Prescribing and deprescribing in older people with life-limiting illnesses receiving hospice care at the end of life: A longitudinal, retrospective cohort study.

BACKGROUND: Although prescribing and deprescribing practices in older people have been the subject of much research generally, there are limited data in older people at the end of life. This highlights the need for research to determine prescribing and deprescribing patterns, as a first step to facilitate guideline development for medicines optimisation in this vulnerable population. AIMS: To examine prescribing and deprescribing patterns in older people at the end of life and to determine the prevalence of potentially inappropriate medication use. DESIGN: A longitudinal, retrospective cohort study where medical records of eligible participants were reviewed, and data extracted. Medication appropriateness was assessed using two sets of consensus-based criteria; the STOPPFrail criteria and criteria developed by Morin et al. SETTING/PARTICIPANTS: Decedents aged 65 years and older admitted continuously for at least 14 days before death to three inpatient hospice units across Northern Ireland, who died between 1st January and 31st December 2018, and who had a known diagnosis, known cause of death and prescription data. Unexpected/sudden deaths were excluded. RESULTS: Polypharmacy was reported to be continued until death in 96.2% of 106 decedents (mean age of 75.6 years). Most patients received at least one potentially inappropriate medication at the end of life according to the STOPPFrail and the criteria developed by Morin et al. (57.5 and 69.8% respectively). Limited prevalence of proactive deprescribing interventions was observed. CONCLUSIONS: In the absence of systematic rationalisation of drug treatments, a substantial proportion of older patients continued to receive potentially inappropriate medication until death.

Healthcare professionals' perspectives of deprescribing in older patients at the end of life in hospice care: a qualitative study using the Theoretical Domains Framework.

OBJECTIVES: This study aimed to investigate healthcare professionals' barriers to and enablers of deprescribing in older hospice patients at the end of life and prioritise relevant theoretical domains for behaviour change to be incorporated into future interventions to facilitate deprescribing. METHODS: Twenty doctors, nurses and pharmacists from four hospices in Northern Ireland participated in qualitative semistructured interviews using Theoretical Domains Framework (TDF)-based topic guides. Data were recorded, transcribed verbatim and analysed inductively using thematic analysis. Deprescribing determinants were mapped to the TDF enabling the prioritisation of domains for behaviour change. KEY FINDINGS: Four prioritised TDF domains represented key barriers to deprescribing implementation; lack of formal documentation of deprescribing outcomes (Behavioural regulation), challenges in communication with patients and families (Skills), lack of implementation of deprescribing tools in practice (Environmental context/resources) and patient and caregiver perceptions of medication (Social influences). Access to information was identified as a key enabler (Environmental context/resources). Perceived risks versus benefits of deprescribing were identified as a key barrier or enabler (Beliefs about consequences). CONCLUSIONS: This study highlights that further guidance on deprescribing in the context of end-of-life is required to address the growing problems of inappropriate prescribing, Guidance should consider factors such as the adoption of deprescribing tools, monitoring and documentation of deprescribing outcomes and how best to discuss prognostic uncertainty.

Ligand-based computer aided drug design reveals new tropomycin receptor kinase a (TrkA) inhibitors.

Targeting tropomycin kinase A (TrkA) by small molecule inhibitors is considered as a promising strategy for treating several human cancers. To achieve this goal, a ligand based QSAR model was applied using the Discovery studio 4.5 (DS 4.5). Hence, a total list of 161 TrkA inhibitors was investigated. The TrkA inhibitors were extensively explored to detect their optimal physicochemical properties and pharmacophoric binding modes, which were converted into numeric descriptors and allowed to compete within the context of the Genetic Function Algorithm (GFA) approximations to find the subset of terms that correlates best with the activity. The resulted successful QSAR equation had statistical criteria of (r2129=0.67, r2LOO=0.61 r2PRESS against 32 external test inhibitors=0.50). Afterwards, the most successful pharmacophore: HypoB-T5-3, was used to screen compounds within the National Cancer institute (NCI) database. Only 41 compounds were retrieved and 21 of them exhibited anti-TrkA activity. The most potent hit had an IC50 value of 2.4µM. Later, upon docking the active hits into the TrkA binding pocket, important interactions were revealed including hydrogen bonding with the amino acids Asp668 and Lys544 in addition to the cation-π interactions with the sidechain of Arg559.