Pharmacist-led interventions during transitions of care of older adults admitted to short term geriatric units: Current practices and perceived barriers.

Background: During transitions of care, older adults are at risk of adverse drug events which could lead to avoidable hospital visits. Pharmacists are increasingly involved in care teams at various stages of the continuum of care. The types and frequency of clinical interventions performed by pharmacists in the geriatric practice setting remain poorly documented. Objectives: This study aimed to describe the current integration of pharmacist interventions during transitions of care of older adults admitted in short-term geriatric units (STGUs) and to explore barriers and facilitators to their implementation in clinical practice. The secondary objective was to explore associations between certain patient characteristics and pharmacist-led interventions during transitional care. Methods: A mixed methods study was conducted with pharmacists practicing in STGUs in the Montreal area, Canada. The application of 8 pharmaceutical interventions was assessed using a self-administered questionnaire, along with as a retrospective chart review. Four semi-structured group interviews were conducted in order to identify perceived barriers and facilitators. Results: Thirteen pharmacists participated in the study. In the questionnaire, medication reconciliation on admission and at discharge was reported as being performed at least half the time by 12 (92%) and 7 (54%) pharmacists, respectively. The retrospective chart review revealed that these interventions were documented in 95 (98%) and 25 (26%) files, respectively. While 35% of patients had a documented pharmaceutical care plan on admission, none was documented at discharge. Several barriers to implementing clinical interventions were identified such as lack of time, technical support, communication and standardization. Conclusions: Pharmacists are involved at different periods of transitional care; however, certain barriers should be addressed in order to expand their role in discharge planning. Providing guidelines on what is expected at discharge and post-discharge, and having a practice focused on delegation and collaboration would help pharmacists increase their role throughout the transition of care of older adults.

Ceftazidime-Induced Neurotoxicity in an 80-Year-Old Female With Renal Dysfunction: A Case Report.

Neurological toxicity is a relatively rare adverse reaction reported in elderly patients treated with cephalosporins. We present a case of ceftazidime-induced encephalopathy in the context of acute kidney injury in an 80-year-old female treated for a Pseudomonas aeruginosa prosthetic joint infection. During the course of treatment, the patient developed sudden confusion and disorientation. The patient's mental state progressively worsened, eventually leading to intubation and admission to the intensive care unit. As imaging and laboratory analyses revealed no alternative causes explaining the patient's symptoms, ceftazidime was stopped under the suspicion of drug-induced neurotoxicity. Shortly after ceftazidime discontinuation, the patient's condition drastically improved and returned to baseline within 5 days. This case reveals the potential severity of cephalosporin-induced neurotoxicity in elderly patients and highlights the importance of quickly detecting such adverse events in order to prevent dire outcomes.

Impact of pharmacist interventions during transition of care in older adults to reduce the use of healthcare services: A scoping review.

BACKGROUND: Current literature has shown increasing risk of error in transition of care between different healthcare settings, especially in the older population. Moreover, drug-related hospital readmission has been reported due to lack of appropriate communication. However, the literature is not clear about the impact of pharmacist interventions during transition of care of older adults on the reduction in use of healthcare services. OBJECTIVE: The goal of the scoping review was to describe the impact of pharmacist interventions during transitions of care for older adults on the use of healthcare services. METHODS: MEDLINE was searched for randomized controlled trials and controlled studies that analyzed pharmacist interventions during transition of care of older adults with regard to use of healthcare services. Four reviewers, grouped in pairs, independently screened all references published from 1990 to 2019 and extracted and analyzed the data. A pharmaceutical model of 8 pharmacist-led interventions was adapted from literature to compare the included studies. RESULTS: There were 1527 publications screened, 17 of which met inclusion criteria. Pharmacist-led interventions decreased the use of healthcare services in 11 of these studies. The majority of studies were of very good or good quality based on Mixed Methods Appraisal Tool. Pharmacist were implicated at all times during the transition of care process (i.e. admission/during stay, discharge and post-discharge) in 4 of the effective studies, whereas none did in the not effective studies. More interventions were accomplished by pharmacists in studies with positive outcomes. CONCLUSION: By diversifying their interventions at different moments throughout transition of care, pharmacists can reduce the use of healthcare services for older adults during transition of care. This scoping review also shows the need to better understand key components of post-discharge interventions and to have a dynamic pharmaceutical model accepted by the scientific community.

Effect of O6-Substituted Guanine Analogs on O6-methylguanine DNA-methyltransferase Expression and Glioblastoma Cells Viability.

BACKGROUND: Glioblastoma multiforme (GBM) is often associated with a poor survival prognostic for patients. The main reason seems to be the acquired or inherent resistance to the chemotherapeutic agent used to treat the tumor, temozolomide (TMZ). To this day, the most recognized pathway of resistance is the DNA Direct Repair pathway by the means of the protein O6- methylguanine DNA-methyltransferase (MGMT). OBJECTIVES: To design and synthesize a series of MGMT inhibitors that can sensitize GBM cells to TMZ. METHODS: Twenty-five O6-alkyl, O6-aryl and O6-substituted-aryl guanine analogs including nine novel compounds were synthesized, characterized, analyzed by molecular docking and tested on the T98G GBM cells viability. RESULTS: Following molecular modeling with MGMT, the newly designed compounds 19, 22, and 24 emerged as the most promising MGMT ligands and displayed modest cytotoxicity. Guanine analog (19), bearing a p-nitrobenzyl moiety, reduced considerably the O6-methylguanine DNAmethyltransferase expression level. When combined with TMZ (1), which is used as first line treatment for brain tumors, compounds 19, 22, and 24 decreased T98G cells proliferation by 32%, 68% and 50%, respectively. TMZ (1) displayed negligible effect on the proliferation of these cells further supporting the notion that this cell model is resistant to this alkylating agent. CONCLUSION: Overall, these results notably highlight a group of MGMT inhibitors that warrants further exploration in the development of therapeutic options to circumvent TMZ resistance in brain tumors.

Exploring miRNA-Associated Signatures with Diagnostic Relevance in Glioblastoma Multiforme and Breast Cancer Patients.

The growing attention that non-coding RNAs have attracted in the field of cancer research in recent years is undeniable. Whether investigated as prospective therapeutic targets or prognostic indicators or diagnostic biomarkers, the clinical relevance of these molecules is starting to emerge. In addition, identification of non-coding RNAs in a plethora of body fluids has further positioned these molecules as attractive non-invasive biomarkers. This review will first provide an overview of the synthetic cascade that leads to the production of the small non-coding RNAs microRNAs (miRNAs) and presents their strengths as biomarkers of disease. Our interest will next be directed at exploring the diagnostic utility of miRNAs in two types of cancer: the brain tumor glioblastoma multiforme (GBM) and breast cancer. Finally, we will discuss additional clinical implications associated with miRNA detection as well as introduce other non-coding RNAs that have generated recent interest in the cancer research community.