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The role of a pharmacy residency program in global health: Establishing pediatric clinical pharmacy services in a Malawian hospital
No full textPurpose: To describe the establishment of pediatric clinical pharmacy services in a Malawian hospital as part of a pharmacy residency program\u27s engagement in global health. Summary: While pharmacy is expanding its role in global health through the introduction of international advanced pharmacy practice experience (APPE) rotations at US schools of pharmacy, international experiences for pharmacy residents are currently very limited. Such programs are advantageous for pharmacists planning for a career in public or global health, and there is also great opportunity for clinical pharmacists to work with international partners for professional development and to help advance pharmacy practice. The University of North Carolina at Chapel Hill Eshelman School of Pharmacy recently expanded its international APPE rotation in Malawi into the postgraduate training space through creation of a pediatric pharmacy residency training program, with the specific aim of working with partners in Malawi to introduce pediatric pharmacy services at Kamuzu Central Hospital. As this was the first time there was a pharmacist involved in patient care on the pediatric wards, the focus for the participating pharmacy resident was on establishing a positive relationship with the medical team through providing high-quality collaborative patient care for the pediatric population. In addition to working to establish pediatric clinical pharmacy services, the resident further contributed to sustainable improvements in pediatric patient care by identifying areas for quality improvement. We discuss several considerations for the successful implementation of international experiences and their impact on participating residents. Conclusion: Pharmacy has an opportunity to build on the success of international APPE rotations and expand postgraduate offerings. Through collaboration with other institutions already involved in global health and identifying international rotation sites, residency programs across the country can create similarly beneficial global health experiences for their pharmacy residents
Implementation and Evaluation of Two Nudges in a Hospital’s Electronic Prescribing System to Optimise Cost-Effective Prescribing
No full textProviding healthcare workers with cost information about the medications they prescribe can influence their decisions. The current study aimed to analyse the impact of two nudges that presented cost information to prescribers through a hospital’s electronic prescribing system. The nudges were co-created by the research team: four behavioural scientists and the lead hospital phar-macist. The nudges were rolled out sequentially. The first nudge provided simple cost information (percentage cost-difference between two brands of mesalazine: Asacol® and Octasa®). The second nudge provided information about the potential annual cost savings if the cheaper medication were selected across the National Health Service. Neither nudge influenced prescribing. Prescribing of Asacol® and Octasa® at baseline and during the implementation of the first nudge did not differ (at p ≥ 0.05), nor was there a difference between the first nudge and second (at p ≥ 0.05). Although these nudges were not effective, notable administrative barriers were overcome, which may inform future research. For example, although for legal reasons the cost of medicine cannot be displayed, we were able to present aggregated cost information to the prescribers. Future research could reveal more behavioural factors that facilitate medication optimisation
Policy landscapes on human genome editing: a perspective from Latin America
No full textPolicy landscapes are instruments that identify national regulations on human genome editing (HGE). After examining their ethical and political assumptions, we highlight their limitations and effects for Latin America. We suggest creating other landscapes, such as focusing on processes and drawing attention to potential ‘circuits of use’ within and across borders
Retrospective evaluation of an intervention based on training sessions to increase the use of control charts in hospitals
No full textBackground Statistical process control charts (SPCs) distinguish signal from noise in quality and safety metrics and thus enable resources to be targeted towards the most suitable actions for improving processes and outcomes. Nevertheless, according to a recent study, SPCs are not widely used by hospital boards in England. To address this, an educational training initiative with training sessions lasting less than one and a half days was established to increase uptake of SPCs in board papers. This research evaluated the impact of the training sessions on the inclusion of SPCs in hospital board papers in England. Methods We used a non-randomised controlled before and after design. Use of SPCs was examined in 40 publicly available board papers across 20 hospitals; 10 intervention hospitals and 10 control hospitals