Opportunities to Digitally Enable Falls Prevention in Older Adults.

Falls are a serious problem confronting older adults. Evidence demonstrates that multifactorial interventions that target multiple risk factors can reduce falls. However, resource and access constraints impact intervention uptake and sustainability.

Adaptation and Implementation of a Volunteer-Delivered, Telephone-Based, Social Support Program HOW-R-U? During the COVID-19 Pandemic: A Pragmatic Study.

Background And Objectives: Public health concerns surrounding social isolation and loneliness heightened during the coronavirus disease 2019 (COVID-19) pandemic, as infection prevention measures led to increased feelings of loneliness and depression. Our objective was to evaluate the implementation of the HOW-R-U? program, during the pandemic (March 2020-December 2021). HOW-R-U? is a weekly volunteer-delivered telephone program designed to facilitate social connection and ease feelings of social isolation, loneliness, and depression in older people.

Development and application of a PBPK modeling strategy to support antimalarial drug development.

As part of a collaboration between Medicines for Malaria Venture (MMV), Certara UK and Monash University, physiologically-based pharmacokinetic (PBPK) models were developed for 20 antimalarials, using data obtained from standardized in vitro assays and clinical studies within the literature. The models have been applied within antimalarial drug development at MMV for more than 5 years. During this time, a strategy for their impactful use has evolved.

Risk Negotiation With People With Dementia: From Co-designed Paper Version to Implementation Preparation of an Electronic Conversation Tool.

The home care workforce provides essential support for older people with dementia to live a life of fulfillment. "," an evidence-informed conversation tool, aims to negotiate risk around everyday activities between home care workers, people with dementia and their informal carers. This paper describes tool conversion into electronic format and preparation for implementation throughout a large Australian health and aged care service provider, utilizing the Implementation Framework for Aged Care (IFAC).

Cycling Without Age: An Australian residential aged care home experience.

Objective: Cycling Without Age (CWA) involves taking residents on outdoor trishaw (electric bicycle) rides driven by trained 'pilots'. This study explored the CWA experience from the perspective of residents and family members, staff and volunteer pilots from a residential aged care home in Queensland, Australia.

Methods: A qualitative descriptive design was used.

An in vitro toolbox to accelerate anti-malarial drug discovery and development.

Background: Modelling and simulation are being increasingly utilized to support the discovery and development of new anti-malarial drugs. These approaches require reliable in vitro data for physicochemical properties, permeability, binding, intrinsic clearance and cytochrome P450 inhibition. This work was conducted to generate an in vitro data toolbox using standardized methods for a set of 45 anti-malarial drugs and to assess changes in physicochemical properties in relation to changing target product and candidate profiles.

Community-Dwelling Older Women: The Association Between Living Alone and Use of a Home Nursing Service.

Objective: To investigate the use of home nursing by community-dwelling older women to determine the nature of services required by those living alone.

Design: A retrospective cohort study using routinely collected data.

Setting And Participants: Women aged 55 years and older living in metropolitan Melbourne who received an episode of nursing care from a large community home-based nursing service provider between January 1, 2006 and December 31, 2015.

Co-creation of services to maintain independence and optimise well-being: Learnings from Australia's Older Women Living Alone (OWLA) project.

For many populations at risk of social isolation, including Older Women Living Alone (OWLA), existing services to maintain independence and optimise well-being are difficult to access, unsuitable or unavailable. Co-creation is a strategy to develop 'person-centred' services that meet the needs of individuals. We adapted an existing framework for co-creation and used participatory action research methods, supported by an evidence base comprising a systematic review, analysis of routinely collected data and interviews, to develop person-centred services for OWLA.

Trajectories of home nursing use for older women in Melbourne, Australia: 2006-2015.

Objective: To profile changes in older women accessing home nursing between 2006 and 2015, focussing on living circumstances.

Methods: Data pertaining to Australian women aged 55+ who accessed a home nursing service between 2006 and 2015 were analysed, stratified by living status. Comparisons were made between the years 2006 and 2015; rates and relative rates of use per 1000 clients were calculated.

Using co-creation and multi-criteria decision analysis to close service gaps for underserved populations.

Background: Navigating treatment pathways remains a challenge for populations with complex needs due to bottlenecks, service gaps and access barriers. The application of novel methods may be required to identify and remedy such problems.

Objective: To demonstrate a novel approach to identifying persistent service gaps, generating potential solutions and prioritizing action.

Profile of home nursing clients with mental health diagnoses: Epidemiological analysis of Australian community home nursing data.

Mental health is an important part of overall health status and mental ill health is common within the community. There is, however, little information relating to the mental health status of those in the community accessing services such as home nursing. The aim of this study is to profile mental health diagnoses and service use of persons accessing a community home nursing service.

Understanding the conceptualisation of risk in the context of community dementia care.

Risk has become a ubiquitous presence in modern society. For individuals diagnosed with dementia this preoccupation with risk can affect their day-to-day life in many ways. Maintaining autonomy while balancing risks is a continual struggle not only for those living with the disease, but also their carers, family and health professionals.

Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach.

Current formulations of combined oral contraceptives (COC) containing ethinylestradiol (EE) have ≤35 μg due to increased risks of cardiovascular diseases (CVD) with higher doses of EE. Low-dose formulations however, have resulted in increased incidences of breakthrough bleeding and contraceptive failure, particularly when coadministered with inducers of cytochrome P450 enzymes (CYP). The developed physiologically based pharmacokinetic model quantitatively predicted the effect of CYP3A4 inhibition and induction on the pharmacokinetics of EE.

