A Temporospatial Analysis of Activity Patterns for Fall Risk Assessment in Older Adults with Comorbid Type 2 Diabetes.

This study explores how daily activities, including duration and location within the home, affect fall risk in older adults with type 2 diabetes. Body-worn cameras on 26 participants provided data on activity (e.g. exercise), time and location (kitchen, living room). Demographics and health factors were considered to understand their influence. By visualising activity patterns, this study aimed to identify behaviours linked to falls to inform personalised fall prevention strategies and digital technologies for independent living.

Communication during telemedicine consultations in general practice: perspectives from general practitioners and their patients.

BACKGROUND: Telemedicine allows delivery of healthcare to occur between parties that are not in the same location. As telemedicine users are not co-present, effective communication methods are crucial to the delivery and reception of information. The aim of this study was to explore perspectives of general practitioners (GPs) and patients on the interactional components of telemedicine consultations. METHODS: Semi-structured qualitative interviews were held with telemedicine users; 15 GPs and nine patients self-selected from a larger telemedicine study. Participants were asked about their preparation for telemedicine consultations, conducting telemedicine consultations and post-consultation activities. Deidentified transcripts from the interviews were analysed thematically. RESULTS: GPs and patients discussed factors they used to decide whether a consultation would be best conducted by telemedicine or in-person; the condition to be discussed, the existing doctor-patient relationship and whether physical examination was required. Participants also described how they prepared for their telemedicine consultations, gathering relevant documents, and reading previous notes. Participants described strategies they employed to optimise the telemedicine interaction; improving conversational flow and building rapport, as well as difficulties they experienced when trying to provide and receive care via telemedicine. CONCLUSIONS: Patient factors including health literacy and familiarity with technology affect the transfer of information shared during telemedicine consultations and consideration of these factors when choosing patients for telemedicine is required. Many GPs and patients have innate communication skills to effectively deliver and receive care through telemedicine. However, they may not be aware of these subconscious techniques to use to optimise telemedicine consultations. Communication training could be delivered to increase conversational flow, build rapport, and establish safety netting.

ORF48 is required for optimal lytic replication of Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes persistent infection in the host by encoding a vast network of proteins that aid immune evasion. One of these targeted innate immunity pathways is the cGAS-STING pathway, which inhibits the reactivation of KSHV from latency. Previously, we identified multiple cGAS/STING inhibitors encoded by KSHV, suggesting that the counteractions of this pathway by viral proteins are critical for maintaining a successful KSHV life cycle. However, the detailed mechanisms of how these viral proteins block innate immunity and facilitate KSHV lytic replication remain largely unknown. In this study, we report that ORF48, a previously identified negative regulator of the cGAS/STING pathway, is required for optimal KSHV lytic replication. We used both siRNA and deletion-based systems to evaluate the importance of intact ORF48 in the KSHV lytic cycle. In both systems, loss of ORF48 resulted in defects in lytic gene transcription, lytic protein expression, viral genome replication and infectious virion production. ORF48 genome deletion caused more robust and global repression of the KSHV transcriptome, possibly due to the disruption of RTA promoter activity. Mechanistically, overexpressed ORF48 was found to colocalize and interact with endogenous STING in HEK293 cells. Endogenous ORF48 and STING interactions were also detected in reactivated iSLK.219 cells. Compared with the control cell line, HUVEC cells stably expressing ORF48 exhibited repressed STING-dependent innate immune signaling upon ISD or diABZI treatment. However, the loss of ORF48 in our iSLK-based lytic system failed to induce IFNß production, suggesting a redundant role of ORF48 on STING signaling during the KSHV lytic phase. Thus, ORF48 is required for optimal KSHV lytic replication through additional mechanisms that need to be further explored.

Vitamin D supplementation and falls in residential aged care: A longitudinal multisite cohort study.

