Co-Designing a Consult Patient Decision Aid for Continuation Versus Deprescribing Cholinesterase Inhibitors in People Living with Dementia.

BACKGROUND AND OBJECTIVE: As dementia progresses, people living with dementia may take high-risk, unnecessary, or ineffective medicines. Cholinesterase inhibitors (ChEIs) may have benefit in some people with dementia; however, up to one third are continued when no longer necessary or safe. Our aim was to co-design a consult patient decision aid (CPtDA) to support shared decision making between healthcare professionals and consumers about continuing or deprescribing ChEIs. METHODS: A systematic process was employed to design and test the CPtDA prototype. First, a steering group composed of healthcare professionals and a consumer representative was assembled. Guided by the International Patient Decision Aids Standards, the steering group defined the CPtDA's purpose, scope, and target audience and drafted the prototype for further testing. Interviews with consumers and healthcare professionals were conducted to gain feedback on the content, format, structure, comprehensibility and usability of the CPtDA prototype. RESULTS: After the steering group developed the CPtDA prototype, interviews were conducted with 11 consumers and six healthcare professionals. The content and format of the decision aid were improved iteratively over three rounds after consolidating the feedback at each round. The main changes included rewording the purpose of the decision aid and simplifying its layout and format. Participants reported that the decision aid is comprehensible and may be useful in practice. CONCLUSIONS: Limited available resources guide shared decision making about deprescribing. This study resulted in a co-designed and alpha-tested CPtDA for people living with dementia and carers to help them review the ongoing need for their ChEIs. Further research is needed to explore using the CPtDA in practice to support people living with dementia and their carers engage in the shared decision-making process about continuing or deprescribing their ChEIs. Our co-designed CPtDA could help people living with dementia and their carers review their goals of care alongside their healthcare professional. This may prompt conversations about appropriately using ChEIs and increase the uptake of deprescribing.

Neurophysiological patterns reflecting vulnerability to delirium subtypes: a resting-state EEG and event-related potential study.

Delirium is a common and acute neurocognitive disorder in older adults associated with increased risk of dementia and death. Understanding the interaction between brain vulnerability and acute stressors is key to delirium pathophysiology, but the neurophysiology of delirium vulnerability is not well defined. This study aimed to identify pre-operative resting-state EEG and event-related potential markers of incident delirium and its subtypes in older adults undergoing elective cardiac procedures. This prospective observational study included 58 older participants (mean age = 75.6 years, SD = 7.1; 46 male/12 female); COVID-19 restrictions limited recruitment. Baseline assessments were conducted in the weeks before elective cardiac procedures and included a 4-min resting-state EEG recording (2-min eyes open and 2-min eyes closed), a 5-min frequency auditory oddball paradigm recording, and cognitive and depression examinations. Periodic peak power, peak frequency and bandwidth measures, and aperiodic offsets and exponents were derived from resting-state EEG data. Event-related potentials were measured as mean component amplitudes (first positive component, first negative component, early third positive component, and mismatch negativity) following standard and deviant auditory stimuli. Incident delirium occurred in 21 participants: 10 hypoactive, 6 mixed, and 5 hyperactive. Incident hyperactive delirium was associated with higher pre-operative eyes open (P = 0.045, d = 1.0) and closed (P = 0.036, d = 1.0) aperiodic offsets. Incident mixed delirium was associated with significantly larger pre-operative first positive component amplitudes to deviants (P = 0.037, d = 1.0) and larger third positive component amplitudes to standards (P = 0.025, d = 1.0) and deviants (P = 0.041, d = 0.9). Other statistically non-significant but moderate-to-large effects were observed in relation to all subtypes. We report evidence of neurophysiological markers of delirium risk weeks prior to elective cardiac procedures in older adults. Despite being underpowered due to COVID-19-related recruitment impacts, these findings indicate pre-operative dysfunction in neural excitation/inhibition balance associated with different delirium subtypes and warrant further investigation on a larger scale.

Predictors of mortality shortly after entering a long-term care facility.

OBJECTIVE: Moving into a long-term care facility (LTCF) requires substantial personal, societal and financial investment. Identifying those at high risk of short-term mortality after LTCF entry can help with care planning and risk factor management. This study aimed to: (i) examine individual-, facility-, medication-, system- and healthcare-related predictors for 90-day mortality at entry into an LTCF and (ii) create risk profiles for this outcome. DESIGN: Retrospective cohort study using data from the Registry of Senior Australians. SUBJECTS: Individuals aged ≥ 65 years old with first-time permanent entry into an LTCF in three Australian states between 01 January 2013 and 31 December 2016. METHODS: A prediction model for 90-day mortality was developed using Cox regression with the purposeful variable selection approach. Individual-, medication-, system- and healthcare-related factors known at entry into an LTCF were examined as predictors. Harrell's C-index assessed the predictive ability of our risk models. RESULTS: 116,192 individuals who entered 1,967 facilities, of which 9.4% (N = 10,910) died within 90 days, were studied. We identified 51 predictors of mortality, five of which were effect modifiers. The strongest predictors included activities of daily living category (hazard ratio [HR] = 5.41, 95% confidence interval [CI] = 4.99-5.88 for high vs low), high level of complex health conditions (HR = 1.67, 95% CI = 1.58-1.77 for high vs low), several medication classes and male sex (HR = 1.59, 95% CI = 1.53-1.65). The model out-of-sample Harrell's C-index was 0.773. CONCLUSIONS: Our mortality prediction model, which includes several strongly associated factors, can moderately well identify individuals at high risk of mortality upon LTCF entry.