Development of a discussion tool to enable well-being by providing choices for people with dementia: a qualitative study incorporating codesign and participatory action research.

Objective: To codesign a discussion tool to facilitate negotiation of risk between health professionals, people with dementia and carers.

Methods: A qualitative approach using codesign. Thematic analysis was used to analyse interviews and focus groups with people with dementia, carers, healthcare staff and healthy older people exploring the issue of risk in dementia, the acceptability and development of a discussion tool.

Change Strategies and Associated Implementation Challenges: An Analysis of Online Counselling Sessions.

Self-change is the most frequent way people limit or reduce gambling involvement and often the first choice of people experiencing gambling-related problems. Less well known is the range of change strategies gamblers use and how these are selected, initiated or maintained. This study examined change strategies discussed in counselling transcripts from 149 clients who accessed a national online gambling help service in Australia.

Social inclusion and the Fatosphere: the role of an online weblogging community in fostering social inclusion.

Overweight and obesity are one of the most salient issues within society today, and the stigmatisation of overweight individuals is prevalent and widespread. Utilising interviews with 44 individuals who blog within an online fat acceptance community known as the Fatosphere, participants' perceptions of inclusion and exclusion were examined within their offline and online environments. Additionally, the effect this had on their offline lives was examined.

The health and service needs of older veterans: a qualitative analysis.

Background: With substantial numbers of older people within the Australian veteran population continuing to age well within the community, appropriate planning of community support and health services is important for this ageing population.

Objective: The purpose of this research study was to investigate the health and service usage of a group of older Australian war veterans who receive Australian Government support for their health-care needs and conditions.

Design: This paper reports on qualitative data gathered from the longitudinal MELSHA study.

Translating research findings into community based theatre: More than a dead man's wife.

Increasingly, qualitative scholars in health and social sciences are turning to innovative strategies as a way of translating research findings into informative, accessible and enjoyable forms for the community. The aim of this article is to describe how the research findings of a doctoral thesis - a narrative study about 58 older women's experiences of widowhood - were translated into a unique and professionally developed script to form the basis for a successful theatrical production that has travelled extensively within Australia. This article reports on the process of collaboration between a researcher, a highly regarded Australian actor/script writer and an ensemble of well-known and experienced professional actors.

The evolution of the OATP hepatic uptake transport protein family in DMPK sciences: from obscure liver transporters to key determinants of hepatobiliary clearance.

Over the last two decades the impact on drug pharmacokinetics of the organic anion transporting polypeptides (OATPs: OATP-1B1, 1B3 and 2B1), expressed on the sinusoidal membrane of the hepatocyte, has been increasingly recognized. OATP-mediated uptake into the hepatocyte coupled with subsequent excretion into bile via efflux proteins, such as MRP2, is often referred to as hepatobiliary excretion. OATP transporter proteins can impact some drugs in several ways including pharmacokinetic variability, pharmacodynamic response and drug-drug interactions (DDIs).

Application of PBPK modelling in drug discovery and development at Pfizer.

Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties.

Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms.

PF-184298 ((S)-2,3-dichloro-N-isobutyl-N-pyrrolidin-3-ylbenzamide) and PF-4776548 ((3-(4-fluoro-2-methoxy-benzyl)-7-hydroxy-8,9-dihydro-3H,7H-pyrrolo[2,3-c][1,7]naphthyridin-6-one)) are novel compounds which were selected to progress to human studies. Discordant human pharmacokinetic predictions arose from pre-clinical in vivo studies in rat and dog, and from human in vitro studies, resulting in a clearance prediction range of 3 to >20 mL min⁻¹ kg⁻¹ for PF-184298, and 5 to >20 mL min⁻¹ kg⁻¹ for PF-4776548. A package of work to investigate the discordance for PF-184298 is described.

Effects of the moderate CYP3A4 inhibitor, fluconazole, on the pharmacokinetics of fesoterodine in healthy subjects.

What Is Already Known About This Subject: Available data suggest that fesoterodine dosage should not exceed 4 mg once daily when taken concomitantly with potent CYP3A4 inhibitors, such as ketoconazole. Currently, no information is available on whether dose adjustment is necessary when fesoterodine is administered with a moderate CYP3A4 inhibitor.

What This Study Adds: This study shows that adjustment of fesoterodine dose is not warranted when co-administered with a moderate CYP3A4 inhibitor.

Simulation of human intravenous and oral pharmacokinetics of 21 diverse compounds using physiologically based pharmacokinetic modelling.

Background: The importance of predicting human pharmacokinetics during compound selection has been recognized in the pharmaceutical industry. To this end there are many different approaches that are applied.

Methods: In this study we compared the accuracy of physiologically based pharmacokinetic (PBPK) methodologies implemented in GastroPlus™ with the one-compartment approach routinely used at Pfizer for human pharmacokinetic plasma concentration-time profile prediction.

An evaluation of ondansetron binding interactions with human cytochrome P450 enzymes CYP3A4 and CYP2D6.

The results of an evaluation study of ondansetron binding to human cytochromes P450 CYP3A4 and CYP2D6 is reported. The methodology includes NMR spectroscopic measurements of substrate to heme iron distances together with molecular modelling of the enzyme-substrate interactions. It is shown that there is a generally good agreement between the experimental and calculated binding affinities for ondansetron towards CYP2D6 and CYP3A4 enzymes, based on interactive docking studies.