Background: Vitamin D is vital for musculoskeletal health, and supplementation may lower risk of falls. Past research in residential aged care (RAC) settings on the effects of vitamin D on falls have reported inconclusive findings, partly due to study design limitations. We utilised a longitudinal study design to assess the association between the use of vitamin D and falls over 36 months in RAC. Method: A longitudinal cohort study was conducted using routinely collected electronic data spanning 9 years from 27 RAC facilities in Sydney, New South Wales, Australia. The study included 4520 permanent residents aged 65 years or older who were admitted for the first time from 1 July 2014 and stayed for a minimum of one month. We identified daily vitamin D usage over 36 months, and measured adherence using the Proportion of Days Covered (PDC) metric. A PDC value of ≥80 % signifies optimal adherence. Primary outcomes were the number of all falls and injurious falls. A rolling time-varying predictor-outcome approach and Generalized Estimating Equations (GEE) were applied to determine the longitudinal link between vitamin D supplement use and subsequent risk of falls. Results: Over two-thirds of residents (67.8 %; n = 3063) received vitamin D supplements during their stay, with a median PDC of 74.8 % among users, and 44.6 % (n = 1365) achieving optimal adherence. Increasing age, osteoporosis or fracture history, and dementia were associated with a greater likelihood of achieving optimal adherence. Crude fall incident rates were 8.05 and 2.92 incidents per 1000 resident days for all falls and injurious falls respectively. After accounting for relevant demographic and clinical factors, no significant links were observed between vitamin D supplement usage and fall outcomes: all falls (Incident Rate Ratio [IRR] 1.01; 95 % CI 1.00-1.02; P = 0.237) and injurious falls (IRR 1.01; 95 % CI 1.00-1.02; P = 0.091). Conclusion: Vitamin D supplementation was not associated with a reduced risk of falls, suggesting it is not an effective intervention for preventing falls in RAC. While clinicians should ensure adequate vitamin D intake for residents' nutritional and bone health, it should not be a standalone falls prevention intervention in RAC populations.

Beat-to-beat blood pressure variability, hippocampal atrophy, and memory impairment in older adults.

Visit-to-visit blood pressure variability (BPV) predicts age-related hippocampal atrophy, neurodegeneration, and memory decline in older adults. Beat-to-beat BPV may represent a more reliable and efficient tool for prospective risk assessment, but it is unknown whether beat-to-beat BPV is similarly associated with hippocampal neurodegeneration, or with plasma markers of neuroaxonal/neuroglial injury. Independently living older adults without a history of dementia, stroke, or other major neurological disorders were recruited from the community (N = 104; age = 69.5 ± 6.7 (range 55-89); 63% female). Participants underwent continuous blood pressure monitoring, brain MRI, venipuncture, and cognitive testing over two visits. Hippocampal volumes, plasma neurofilament light, and glial fibrillary acidic protein levels were assessed. Beat-to-beat BPV was quantified as systolic blood pressure average real variability during 7-min of supine continuous blood pressure monitoring. The cross-sectional relationship between beat-to-beat BPV and hippocampal volumes, cognitive domain measures, and plasma biomarkers was assessed using multiple linear regression with adjustment for demographic covariates, vascular risk factors, and average systolic blood pressure. Elevated beat-to-beat BPV was associated with decreased left hippocampal volume (P = .008), increased plasma concentration of glial fibrillary acidic protein (P = .006), and decreased memory composite score (P = .02), independent of age, sex, average systolic blood pressure, total intracranial volume, and vascular risk factor burden. In summary, beat-to-beat BPV is independently associated with decreased left hippocampal volume, increased neuroglial injury, and worse memory ability. Findings are consistent with prior studies examining visit-to-visit BPV and suggest beat-to-beat BPV may be a useful marker of hemodynamic brain injury in older adults.

Analysis of Longitudinal Patterns and Predictors of Medicine Use in Residential Aged Care Using Group-Based Trajectory Modeling: The "MEDTRAC-Cardiovascular" Longitudinal Cohort Study.