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial.

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45-60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45-60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke's Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective.

Ethnic differences in those presenting for outpatient management of venous leg ulcers.

AIM: To describe the demographics of those presenting to Capital & Coast DHB District Nursing Service with venous leg ulcers (VLU). METHODS: Electronic records were searched between January 2015 and December 2020 for those presenting with VLU and matched to the national minimum dataset to obtain ethnicity, age at presentation and gender. Numbers were standardised against the census data for the DHB population, to allow comparison of ethnic differences. Analysis was by prioritised ethnicity: comparing Pasifika, Maori and Other. RESULTS: Of 999 patients with VLU treated by the DN service, there were 91 Maori, 114 Pasifika, and 794 other ethnicities. Five hundred and fifty-nine were female and 440 were male. Pasifika men and women were greatly over-represented with relative risks of 20 and 19, respectively. Maori men and women had lower relative risk of 6.6 and 5.0, respectively. In addition, Maori and Pasifika presented earlier, with standardised rates greater than other ethnicities in all age groups up to the age of 70. Average age at presentation for Maori was 14-16, and Pasifika 17-18 years, younger than Other. CONCLUSION: This analysis shows for the first time that Maori and Pasifika have higher rates and present earlier than those of other ethnicities. Further investigation is required to understand the causes of earlier presentation and thereby prevent VLU.

DelIrium VULnerability in GEriatrics (DIVULGE) study: a protocol for a prospective observational study of electroencephalogram associations with incident postoperative delirium.

INTRODUCTION: Delirium is a neurocognitive disorder common in older adults in acute care settings. Those who develop delirium are at an increased risk of dementia, cognitive decline and death. Electroencephalography (EEG) during delirium in older adults is characterised by slowing and reduced functional connectivity, but markers of vulnerability are poorly described. We aim to identify EEG spectral power and event-related potential (ERP) markers of incident delirium in older adults to understand neural mechanisms of delirium vulnerability. Characterising delirium vulnerability will provide substantial theoretical advances and outcomes have the potential to be translated into delirium risk assessment tools. METHODS AND ANALYSIS: We will record EEG in 90 participants over 65 years of age prior to elective coronary artery bypass grafting (CABG) or transcatheter aortic valve implantation (TAVI). We will record 4-minutes of resting state (eyes open and eyes closed) and a 5-minute frequency auditory oddball paradigm. Outcome measures will include frequency band power, 1/f offset and slope, and ERP amplitude measures. Participants will undergo cognitive and EEG testing before their elective procedures and daily postoperative delirium assessments. Group allocation will be done retrospectively by linking preoperative EEG data according to postoperative delirium status (presence, severity, duration and subtype). ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of the Royal Adelaide Hospital, Central Adelaide Local Health Network and the University of South Australia Human Ethics Committee. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001114235 and ACTRN12618000799257.

Predictors of hospitalisations and emergency department presentations shortly after entering a residential aged care facility in Australia: a retrospective cohort study.

OBJECTIVES: To: (1) examine the 90-day incidence of unplanned hospitalisation and emergency department (ED) presentations after residential aged care facility (RACF) entry, (2) examine individual-related, facility-related, medication-related, system-related and healthcare-related predictors of these outcomes and (3) create individual risk profiles. DESIGN: Retrospective cohort study using the Registry of Senior Australians. Fine-Gray models estimated subdistribution HRs and 95% CIs. Harrell's C-index assessed risk models' predictive ability. SETTING AND PARTICIPANTS: Individuals aged ≥65 years old entering a RACF as permanent residents in three Australian states between 1 January 2013 and 31 December 2016 (N=116 192 individuals in 1967 RACFs). PREDICTORS EXAMINED: Individual-related, facility-related, medication-related, system and healthcare-related predictors ascertained at assessments or within 90 days, 6 months or 1 year prior to RACF entry. OUTCOME MEASURES: 90-day unplanned hospitalisation and ED presentation post-RACF entry. RESULTS: The cohort median age was 85 years old (IQR 80-89), 62% (N=71 861) were women, and 50.5% (N=58 714) had dementia. The 90-day incidence of unplanned hospitalisations was 18.0% (N=20 919) and 22.6% (N=26 242) had ED presentations. There were 34 predictors of unplanned hospitalisations and 34 predictors of ED presentations identified, 27 common to both outcomes and 7 were unique to each. The hospitalisation and ED presentation models out-of-sample Harrell's C-index was 0.664 (95% CI 0.657 to 0.672) and 0.655 (95% CI 0.648 to 0.662), respectively. Some common predictors of high risk of unplanned hospitalisation and ED presentations included: being a man, age, delirium history, higher activity of daily living, behavioural and complex care needs, as well as history, number and recency of healthcare use (including hospital, general practitioners attendances), experience of a high sedative load and several medications. CONCLUSIONS: Within 90 days of RACF entry, 18.0% of individuals had unplanned hospitalisations and 22.6% had ED presentations. Several predictors, including modifiable factors, were identified at the time of care entry. This is an actionable period for targeting individuals at risk of hospitalisations.

