OAR@UM Collection:

Access to antidiabetic treatment and patient self-monitoring

2023-02-27T08:30:14Z

Title: Access to antidiabetic treatment and patient self-monitoring Abstract: Patient self-monitoring of blood glucose (SMBG) levels contributes to patient empowerment and optimisation of management of diabetes. The aims of this study were to: 1) Investigate the perception of patients with type 1 diabetes mellitus (T1DM) regarding SMBG and identify problems encountered when carrying out BG monitoring, 2) Assess the perception of patients on innovative self-monitoring practices, namely continuous glucose monitoring (CGM), and 3) study diabetes treatment available on the local national health service (NHS) and protocols on appropriate use of medicines, compare antidiabetic medicines available on the local market and assess the burden for patients if antidiabetic medicines are not present on the NHS formulary. A questionnaire on SMBG in English and Maltese language developed and validated in a previous study by Cassar to be completed by semi-structured interview was updated with the inclusion of a section on CGM. After ethics approval, the questionnaire was disseminated to T1DM patients ≥18 years recruited by convenience sampling from 15 community pharmacies; 3 from each of the 5 statistical districts in Malta. The NHS formulary was accessed and antidiabetic medications together with protocols for use were noted. Antidiabetic medications present in the private sector were then compared to medications available on NHS and economic burden was calculated. Seventy patients were interviewed; 38 were female and 52 had a duration of T1DM >5 years. The most frequent problems encountered with daily SMBG were painful finger pricking (n=37) and high cost of buying extra test strips (n=33). Five patients currently use a CGM device and 30 patients are willing to use a CGM device in the future. Forty-seven patients stated that time was a barrier for SMBG. Antidiabetic medication available on the private sector but are not available on the NHS include insulin degludec, insulin glulisine, glimepiride and sitagliptin. Patients are not adhering to the recommended daily schedule for SMBG for various reasons including access to test strips and time limitations. T1DM patients are entitled to 4 test strips a day for free on the national health scheme. Improving awareness and access to CGM is warranted to overcome the problems identified with SMBG. Patients requiring medications which are not available on the NHS are met with a heavy financial burden particularly when it comes to insulins Description: M.PHARM.

Design and identification of steroid receptor co-activator modulators for the management of Neoplastic Disease

2020-07-19T05:18:27Z

Title: Design and identification of steroid receptor co-activator modulators for the management of Neoplastic Disease Abstract: The Steroid Receptor Co-activator (SRC) is overexpressed in several cancer types such as colon, breast, and brain cancer. Wang et al. hypothesised that the overstimulation of the SRC might be able to disrupt tumour homeostasis. This results in tumour stress and tumour cell mortality. MCB-613 is a cytotoxic small molecule stimulator that overstimulates the transcriptional activity of the whole SRC family proteins. The small agonist molecule MCB-613 was docked into the apo SRC ligand binding pocket (LBP) obtained from Protein Data Bank (PDB) crystallographic deposition 2SRC. Conformational analysis was performed. The molecule with the lowest ligand binding energy (LBE) (Kcal/mol) and highest ligand binding affinity (LBA) (pKd) was identified as the optimal conformer, and its critical interactions with the SRC were used in a dual approach of virtual screening (VS) and de novo ligand growth. The modelled seed fragments generated by the de novo approach were planted within the generated SRC_LBP map and fragment growth was performed which resulted in a cohort of structures. A consensus pharmacophore was modelled and used for analog identification using MCB-613 best conformer. A protomol was generated and structures were identified for virtual screening. De novo growth yielded a total of 638 molecules, 405 of which were Lipinski Rule compliant. The VS approach yielded a total of 25 hits. The molecules which were designed de novo have an affinity superior to that of the endogenous ligand implying that these molecules would displace the endogenous antagonist in vivo, and that they could potentially therefore exert the desired super agonist effect. The optimal hits obtained through VS are the highest affinity molecules with physicochemical parameters which most strongly adhere to the rule of 3 for lead like structures and which consequently leave most room for further optimisation. Description: M.PHARM.