AIM: Cardiovascular diseases are the leading cause of death globally. Ensuring ongoing use of medicines-medication persistence-is crucial, yet no prior studies have examined this in residential aged care facilities (RACFs). We aimed to identify long-term trajectories of persistence with cardiovascular medicines and determine predictors of persistence trajectories. METHOD: A longitudinal cohort study of 2837 newly admitted permanent residents from 30 RACFs in New South Wales, Australia. We monitored weekly exposure to six cardiovascular medicine classes-lipid modifiers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs), beta-blockers, diuretics, calcium channel blockers (CCB), and cardiac therapy-over 3 years. Group-based trajectory modeling was employed to determine persistence trajectories for each class. RESULTS: At baseline, 76.6% (n = 2172) received at least one cardiovascular medicine with 41.2% receiving lipid modifiers, 31.4% ACEI/ARBs, 30.2% beta-blockers, 24.4% diuretics, 18.7% CCBs, and 14.8% cardiac therapy. The model identified two persistence trajectories for CCBs and three trajectories for all other classes. Sustained high persistence rates ranged from 68.4% (ACEI/ARBs) to 79.8% (beta-blockers) while early decline in persistence and subsequent discontinuation rates ranged from 7.6% (cardiac therapy) to 25.3% (CCBs). Logistic regressions identified 11 predictors of a declining persistence across the six medicine classes. CONCLUSION: Our study revealed varied patterns of cardiovascular medicine use in RACFs, with 2-3 distinctive medicine use trajectories across different classes, each exhibiting a unique clinical profile, and up to a quarter of residents discontinuing a medicine class. Future studies should explore the underlying reasons and appropriateness of nonpersistence to aid in identifying areas for improvement.

Health Care Resource Use for Modern First-Line Treatments in Metastatic Renal Cell Carcinoma.

Importance: Immuno-oncology agents have changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). Such therapies improve survival but can impose considerable health care resource use (HCRU) and associated costs, necessitating their examination. Objective: To compare HCRU, costs, and clinical outcomes among patients receiving first-line pembrolizumab plus axitinib (P+A) or ipilimumab plus nivolumab (I+N). Design, Setting, and Participants: This retrospective cohort study used data from an administrative claims database on patients with mRCC receiving first-line P+A or I+N that was initiated between January 2018 and May 2020. Data were analyzed from February 2021 to July 2022. Exposure: First-line P+A or I+N. Main Outcome and Measures: HCRU and costs during the first 90 days, full first-line treatment, and full follow-up periods were assessed. Using Kaplan-Meier analysis, time on treatment, overall survival, time to first emergency department (ED) visit, and time to first inpatient stay were compared. Results: Among 507 patients, there were 126 patients receiving P+A (91 male [72.2%]; mean [SD] age, 67.93 [9.66] y) and 381 patients receiving I+N (271 male [71.1%]; mean [SD] age, 66.52 [9.94] years). The median time on treatment was longer for the P+A compared with I+N group (12.4 months [95% CI, 8.40 months to not estimable] vs 4.1 months [95% CI, 3.07 to 5.30 months]; P < .001). The median time to first ED visit was longer for the P+A than I+N group (7.2 months [95% CI 3.9 to 11.1 months ] vs 3.3 months [95% CI, 2.6 to 3.9 months]; P = .005), as was time to first inpatient stay (9.0 months [95% CI 6.5 months to not estimable] vs 5.6 months [95% CI, 3.9 to 7.9 months]; P = .02). During the first 90 days, a lower proportion of the P+A than N+I group had ED visits (43 patients [34.1%] vs 182 patients [47.8%] and inpatient stays (24 patients [19.1%) vs144 patients [37.8%]; P < .001). During full follow-up, mean total adjusted costs were similar for P+A and I+N groups, but adjusted 12-month estimated total costs were higher for P+A than I+N groups ($325 574 vs $ 263 803; P = .03). Conclusions and Relevance: In this study, treatment with P+A was associated with longer time on treatment, time to first ED visit, and inpatient stay, while 12-month estimated costs were higher for the P+A group. This is among the first clinical studies to evaluate economic burden associated with modern treatments for mRCC.

Diabetes in residential aged care: Pharmacological management and concordance with clinical guidelines.