Identifying New Factors Associated With Cognitive Decline and Delirium After Transcatheter Aortic Valve Implantation: A Study Protocol.

Background: Transcatheter aortic valve implantation (TAVI) has become the standard-of-care for treatment of severe symptomatic aortic stenosis and is also being increasingly recommended for low-risk patients. While TAVI boasts positive post-procedural outcomes, it is also associated with cognitive complications, namely delirium and cognitive decline. There is a pressing need for accurate risk tools which can identify TAVI patients at risk of delirium and cognitive decline, as risk scores designed for general cardiovascular surgery fall short. The present effect-finding exploratory study will assess the utility of various measures in the context of aging and frailty in predicting who will and who will not develop delirium or cognitive impairment following TAVI. The measures we propose include gait, visual symptoms, voice, swallowing, mood and sleep. Methods: This is an observational prospective cohort study focused on identifying pre-procedural risk factors for the development of delirium and cognitive decline following TAVI. Potential risk factors will be measured prior to TAVI. Primary outcomes will be post-procedure cognitive decline and delirium. Secondary outcomes include activities of daily living, quality of life, and mortality. Delirium presence will be measured on each of the first 2 days following TAVI. All other outcomes will be assessed at 3-, 6-, and 12-months post-operatively. A series of logistic regressions will be run to investigate the relationship between potential predictors and outcomes (presence vs. absence of either delirium or cognitive decline). Discussion: This study will assess the strengths of associations between a range of measures drawn from frailty and aging literature in terms of association with cognitive decline and delirium following TAVI. Identified measures can be used in future development of TAVI risk prediction models, which are essential for the accurate identification of cognitive at-risk patients and successful application of pre-procedural interventions. Clinical Trial Registration: This trial is registered with the Australian New Zealand Clinical Trials Registry. [https://bit.ly/2PAotP5], [ACTRN12618001114235].

Predictors of short-term hospitalization and emergency department presentations in aged care.

OBJECTIVES: To examine individual, medication, system, and healthcare related predictors of hospitalization and emergency department (ED) presentation within 90 days of entering the aged care sector, and to create risk-profiles associated with these outcomes. DESIGN AND SETTING: Retrospective population-based cohort study using data from the Registry of Senior Australians. PARTICIPANTS: Older people (aged 65 and older) with an aged care eligibility assessment in South Australia between January 1, 2013 and May 31, 2016 (N = 22,130). MEASUREMENTS: Primary outcomes were unplanned hospitalization and ED presentation within 90 days of assessment. Individual, medication, system, and healthcare related predictors of the outcomes at the time of assessment, within 90 days or 1-year prior. Fine-Gray models were used to calculate subdistribution hazard ratios (sHR) and 95% confidence intervals (CI). Harrell's C-index assessed predictive ability. RESULTS: Four thousand nine-hundred and six (22.2%) individuals were hospitalized and 5028 (22.7%) had an ED presentation within 90 days. Predictors of hospitalization included: being a man (hospitalization sHR = 1.33, 95% CI 1.26-1.42), ≥3 urgent after-hours attendances (hospitalization sHR = 1.21, 95% CI 1.06-1.39), increasing frailty index score (hospitalization sHR = 1.19, 95% CI 1.11-1.28), individuals using glucocorticoids (hospitalization sHR = 1.11, 95% CI 1.02-1.20), sulfonamides (hospitalization sHR = 1.18, 95% CI 1.10-1.27), trimethoprim antibiotics (hospitalization sHR = 1.15, 95% CI 1.03-1.29), unplanned hospitalizations 30 days prior (hospitalization sHR = 1.13, 95% CI 1.04-1.23), and ED presentations 1 year prior (hospitalization sHR = 1.07, 95% CI 1.04-1.10). Similar predictors and hazard estimates were also observed for ED presentations. The hospitalization models out-of-sample predictive ability (C-index = 0.653, 95% CI 0.635-0.670) and ED presentations (C-index = 0.647, 95% CI 0.630-0.663) were moderate. CONCLUSIONS: One in five individuals with aged care eligibility assessments had unplanned hospitalizations and/or ED presentation within 90 days with several predictors identified at the time of aged care eligibility assessment. This is an actionable period for targeting at-risk individuals to reduce hospitalizations.

