and greater confidence in their ability to use motivational interviewing in the future. Because almost all students had negative reactions to the difficulty and time involved in making their scripts actually work with the virtual patient prototype, future assignments should delete this requirement.

Patient decision making: strategies for diabetes diet adherence intervention.

BACKGROUND: Patient self-care is critical in controlling diabetes and its complications. Lack of diet adherence is a particular challenge to effective diabetes intervention. The Transtheoretical Model (TTM) of Change, decision-making theory, and self-efficacy have contributed to successful tailoring of interventions in many target behaviors. OBJECTIVE: The purpose of this study was to develop a diagnostic tool, including TTM measures for the stages of change, decisional balance, and self-efficacy, that pharmacists involved in diabetes intervention can use for patients resistant to a diet regimen. METHODS: A questionnaire was developed through a literature review, interviews with diabetic patients, an expert panel input, and pretesting. Cross-sectional implementation of the questionnaire among a convenience sample of 193 type 1 and type 2 diabetic patients took place at 4 patient care sites throughout the southeastern United States. Validated measures were used to collect respondent self-report for the TTM variables and for demographic and diabetes history variables. Social desirability was also assessed. RESULTS: Relationships among TTM measures for diet adherence generally replicated those established for other target behaviors. Salient items were identified as potential facilitators (decisional balance pros) or barriers (decisional balance cons and self-efficacy tempting situations) to change. Social desirability exhibited a statistically significant relationship with patient report of diet adherence, with statistically significant differences in mean social desirability across race categories. CONCLUSIONS: The TTM measures for the stages of change, decisional balance, and self-efficacy are useful for making decisions on individually tailored interventions for diet adherence, with caution asserted about the potential of diabetes patients to self-report the target behavior in a socially desirable manner. Future research directions, implications, and limitations of the findings are also presented.