OBJECTIVE: Existing studies have highlighted suboptimal diabetes management in residential aged care facilities (RACFs). However, understanding of diabetes management in Australian metropolitan RACFs has been limited. This retrospective cohort study aimed to explore the pharmacological management of diabetes in 25 RACFs in Sydney Australia and assess concordance with clinical practice guidelines (CPGs). METHODS: Data from 231 permanent RACF residents aged ≥65 years and over with type 2 diabetes mellitus over the period from 1 July 2016 to 31 December 2019 were used. Concordance was measured by assessing the medications and medical history data for each individual resident for concordance with evidence-based CPGs. Multivariable logistic regression was used to estimate the effect of resident characteristics on concordance with CPGs. RESULTS: Of the 231 residents with diabetes, 87 (38%) were not taking any antidiabetic medication. Pharmacological management inconsistent with CPG recommendations was observed for 73 (32%) residents, with the most common reason for non-concordance being the use of medications with significant adverse effects in older adults (47, 2%). Residents with hypertension or other heart diseases in addition to their diabetes had greater odds of their diabetes management being non-concordant with CPGs (OR = 2.84 95% CI = 1.54, 5.3 and OR = 2.64, 95% CI = 1.07, 6.41, respectively). CONCLUSIONS: Pharmacological diabetes management in metropolitan Australian RACFs is suboptimal, with a high prevalence of inconsistency with CPGs (32%) observed. Additionally, having hypertension or heart diseases significantly increased the possibility of non-concordance among diabetic RACF residents. Further investigation into the underlying relationships with comorbidities is required to develop better strategies.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment. Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest. Results: Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors. Conclusion: Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.

A Longitudinal Study of the Use and Effects of Fall-Risk-Increasing Drugs in Residential Aged Care.

OBJECTIVES: Fall-risk-increasing drugs (FRIDs)-psychotropics and cardiovascular disease (CVD) drugs-may elevate the risk of falling, with strong evidence observed in psychotropic FRIDs, whereas findings from cardiovascular disease (CVD) FRIDs remain inconclusive. Existing studies on FRIDs and falls are often hampered by methodologic limitations. Leveraging longitudinal observational data, we aimed to determine the long-term patterns of FRID use and their association with falls in residential aged care (RAC) homes. DESIGN: A retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: A total of 4207 permanent residents newly admitted to 27 RAC homes in Sydney, Australia. METHOD: The outcomes were incidence of all and injurious falls. We measured exposure to each FRID over 60 months using the Proportion of Days Covered (PDC) metric. We used group-based multitrajectory modeling to determine concurrent usage patterns of psychotropics and CVD FRIDs and applied negative binomial regression to assess their associations with the outcomes. RESULTS: A total of 83.6% (n = 3516) and 77.3% (n = 3254) residents used psychotropic and CVD FRIDs, respectively. The PDC values ranged from 67.3% (opioids) to 86.9% (antidepressants) for specific psychotropics and 79.0% (α-adrenoceptor antagonists) to 89.6% (ß blockers) for CVD FRIDs. We identified 4 groups: group 1, low psychotropics-low CVDs use (16.7%, n = 701); group 2, low psychotropics-high CVDs (25.0%, n = 1054); group 3, high psychotropics-high CVDs (41.0%, n = 1723); and group 4, high psychotropics-low CVDs (17.3%, n = 729). Group 4 had a significantly higher rate of falls than the other groups for both outcomes, including relative to group 3, in which exposure to both FRID classes was high. CONCLUSIONS AND IMPLICATIONS: Our findings reveal concerningly high FRID use in RAC homes and highlight a critical difference in the impact of the 2 major FRID classes on falls. Psychotropics were strongly associated with falls, whereas the studied CVD FRIDs did not elevate risk of falling.

Tailoring communication practices to support effective delivery of telehealth in general practice.