matched using hospital characteristics and time-period. Zero-inflated negative binomial regression models and t-tests compared changes in usage by means of a difference in difference approach. Results Across the 40 board papers in our sample, we found 6287 charts. Control hospitals had 9/1585 (0.6%) SPCs before the intervention period and 23/1900 (1.2%) after the intervention period, whereas intervention hospitals increased from 89/1235 (7%) before to 328/1567 (21%) after the intervention period; a relative risk ratio of 9 (95% CI 3 to 32). The absolute difference in use of SPCs was 17% (95% CI 6% to 27%) in favour of the intervention group. Conclusions The results suggest that a scalable educational training initiative to improve use of SPCs within organisations can be effective. Future research could aim to overcome the limitations of observational research with an experimental design or seek to better understand mechanisms, decision-making and patient outcomes
Pharmacophore modeling for biological targets with high flexibility: LXRβ case study
No full textMany biological targets are characterized by high binding pocket flexibility posing a challenge in identifying important ligand binding features. Liver X receptors (LXRs) are members of the nuclear hormone receptor super family. Although several X-ray structures for LXRβ bound ligands are available, differences in ligands’ binding poses and interactions in the ligand binding pocket causes a challenge in identifying general elements of ligand binding. In this study, we used several LXR X-ray structures and known LXR ligands to study how LXRβ ligands interact with the LXRβ receptor. Using this information, we generated several pharmacophore models that represents important chemical features necessary for LXR binding and activation. Our results show that generating pharmacophore models based on a combined approach of multiple ligands alignments and considering the ligands’ binding coordinates yielded the best results. The generated pharmacophore model will be useful for future ligand discovery of LXRβ modulators using virtual screening
Evaluation of Potential Anti-Hepatitis a Virus 3C Protease Inhibitors Using Molecular Docking
No full textHepatitis A virus (HAV) infection is a major cause of acute hepatitis worldwide and occasionally causes acute liver failure and can lead to death in the absence of liver transplantation. Although HAV vaccination is available, the prevalence of HAV vaccination is not adequate in some countries. Additionally, the improvements in public health reduced our immunity to HAV infection. These situations motivated us to develop potentially new anti-HAV therapeutic options. We carried out the in silico screening of anti-HAV compounds targeting the 3C protease enzyme using the Schrodinger Modeling software from the antiviral library of 25,000 compounds to evaluate anti-HAV 3C protease inhibitors. Additionally, in vitro studies were introduced to examine the inhibitory effects of HAV subgenomic replicon replication and HAV HA11-1299 genotype IIIA replication in hepatoma cell lines using luciferase assays and real-time RT-PCR. In silico studies enabled us to identify five lead candidates with optimal binding interactions in the active site of the target HAV 3C protease using the Schrodinger Glide program. In vitro studies substantiated our hypothesis from in silico findings. One of our lead compounds, Z10325150, showed 47% inhibitory effects on HAV genotype IB subgenomic replicon replication and 36% inhibitory effects on HAV genotype IIIA HA11-1299 replication in human hepatoma cell lines, with no cytotoxic effects at concentrations of 100 μg/mL. The effects of the combination therapy of Z10325150 and RNA-dependent RNA polymerase inhibitor, favipiravir on HAV genotype IB HM175 subgenomic replicon replication and HAV genotype IIIA HA11-1299 replication showed 64% and 48% inhibitory effects of HAV subgenomic replicon and HAV replication, respectively. We identified the HAV 3C protease inhibitor Z10325150 through in silico screening and confirmed the HAV replication inhibitory activity in human hepatocytes. Z10325150 may offer the potential for a useful HAV inhibitor in severe hepatitis A
Identification of Novel Mitochondrial Pyruvate Carrier Inhibitors by Homology Modeling and Pharmacophore-Based Virtual Screening
No full textThe mitochondrial pyruvate carrier (MPC) is an inner-mitochondrial membrane protein complex that has emerged as a drug target for treating a variety of human conditions. A heterodimer of two proteins, MPC1 and MPC2, comprises the functional MPC complex in higher organisms; however, the structure of this complex, including the critical residues that mediate binding of py-ruvate and inhibitors, remain to be determined. Using homology modeling, we identified a putative substrate-binding cavity in the MPC dimer. Three amino acid residues (Phe66 (MPC1) and Asn100 and Lys49 (MPC2)) were validated by mutagenesis experiments to be important for substrate and inhibitor binding. Using this information, we developed a pharmacophore model and then per-formed a virtual screen of a chemical library. We identified five new non-indole MPC inhibitors, four with IC50 values in the nanomolar range that were up to 7-fold more potent than the canonical inhibitor UK-5099. These novel compounds possess drug-like properties and complied with Lipinski’s Rule of Five. They are predicted to have good aqueous solubility, oral bioavailability, and metabolic stability. Collectively, these studies provide important information about the structure-function relationships of the MPC complex and for future drug discovery efforts targeting the MPC