An integrated knowledge translation approach to address avoidable rehospitalisations and unplanned admissions for older people in South Australia: implementation and evaluation program plan.

BACKGROUND: Repeated admission to hospital can be stressful for older people and their families and puts additional pressure on the health care system. While there is some evidence about strategies to better integrate care, improve older patients' experiences at transitions of care, and reduce preventable hospital readmissions, implementing these strategies at scale is challenging. This program of research comprises multiple, complementary research activities with an overall goal of improving the care for older people after discharge from hospital. The program leverages existing large datasets and an established collaborative network of clinicians, consumers, academics, and aged care providers. METHODS: The program of research will take place in South Australia focusing on people aged 65 and over. Three inter-linked research activities will be the following: (1) analyse existing registry data to profile individuals at high risk of emergency department encounters and hospital admissions; (2) evaluate the cost-effectiveness of existing 'out-of-hospital' programs provided within the state; and (3) implement a state-wide quality improvement collaborative to tackle key interventions likely to improve older people's care at points of transitions. The research is underpinned by an integrated approach to knowledge translation, actively engaging a broad range of stakeholders to optimise the relevance and sustainability of the changes that are introduced. DISCUSSION: This project highlights the uniqueness and potential value of bringing together key stakeholders and using a multi-faceted approach (risk profiling; evaluation framework; implementation and evaluation) for improving health services. The program aims to develop a practical and scalable solution to a challenging health service problem for frail older people and service providers.

Relationships between the Bone Expression of Alzheimer's Disease-Related Genes, Bone Remodelling Genes and Cortical Bone Structure in Neck of Femur Fracture.

Neck of femur (NOF) fracture is a prevalent fracture type amongst the ageing and osteoporotic populations, commonly requiring total hip replacement (THR) surgery. Increased fracture risk has also been associated with Alzheimer's disease (AD) in the aged. Here, we sought to identify possible relationships between the pathologies of osteoporosis and dementia by analysing bone expression of neurotropic or dementia-related genes in patients undergoing THR surgery for NOF fracture. Femoral bone samples from 66 NOF patients were examined for expression of the neurotropic genes amyloid precursor protein (APP), APP-like protein-2 (APLP2), Beta-Secretase Cleaving Enzyme-1 (BACE1) and nerve growth factor (NGF). Relationships were examined between the expression of these and of bone regulatory genes, systemic factors and bone structural parameters ascertained from plain radiographs. We found strong relative levels of expression and positive correlations between APP, APLP2, BACE1 and NGF levels in NOF bone. Significant correlations were found between APP, APLP2, BACE1 mRNA levels and bone remodelling genes TRAP, RANKL, and the RANKL:OPG mRNA ratio, indicative of potential functional relationships at the time of fracture. Analysis of the whole cohort, as well as non-dementia (n = 53) and dementia (n = 13) subgroups, revealed structural relationships between APP and APLP2 mRNA expression and lateral femoral cortical thickness. These findings suggest that osteoporosis and AD may share common molecular pathways of disease progression, perhaps explaining the common risk factors associated with these diseases. The observation of a potential pathologic role for AD-related genes in bone may also provide alternative treatment strategies for osteoporosis and fracture prevention.

Investigating how electroencephalogram measures associate with delirium: A systematic review.

Delirium is a common neurocognitive disorder in hospital settings, characterised by fluctuating impairments in attention and arousal following an acute precipitant. Electroencephalography (EEG) is a useful method to understand delirium pathophysiology. We performed a systematic review to investigate associations between delirium and EEG measures recorded prior, during, and after delirium. A total of 1,655 articles were identified using PsycINFO, Embase and MEDLINE, 31 of which satisfied inclusion criteria. Methodological quality assessment was undertaken, resulting in a mean quality score of 4 out of a maximum of 5. Qualitative synthesis revealed EEG slowing and reduced functional connectivity discriminated between those with and without delirium (i.e. EEG during delirium); the opposite pattern was apparent in children, with cortical hyperexcitability. EEG appears to have utility in differentiating those with and without delirium, but delirium vulnerability and the long-term effects on brain function require further investigation. Findings provide empirical support for the theory that delirium is a disorder of reduced functional brain integration.

Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial.

INTRODUCTION: Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates; however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG. METHODS AND ANALYSIS: This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1-2 weeks of CCT preoperatively (45-60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45-60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence); the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research. TRIAL REGISTRATION NUMBER: This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257.