BACKGROUND: The unprecedented increase in telehealth use due to COVID-19 has changed general practitioners' (GP) and patients' engagement in healthcare. There is limited specific advice for effective communication when using telehealth. Examining telehealth use in practice in conjunction with perspectives on telehealth as they relate to communication allows opportunities to produce evidence-based guidance for optimal use of telehealth, while also offering practitioners the opportunity to reflect on elements of their communicative practice common to both styles of consultation. The objective of this research was to develop evidence-based resources to support effective, person-centred communication when GPs and patients use telehealth. This included examination of interactional practices of recorded telehealth consultations, exploration of GP and patient perspectives relating to telehealth, and identifying priorities for guidance informed by these analyses as well as participant co-design. METHODS: This study involved recording telehealth consultations (n = 42), conducting patient surveys (n = 153), and interviewing patients (n = 9) and GPs (n = 15). These were examined using interaction analytic methods, quantitative analysis, and thematic analyses, to create a robust, integrated picture of telehealth practice and perspectives. The process of research translation involved a co-design approach, engaging with providers, patients, and policy makers to facilitate development of evidence-based principles that focus on supporting effective communication when using telehealth. RESULTS: Three key themes relating to communication in telehealth were identified across the different analyses. These were relationship building, conversational flow, and safety netting. The draft best practice principles drawn from these themes were modified based on co-design feedback into five Best Practice Principles for Communication between GPs and Patients using Telehealth. CONCLUSIONS: Effective communication is supported through relationship building and attention to conversational flow in telehealth consultations, which in turn allows for safety netting to occur. In telehealth, GPs and patients recognise that not being co-present changes the consultation and use both intuitive and strategic interactional adjustments to support their exchange. The mixed-method examination of experiences through both a detailed analysis of telehealth consultations in practice and comparative exploration of GP and patient perspectives enabled the identification of principles that can support effective communication when using telehealth. Co-design helped ensure these principles are ready for implementation into practice.

Short-term blood pressure variability and brain functional network connectivity in older adults.

Background: Blood pressure variability is increasingly linked with cerebrovascular disease and Alzheimer's disease, independent of mean blood pressure levels. Elevated blood pressure variability is also associated with attenuated cerebrovascular reactivity, which may have implications for functional hyperemia underpinning brain network connectivity. It remains unclear whether blood pressure variability is related to functional network connectivity. We examined relationships between beat-to-beat blood pressure variability and functional connectivity in brain networks vulnerable to aging and Alzheimer's disease. Methods: 53 community-dwelling older adults (mean [SD] age = 69.9 [7.5] years, 62.3% female) without history of dementia or clinical stroke underwent continuous blood pressure monitoring and resting state fMRI scan. Blood pressure variability was calculated as variability independent of mean. Functional connectivity was determined by resting state fMRI for several brain networks: default, salience, dorsal attention, fronto-parietal, and language. Multiple linear regression examined relationships between short-term blood pressure variability and functional network connectivity. Results: Elevated short-term blood pressure variability was associated with lower functional connectivity in the default network (systolic: standardized ß = -0.30 [95% CI -0.59, -0.01], p = .04). There were no significant associations between blood pressure variability and connectivity in other functional networks or between mean blood pressure and functional connectivity in any network. Discussion: Older adults with elevated short-term blood pressure variability exhibit lower resting state functional connectivity in the default network. Findings support the role of blood pressure variability in neurovascular dysfunction and Alzheimer's disease. Blood pressure variability may represent an understudied early vascular risk factor for neurovascular dysfunction relevant to Alzheimer's disease, with potential therapeutic implications.

Perception of middle-aged and older adults towards mHealth apps: A comparative factor analysis between Australia and Germany.

OBJECTIVE: Although evidence of the global effectiveness and usability of mobile health (mHealth) apps as non-drug interventions is growing, older adults often demonstrate low adoption rates of these apps. This study aims to identify the perspectives of older adults on introducing and adopting mHealth apps in Australia and Germany. MATERIALS AND METHODS: We conducted two online cross-sectional surveys to examine factors from contextual, technological and personal perspectives that influence older adults in mHealth app adoption. Using descriptive statistics, chi-square tests and exploratory factor analysis, we identified the differences and similarities between respondents' perspectives across two countries. RESULTS: A total of 290 respondents (149, Australia; 141, Germany) completed the survey. Older adults' ability to use a mHealth app, the user-friendliness of the app, their positive self-efficacy regarding their health and resource availability for using mHealth apps were related to intended adoption. Differences between Germany and Australia were found in issues concerned with data sharing and empowerment by the doctor, while similarities were related to trust in the doctor and their treatment approaches. DISCUSSION AND CONCLUSION: This study highlights participants' perspectives and attitudes towards mHealth app use, unmet needs and barriers, and the facilitating influences in the two countries. These insights can be used to inform the development and implementation of mHealth apps and to construct tailored strategies to increase the adoption rates of mHealth apps among older adults and to maximise their potential benefits.