Impact of the first wave of COVID-19 on the health and psychosocial well-being of Māori, Pacific Peoples and New Zealand Europeans living in aged residential care
No full textObjective: To investigate the impact of New Zealand\u27s (NZ) first wave of COVID-19, which included a nationwide lockdown, on the health and psychosocial well-being of Māori, Pacific Peoples and NZ Europeans in aged residential care (ARC). Methods: interRAI assessments of Māori, Pacific Peoples and NZ Europeans (aged 60 years and older) completed between 21/3/2020 and 8/6/2020 were compared with assessments of the same ethnicities during the same period in the previous year (21/3/2019 to 8/6/2019). Physical, cognitive, psychosocial and service utilisation indicators were included in the bivariate analyses. Results: A total of 538 Māori, 276 Pacific Peoples and 11,322 NZ Europeans had an interRAI assessment during the first wave of COVID-19, while there were 549 Māori, 248 Pacific Peoples and 12,367 NZ Europeans in the comparative period. Fewer Māori reported feeling lonely (7.8% vs. 4.5%, p = 0.021), but more NZ Europeans reported severe depressive symptoms (6.9% vs. 6.3%, p = 0.028) during COVID-19. Lower rates of hospitalisation were observed in Māori (7.4% vs. 10.9%, p = 0.046) and NZ Europeans (8.1% vs. 9.4%, p \u3c 0.001) during COVID-19. Conclusions: We found a lower rate of loneliness in Māori but a higher rate of depression in NZ European ARC populations during the first wave of COVID-19. Further research, including qualitative studies with ARC staff, residents and families, and different ethnic communities, is needed to explain these ethnic group differences. Longer-term effects from the COVID-19 pandemic on ARC populations should also be investigated
Emerging Role of Nuclear Receptors for the Treatment of NAFLD and NASH
No full textNon‐alcoholic fatty liver (NAFLD) over the past years has become a metabolic pandemic linked to a collection of metabolic diseases. The nuclear receptors ERRs, REV‐ERBs, RORs, FXR, PPARs, and LXR are master regulators of metabolism and liver physiology. The characterization of these nuclear receptors and their biology has promoted the development of synthetic ligands. The possibility of targeting these receptors to treat NAFLD is promising, as several compounds includ-ing Cilofexor, thiazolidinediones, and Saroglitazar are currently undergoing clinical trials. This review focuses on the latest development of the pharmacology of these metabolic nuclear receptors and how they may be utilized to treat NAFLD and subsequent comorbidities
Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis
No full textBackground: Telavancin is a lipoglycopeptide antibiotic with limited pharmacokinetic data to guide drug dosing in patients receiving haemodialysis. Objectives: This study characterized telavancin pharmacokinetics in patients receiving haemodialysis. Patients and methods: This was a Phase IV, prospective, open-label, single-centre, crossover pharmacokinetic study (ClinicalTrials.gov: NCT02392208). Eight subjects with end-stage kidney disease requiring maintenance haemodialysis (mean ± SD: 47 ± 20 years, 69.5 ± 17.1 kg) received 5 mg/kg telavancin IV 3 h before starting a 3.5 hour haemodialysis treatment with a high-permeability haemodialyser (haemodialysis period). After a 14 day washout period, a second 5 mg/kg dose was administered post-haemodialysis (control period). Telavancin plasma concentrations were measured over a 2 day period after each dose and non-compartmental pharmacokinetic analyses were performed. Results: The geometric mean (GM) of telavancin overall clearance was 11.2 mL/h/kg (intrinsic clearance and dialytic clearance) in the haemodialysis period and 5.9 mL/h/kg (off-haemodialysis clearance) in the control period [GM ratio (GMR) = 1.89; 90% CI: 1.70–2.10; P \u3c 0.01]. The GM t1=2 was 13.1 h when haemodialysis occurred 3 h post-dosing in the haemodialysis period but extended to 20.9 h with post-haemodialysis dosing in the control period (GMR = 0.63; 90% CI: 0.54–0.73; P \u3c 0.01). The GM of telavancin plasma concentrations removed by haemodialysis was 27.7%. The GMR of peak plasma concentration and volume of distribution of the haemodialysis period and the control period were 0.88 (90% CI: 0.79–0.98; P = 0.08) and 1.17 (90% CI: 1.05–1.30; P = 0.048), respectively. Conclusions: Haemodialysis with high-permeability haemodialysers removes telavancin considerably (~1=3 of body load). Telavancin 5 mg/kg every 48 h post-haemodialysis dosing is recommended, but dose adjustments may be warranted if haemodialysis starts within 3 h of telavancin administration