Medicine information and patient discharge

2020-07-19T05:19:09Z

Title: Medicine information and patient discharge Abstract: Medicine reconciliation is vital to the discharge process and can be improved by evaluation, reducing errors and readmissions, saving resources and improving quality of life. The scope of the study was to analyse prescribing trends and changes during hospitalisation and to identify frequency of drug classes. Clinical pharmacist compliance with discharge Standard Operating Procedure (SOP) and patient knowledge on medication changes during hospitalisation were assessed to find gaps in the process, along with healthcare professionals’ perception on medication reconciliation. The 30 patients recruited were over 18 years of age, had a chronic disease, were currently taking two or more drugs, had no severe cognitive impairment, and were discharged back to their private residence. Medication forms were compiled from patient files. Medicine reconciliation for each patient was observed at discharge. A patient questionnaire was filled, and SOP compliance was assessed. A questionnaire aimed at healthcare experts about the medication reconciliation process at discharge was carried out. A Likert scale of 1-5, with 5 being the highest, was used for the questionnaires. The study was carried out at Karen Grech Rehabilitation Hospital (KGRH). Outcome measures included medicine use in elderly patients, knowledge about medication changes at discharge, and healthcarer perception of medicine reconciliation. Twenty nine patients were aware of medicine changes. The mean patient rating of effectiveness of reconciliation was 4.5. The experts (n = 7) rated the process feasibility as 4.3, effectiveness as 4.7, and were willing to spend 20 minutes on patient reconciliation. The most common class, regimen and route in use during hospitalisation were antihypertensives (13.4%), daily (41.6%) and orally (88.1%). Chi-square tests identified significant associations between drug class and changes in dosage regimen (p = 0.022), as well as with changes in dose (p = 0.009), route of administration (p = 0.010), starting (p < 0.001) and stopping (p = 0.012) medications. The mean number of medications taken per patient is not significantly affected by age group (p = 0.896) but is higher for females (two-tailed p = 0.026). In conclusion, patients and professionals are satisfied with medicine reconciliation. Emphasis must be made during reconciliation, especially on antihypertensive changes. Description: M.PHARM.

Design and identification of partial Peroxisome proliferator activated receptor gamma (PPARγ) agonists using the synthetic analog of Tetrahydrocannabinol (THC) ajulemic acid (AJA) scaffold as a lead molecule

2020-07-19T05:19:07Z

Title: Design and identification of partial Peroxisome proliferator activated receptor gamma (PPARγ) agonists using the synthetic analog of Tetrahydrocannabinol (THC) ajulemic acid (AJA) scaffold as a lead molecule Abstract: PPARγ is a druggable target for the management of diabetes and inflammatory disease. Total agonism of this receptor produced clinically significant adverse effects, resulting in the withdrawal of entire drug classes specifically the glitazones from the market. The main objective of the study were; to use the bioactive conformation of AJA as lead molecule to probe the PPAR LBP. To identify critical interactions responsible for affinity and stability at this locus, identify optimal structures and validate their utility through molecular dynamics simulation. PDB crystallographic depositions, 20M9 and 4XUM describing bound coordinates of PPARγ bound to AJA and indomethacin respectively were recruited. The small molecules were extracted, and their bioactive coordinates were superimposed to generate a consensus pharmacophore. This was submitted as a query to the ZincPharmer® database. The idealised PPARγ LBP was modelled. The hits from the VS exercise were filtered for Lipinski Rule compliance, docked and ranked in order of affinity. A de novo approach was carried out where seeds retaining the critical fragments were modelled computationally. This study yielded 2 lead like molecular cohorts with high affinity for the PPAR. A cohort of 44,276 and 8 high affinity Lipinski Rule compliant molecules with known synthetic pathways were identified and grouped according to pharmacophoric similarity from the VS and de novo approach respectively. The highest ranked structures (n=5) were proposed for molecular dynamics. The selected structures provide guidance to understanding of partial agonism, suggesting a rational approach to the design of molecules capable of activating the receptor at levels that avoid undesirable side effects. Description: M.PHARM.