The interactive effect of intra-beat and inter-beat blood pressure variability on neurodegeneration in older adults.

Blood pressure variability (BPV) and arterial stiffness are age-related hemodynamic risk factors for neurodegenerative disease, but it remains unclear whether they exert independent or interactive effects on brain health. When combined with high inter-beat BPV, increased intra-beat BPV indicative of arterial stiffness could convey greater pressure wave fluctuations deeper into the cerebrovasculature, exacerbating neurodegeneration. This interactive effect was studied in older adults using multiple markers of neurodegeneration, including medial temporal lobe (MTL) volume, plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Older adults (N=105) without major neurological or systemic disease were recruited and underwent brain MRI and continuous BP monitoring to quantify inter-beat BPV through systolic average real variability (ARV) and intra-beat variability through arterial stiffness index (ASI). Plasma NfL and GFAP were assessed. The interactive effect of ARV and ASI on MTL atrophy, plasma NfL, and GFAP was studied using hierarchical linear regression. Voxel-based morphometry (VBM) was used to confirm region-of-interest analysis findings. The interaction between higher ARV and higher ASI was significantly associated with left-sided MTL atrophy in both the region-of-interest and false discovery rate-corrected VBM analysis. The interactive effect was also significantly associated with increased plasma NfL, but not GFAP. The interaction between higher ARV and higher ASI is independently associated with increased neurodegenerative markers, including MTL atrophy and plasma NfL, in independently living older adults. Findings could suggest the increased risk for neurodegeneration associated with higher inter-beat BPV may be compounded by increased intra-beat variability due to arterial stiffness.

Co-production processes for translation and validation of psychosocial assessments for older adults in aged care.

OBJECTIVE: Given the diverse ethnic backgrounds of aged care clients, there is a critical requirement to translate psychosocial assessment tools into various languages to effectively evaluate social engagement and quality of life in older adults receiving aged care services. This study aimed to translate psychosocial tools into Turkish, Korean and Mandarin, the primary languages spoken by clients of an Australian community aged care provider. METHODS: A co-development approach encompassing forward and backward translations of the Australian Community Participation Questionnaire and ICEpop CAPability measure for Older people tools, along with focus group discussions involving bilingual staff (n = 7) and clients (n = 16), was employed to ensure precision and cultural relevance. Multiple iterations were undertaken until linguistic, conceptual and scaling equivalence was achieved, with recorded sessions transcribed and analysed thematically. RESULTS: Cultural appropriateness significantly impacted the delivery of questions within the tools, emphasising translation challenges tied to specific queries. These difficulties included the lack of terms for unique places of worship, the use of outdated language (e.g., references to reading newspapers), and varying priorities in social and well-being matters between Western and Eastern/Asian cultures. Staff feedback identified that formal translated tool versions eased administration for culturally and linguistically diverse (CALD) clients, enabling them to independently interpret questions, resulting in improved questionnaire completion rates. CONCLUSIONS: Insights indicate the need for continued efforts in tailoring assessment tools to diverse cultural contexts to ensure accurate and meaningful data collection.

Adverse impacts in residential aged care facilities: The resident perspective.

