A Theoretical Framework for Conducting Psychiatric Mental Health Nursing Virtual Care & Research.

Despite rapid adoption and implementation, theoretical research considerations for virtual care (VC), defined simply as healthcare delivered using technology, are lacking across psychiatric mental health nursing (PMHN) scholarship. By adapting Hildegard Peplau's Interpersonal Relations Theory (IRT) and Media Richness Theory (MRT) using an intermodern and emancipatory knowing approach, a new framework was created for guiding modern PMHN VC research. Using this theoretical framework, readers can gain awareness of how the art and science of PMHN practice can be applied to VC scholarly endeavors in the modern healthcare space.

Clear integration of nursing and media theories to inform modern psychiatric mental health nursing virtual care and respective clinical vignetteDetails how the art and science of psychiatric mental health nursing can be applied to virtual care and researchFuture research applications regarding psychiatric mental health nursing virtual care are providedAmple review of interpersonal relations theory in psychiatric mental health nursing practice.

Trends of Opioid Use Disorder and Associated Factors in Hospitalized Patients With Arthritis.

Introduction Opioid use was primarily limited to acute pain, postsurgical care, and end of life care setting but now is the most prescribed medication for chronic pain. Arthritis is a chronic disease associated with chronic pain. Given limited options for pain relief in the patient population, these patients are often prescribed opioids and are at increased risk of opioid use disorder (OUD). Therefore, our study aimed to identify factors associated with OUD in patients with arthritis. Methods We analyzed hospitalized adult patients with arthritis with and without OUD using discharge data from National Inpatient Sample (NIS) over five years from January 1, 2010, to December 31, 2014. We looked at trends of OUD in hospitalized patients with arthritis and compared demographic and clinical characteristics of patients with and without OUD using Student's t-test and chi-square test. Multivariate analysis was also used to adjust for variables. Results A total of 21,396,252 arthritis hospitalizations were identified during the five-year study period among which 227,608 had OUD. The prevalence of OUD in arthritis hospitalization increased over the five-year period by 43%. After adjusting for other variables, mental health (OR 2.50 (2.43-2.58)), and substance use (OR 6.39 (6.14-6.66)) disorders were associated with increased odds of OUD. Conclusion The prevalence of OUD among patients with arthritis increased over the five-year study period. Mental health and substance use disorders were associated with increased odds of OUD. More studies are needed to explore alternative pain management options for arthritis patients particularly in those with mental health and substance use disorders.

Optimization of LpxC Inhibitor Lead Compounds Focusing on Efficacy and Formulation for High Dose Intravenous Administration.

LpxC inhibitors were optimized starting from lead compounds with limited efficacy and solubility and with the goal to provide new options for the treatment of serious infections caused by Gram-negative pathogens in hospital settings. To enable the development of an aqueous formulation for intravenous administration of the drug at high dose, improvements in both solubility and antibacterial activity in vivo were prioritized early on. This lead optimization program resulted in the discovery of compounds such as 13 and 30, which exhibited high solubility and potent efficacy against Gram-negative pathogens in animal infection models.

Discovery of Novel Inhibitors of LpxC Displaying Potent in Vitro Activity against Gram-Negative Bacteria.

UDP-3-O-((R)-3-hydroxymyristoyl)-N-glucosamine deacetylase (LpxC) is as an attractive target for the discovery and development of novel antibacterial drugs to address the critical medical need created by multidrug resistant Gram-negative bacteria. By using a scaffold hopping approach on a known family of methylsulfone hydroxamate LpxC inhibitors, several hit series eliciting potent antibacterial activities against Enterobacteriaceae and Pseudomonas aeruginosa were identified. Subsequent hit-to-lead optimization, using cocrystal structures of inhibitors bound to Pseudomonas aeruginosa LpxC as guides, resulted in the discovery of multiple chemical series based on (i) isoindolin-1-ones, (ii) 4,5-dihydro-6H-thieno[2,3-c]pyrrol-6-ones, and (iii) 1,2-dihydro-3H-pyrrolo[1,2-c]imidazole-3-ones. Synthetic methods, antibacterial activities and relative binding affinities, as well as physicochemical properties that allowed compound prioritization are presented. Finally, in vivo properties of lead molecules which belong to the most promising pyrrolo-imidazolone series, such as 18d, are discussed.

