Multidisciplinary DEprescribing review for Frail oldER adults in long-term care (DEFERAL): Implementation strategy design using behaviour science tools and stakeholder engagement.

Introduction: Deprescribing is a strategy for reducing the use of potentially inappropriate medications for older adults. Limited evidence exists on the development of strategies to support healthcare professionals (HCPs) deprescribing for frail older adults in long-term care (LTC).

Objective: To design an implementation strategy, informed by theory, behavioural science and consensus from HCPs, which facilitates deprescribing in LTC.

Barriers and enablers to deprescribing in long-term care: A qualitative investigation into the opinions of healthcare professionals in Ireland.

Introduction: The prevalence of polypharmacy increases with age, increasing the exposure of older adults to potentially inappropriate medications (PIMs). Deprescribing has been shown to reduce PIMs for older residents in long-term care; however, deprescribing is not universally implemented. This study aims to identify the barriers and enablers to deprescribing in Irish long-term care facilities from the healthcare professionals' (HCPs) perspective.

Identification of Potentially Inappropriate Medications in Frail Older Adults Residing in Long-Term Care: A Retrospective Chart Review Study.

Introduction: Deprescribing is associated with positive health outcomes for older adults in long-term care (LTC), however deprescribing is not universally implemented.

Objective: The primary aim of this study was to estimate the prevalence of potentially inappropriate medications (PIMs) prescribed to frail older adults in Irish long-term care facilities (LTCFs), as identified by the Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy, version 2 (STOPPFrail v2).

Methods: A retrospective chart review was conducted in two publicly funded LTCFs in Ireland.

Barriers and enablers to deprescribing in long-term care facilities: a 'best-fit' framework synthesis of the qualitative evidence.

Introduction: older adults are at risk of adverse outcomes due to a high prevalence of polypharmacy and potentially inappropriate medications (PIMs). Deprescribing interventions have been demonstrated to reduce polypharmacy and PIMs. However, deprescribing is not performed routinely in long-term care facilities (LTCFs).

Assessing community pharmacists' attitudes towards identifying opportunities for deprescribing in clinical practice in Ireland.

Objectives: The main objective of this study was to assess community pharmacists' thoughts regarding the role they can play in effectively integrating deprescribing into clinical practice in Ireland. The aim was to assess pharmacists' (1) knowledge of deprescribing, (2) confidence in deprescribing, (3) attitudes towards deprescribing and (4) barriers and facilitators to deprescribing in a community pharmacy setting.

Methods: An online questionnaire was disseminated to pharmacists currently registered with the Pharmaceutical Society of Ireland, with instruction only to complete if working in community pharmacy.

The Prevalence of and Documented Indications for Antipsychotic Prescribing in Irish Nursing Homes.

Background: Antipsychotic medications are often used 'off-licence' to treat neuropsychiatric symptoms and disorders of aging and to manage behavioural and psychological symptoms of dementia despite the warnings of adverse effects.

Objective: To establish the prevalence of and documented indication for antipsychotic medication use in the Irish nursing home setting.

Setting: This study was conducted in six nursing homes located in Co.

Perspectives of pharmacists on facilitating experiential learning placements for pharmacy students in non-patient facing settings.

Introduction: Recently, the model of pharmacy education in Ireland changed to a five-year pharmacy degree, with three distinct blocks of experimental placements dispersed throughout the degree. The United Kingdom is also considering the introduction of a similar five-year pharmacy degree, while the United States is looking to further expand non-clinical experiential learning opportunities. This study was carried out to ascertain the perspectives of pharmacists working in non-patient facing roles on the barriers to and facilitators of placements to aid in identifying placement recruitment strategies for non-patient facing placements.

Application of a physiologically-based pharmacokinetic model for the prediction of bumetanide plasma and brain concentrations in the neonate.

Bumetanide is a loop diuretic that is proposed to possess a beneficial effect on disorders of the central nervous system, including neonatal seizures. Therefore, prediction of unbound bumetanide concentrations in the brain is relevant from a pharmacological prospective. A physiologically-based pharmacokinetic (PBPK) model was developed for the prediction of bumetanide disposition in plasma and brain in adult and paediatric populations.

Pharmacokinetic, pharmacodynamic and biodistribution following oral administration of nanocarriers containing peptide and protein drugs.

The influence of nanoparticle (NP) formulations on the pharmacokinetic, pharmacodynamic and biodistribution profiles of peptide- and protein-like drugs following oral administration is critically reviewed. The possible mechanisms of absorption enhancement and the effects of the physicochemical properties of the NP are examined. The potential advantages and challenges of physiologically-based pharmacokinetic (PBPK) modelling to help predict efficacy in man are discussed.

Pharmacotherapy for Neonatal Seizures: Current Knowledge and Future Perspectives.

Seizures are the most common neurological emergencies in the neonatal period and are associated with poor neurodevelopmental outcomes. Seizures affect up to five per 1000 term births and population-based studies suggest that they occur even more frequently in premature infants. Seizures are a sign of an underlying cerebral pathology, the most common of which is hypoxic-ischaemic encephalopathy in term infants.

In vitro bidirectional permeability studies identify pharmacokinetic limitations of NKCC1 inhibitor bumetanide.

Recently, it has been suggested that bumetanide, an inhibitor of the Na-K-2Cl co-transporter (NKCC1), may be useful in the treatment of central nervous system (CNS) disorders. However, from a physicochemical perspective, bumetanide may not cross the blood-brain barrier to the extent that is necessary for it to be an effective brain NKCC1 inhibitor in vivo. High plasma-protein binding, potentially high brain-tissue binding and putative efflux transporters including organic anion transporter 3 (OAT3) contribute to the poor pharmacokinetic profile of bumetanide.

Treating disorders of the neonatal central nervous system: pharmacokinetic and pharmacodynamic considerations with a focus on antiepileptics.

A major consideration in the treatment of neonatal disorders is that the selected drug, dose and dosage frequency is safe, effective and appropriate for the intended patient population. Thus, a thorough knowledge of the pharmacokinetics and pharmacodynamics of the chosen drug within the patient population is essential. In paediatric and neonatal populations two additional challenges can often complicate drug treatment - the inherently greater physiological variability, and a lack of robust clinical evidence of therapeutic range.

The effect of organic anion transporter 3 inhibitor probenecid on bumetanide levels in the brain: an integrated in vivo microdialysis study in the rat.

Objectives: Recent data highlight the potential of bumetanide as a treatment for neonatal seizures and autism, as it facilitates the excitatory to inhibitory switch in gamma-aminobutyric acid signalling. This study examines the extent of blood-brain barrier (BBB) permeation of bumetanide, a key determinant of the efficacy of centrally acting drugs. Furthermore, the impact of efflux transporter organic anion transporter 3 (oat3) inhibition on bumetanide pharmacokinetics was investigated.

The P-glycoprotein inhibitor cyclosporin A differentially influences behavioural and neurochemical responses to the antidepressant escitalopram.

Recent studies have raised the possibility that P-glycoprotein (P-gp) inhibition may represent a putative augmentation strategy for treatment with certain antidepressants. Indeed, we have previously shown that administration of the P-gp inhibitor verapamil increased the brain distribution and behavioural effects of the antidepressant escitalopram. The aim of the current study was to investigate if similar effects occur with another P-gp inhibitor, cyclosporin A (CsA).