OBJECTIVES: Inclusion of consumer perspectives is a key component to person-centred health-care approaches. While current residential aged care systems focus on recording adverse events to meet the requirements of regulatory reporting, little is known about the views of residents. The aim of this research was to explore residents' responses on the types of incidents that have an adverse impact on them and how they are affected by these incidents. METHODS: The study used a qualitative, inductive approach to derive themes from interviews with 20 permanent residents of aged care facilities in New South Wales and the Australian Capital Territory. RESULTS: Four main themes surrounding adverse incidents emerged: (i) social relationships and the adverse impacts of lack of meaningful interactions, (ii) adjustment to life in the residential aged care facility and the loss of residents' former life and self-determination, (iii) the impact of COVID-19 lockdowns which meant that residents were not able to go out or interact with others and (iv) acceptance, resignation and resilience in coping with adverse incidents. CONCLUSIONS: This research highlights the difference between health-care definition, used for incident management reporting and quality indicators, and the way residents respond when asked to describe an incident that has affected them. Resident responses discuss situations having an adverse effect on them in contrast to the way adverse events and incidents are reported and monitored. The findings suggest that within adverse event and incident management systems and resident governance systems, there is scope for incorporating periods of transitions and well-being measures that capture elements that matter to older people.

The relationship between participation in leisure activities and incidence of falls in residential aged care.

BACKGROUND: Active engagement in leisure activities has positive effects on individuals' health outcomes and social functioning; however, there is limited understanding of the link between participation in leisure activities, particularly non-exercise activities, and falls in older adults. This study aimed to determine the relationship between participation in leisure activities and the incidence of falls, and the variation of this relationship by dementia status in residential aged care facilities (RACFs). METHODS: A retrospective longitudinal cohort study utilising routinely collected data (January 2021-August 2022) from 25 RACFs in Sydney, Australia, was conducted. The cohort included 3,024 older permanent residents (1,493 with dementia and 1,531 without) aged ≥65 and with a stay of ≥1 week. The level of participation in leisure activities was measured using the number of leisure activities per 1,000 resident days and divided into quartiles. Outcome measures were the incidence rate of all falls and injurious falls (i.e., number of falls per 1,000 resident days). We used multilevel negative binary regression to examine the relationship between leisure participation and fall incidence. RESULTS: For the whole sample, leisure participation was significantly inversely associated with the incidence rate of all falls and injurious falls. For example, residents in the high leisure participation group were 26% less likely to experience a fall compared to those in the low leisure participation group after controlling for confounders (incidence rate ratio = 0.74, 95% confidence interval = 0.60, 0.91). Such inverse relationship was observed in both exercise and non-exercise activities and was stronger among residents without dementia. CONCLUSIONS: Leisure participation is associated with a lower rate of falls, a key quality indicator by which RACFs are benchmarked and funded in Australia and many other countries. More recognition and attention are needed for the currently underfunded leisure activities in RACFs in future funding arrangement.

Real-world utilization, patient characteristics, and treatment patterns among men with localized prostate cancer tested with the 17-gene genomic prostate score® (GPSTM) assay.

OBJECTIVES: Descriptive study focusing on real-world utilization and characteristics of men with prostate cancer tested with the 17-gene Genomic Prostate Score® (GPS™) assay by linking administrative claims and electronic health record (EHR) data with GPS results. METHODS: This retrospective, observational cohort study (January 1, 2013 to December 31, 2020) included men aged 40-80 years with localized prostate cancer claims, continuous enrollment in Optum's Integrated Claims data set, ≥1 day of EHR clinical activity, and a GPS result. Men were classified as undergoing definitive therapy (DT) (prostatectomy, radiation, or focal therapy) or active surveillance (AS). AS and DT distribution were analyzed across GPS results, National Comprehensive Cancer Network® (NCCN®) risk, and race. Costs were assessed 6 months after the first GPS result (index); clinical outcomes and AS persistence were assessed during the variable follow-up. All variables were analyzed descriptively. RESULTS: Of 834 men, 650 (77.9%) underwent AS and 184 (22.1%) DT. Most men had Quan-Charlson comorbidity scores of 1-2 and a tumor stage of T1c (index). The most common Gleason patterns were 3 + 3 (79.6%) (AS cohort) and 3 + 4 (55.9%) (DT cohort). The mean (standard deviation) GPS results at index were 23.2 (11.3) (AS) and 30.9 (12.9) (DT). AS decreased with increasing GPS result and NCCN risk. Differences between races were minimal. Total costs were substantially higher in the DT cohort. CONCLUSIONS: Most men with GPS-tested localized prostate cancer underwent AS, indicating the GPS result can inform clinical management. Decreasing AS with increasing GPS result and NCCN risk suggests the GPS complements NCCN risk stratification.