Comparison of the "contact biomechanics" of the intact and proximal row carpectomy wrist.

PURPOSE: The proximal row carpectomy (PRC) is a clinically useful motion-preserving procedure for various arthritides of the wrist. However, there are few studies on the "contact biomechanics" after PRC. The purpose of this study is to evaluate the contact biomechanics in terms of pressure, area, and contact location of the intact and PRC wrist. METHODS: Six fresh-frozen cadaver forearms were tested in neutral, 45 degrees of flexion, and 45 degrees of extension. In the intact wrist, Fuji UltraSuperLow pressure contact film was placed in the radioulnocarpal joint. The specimen was loaded to a total force of 200 N. We then performed a PRC, and the experiment was repeated using Fuji Low film. The film was scanned and analyzed with a customized MATLAB program. Multivariable analysis of variance with multiple contrast testing and Student's t-test were performed for statistics. RESULTS: In the intact wrist, scaphoid contact pressure averaged 1.4 megapascals (MPa), and lunate contact pressure averaged 1.3 MPa. In terms of contact location, scaphoid contact in the intact wrist significantly moved dorsal and ulnar in flexion and significantly moved volar and radial in extension. Lunate contact significantly moved dorsal in flexion. PRC wrist contact pressure was 3.8 times that of the intact wrist, and the contact area was approximately 26% that of the intact wrist. Lastly, in terms of the amount of contact translation after PRC, the capitate contact translated (7.5 mm) more than did the scaphoid contact (5.6 mm) and had about equal translation to that of the lunate (7.3 mm). CONCLUSIONS: Contact pressure increased significantly and contact area decreased significantly after PRC. There is significant contact translation after PRC (more than scaphoid translation but equal to lunate translation), which provides quantitative support of the theory that translational motion of the PRC may explain its good clinical outcomes.

Synthesis and Characterization of Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Antibacterial Activity against Gram-Negative Bacteria.

There is an urgent unmet medical need for novel antibiotics that are effective against a broad range of bacterial species, especially multidrug resistant ones. Tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) display potent activity against Gram-positive pathogens and no target-mediated cross-resistance with fluoroquinolones. We report our research efforts aimed at expanding the antibacterial spectrum of this class of molecules toward difficult-to-treat Gram-negative pathogens. Physicochemical properties (polarity and basicity) were considered to guide the design process. Dibasic tetrahydropyran-based compounds such as 6 and 21 are potent inhibitors of both DNA gyrase and topoisomerase IV, displaying antibacterial activities against Gram-positive and Gram-negative pathogens (Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii). Compounds 6 and 21 are efficacious in clinically relevant murine infection models.

Novel tetrahydropyran-based bacterial topoisomerase inhibitors with potent anti-gram positive activity and improved safety profile.

Novel antibacterial drugs that are effective against infections caused by multidrug resistant pathogens are urgently needed. In a previous report, we have shown that tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. During the course of our optimization program, lead compound 5 was deprioritized due to adverse findings in cardiovascular safety studies. In the effort of mitigating these findings and optimizing further the pharmacological profile of this class of compounds, we have identified a subseries of tetrahydropyran-based molecules that are potent DNA gyrase and topoisomerase IV inhibitors and display excellent antibacterial activity against Gram positive pathogens, including clinically relevant resistant isolates. One representative of this class, compound 32d, elicited only weak inhibition of hERG K(+) channels and hNaV1.5 Na(+) channels, and no effects were observed on cardiovascular parameters in anesthetized guinea pigs. In vivo efficacy in animal infection models has been demonstrated against Staphylococcus aureus and Streptococcus pneumoniae strains.

Design, synthesis, and characterization of novel tetrahydropyran-based bacterial topoisomerase inhibitors with potent anti-gram-positive activity.

There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase-topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K(+) channel block. On the other hand, analog 49e displayed lower hERG K(+) channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.