ORF48 is required for optimal lytic replication of Kaposi's Sarcoma-Associated Herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes persistent infection in the host by encoding a vast network of proteins that aid immune evasion. One of these targeted innate immunity pathways is the cGAS-STING pathway, which inhibits the reactivation of KSHV from latency. Previously, we identified multiple cGAS/STING inhibitors encoded by KSHV, suggesting that the counteractions of this pathway by viral proteins are critical for maintaining a successful KSHV life cycle. However, the detailed mechanisms of how these viral proteins block innate immunity and facilitate KSHV lytic replication remain largely unknown. In this study, we report that ORF48, a previously identified negative regulator of the cGAS/STING pathway, is required for optimal KSHV lytic replication. We used both siRNA and deletion-based systems to evaluate the importance of intact ORF48 in the KSHV lytic cycle. In both systems, loss of ORF48 resulted in defects in lytic gene transcription, lytic protein expression, viral genome replication and infectious virion production. ORF48 genome deletion caused more robust and global repression of the KSHV transcriptome, possibly due to the disruption of RTA promoter activity. Mechanistically, overexpressed ORF48 was found to interact with endogenous STING in HEK293 cells. Compared with the control cell line, HUVEC cells stably expressing ORF48 exhibited repressed STING-dependent innate immune signaling upon ISD or diABZI treatment. However, the loss of ORF48 in our iSLK-based lytic system failed to induce IFNß production, suggesting a redundant role of ORF48 on STING signaling during the KSHV lytic phase. Thus, ORF48 is required for optimal KSHV lytic replication through additional mechanisms that need to be further explored.

Effectiveness of fall prevention interventions in residential aged care and community settings: an umbrella review.

INTRODUCTION: Preventing falls is a priority for aged care providers. Research to date has focused on fall prevention strategies in single settings (e.g., residential aged care (RAC) or community settings). However, some aged care providers deliver care, including fall prevention interventions, across RAC and community settings. We conducted an umbrella review to identify what type of fall prevention interventions had the greatest impact on falls outcomes in RAC and community settings. METHODS: Five databases were searched for systematic reviews of falls prevention randomised control trials in older adults living in the community or RAC. Data extracted included systematic review methods, population characteristics, intervention characteristics, setting details (RAC or community), and fall-related outcomes (falls, people who have had a fall, fall-related hospitalisations, and fall-related fractures). Review quality was appraised using the Assessment of Multiple Systematic Reviews-2 tool. RESULTS: One-hundred and six systematic reviews were included; 63 and 19 of these stratified results by community and RAC settings respectively, the remainder looked at both settings. The most common intervention types discussed in reviews included 'exercise' (61%, n = 65), 'multifactorial' (two or more intervention types delivered together) (26%, n = 28), and 'vitamin D' (18%, n = 19). In RAC and community settings, 'exercise' interventions demonstrated the most consistent reduction in falls and people who have had a fall compared to other intervention types. 'Multifactorial' interventions were also beneficial in both settings however demonstrated more consistent reduction in falls and people who fall in RAC settings compared to community settings. 'Vitamin D' interventions may be beneficial in community-dwelling populations but not in RAC settings. It was not possible to stratify fall-related hospitalisation and fall-related fracture outcomes by setting due to limited number of RAC-specific reviews (n = 3 and 0 respectively). CONCLUSION: 'Exercise' interventions may be the most appropriate falls prevention intervention for older adults in RAC and community settings as it is beneficial for multiple fall-related outcomes (falls, fall-related fractures, and people who have had a fall). Augmenting 'exercise' interventions to become 'multifactorial' interventions may also improve the incidence of falls in both settings.