Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults

Risk of chronic kidney disease (CKD) is influenced by environmental and genetic factors and increases sharply in individuals 70 years and older. Polygenic scores (PGS) for kidney disease-related traits have shown promise but require validation in well-characterized cohorts. Here, we assessed the performance of recently developed PGSs for CKD-related traits in a longitudinal cohort of healthy older individuals enrolled in the Australian ASPREE randomized controlled trial of daily low-dose aspirin with CKD risk at baseline and longitudinally. Among 11,813 genotyped participants aged 70 years or more with baseline eGFR measures, we tested associations between PGSs and measured eGFR at baseline, clinical phenotype of CKD, and longitudinal rate of eGFR decline spanning up to six years of follow-up per participant. A PGS for eGFR was associated with baseline eGFR, with a significant decrease of 3.9 mL/min/1.73m2 (95% confidence interval -4.17 to -3.68) per standard deviation (SD) increase of the PGS. This PGS, as well as a PGS for CKD stage 3 were both associated with higher risk of baseline CKD stage 3 in cross-sectional analysis (Odds Ratio 1.75 per SD, 95% confidence interval 1.66-1.85, and Odds Ratio 1.51 per SD, 95% confidence interval 1.43-1.59, respectively). Longitudinally, two separate PGSs for eGFR slope were associated with significant kidney function decline during follow-up. Thus, our study demonstrates that kidney function has a considerable genetic component in older adults, and that new PGSs for kidney disease-related phenotypes may have potential utility for CKD risk prediction in advanced age

Sleep-disordered breathing was associated with lower health-related quality of life and cognitive function in a cross-sectional study of older adults

BACKGROUND AND OBJECTIVE: The clinical significance of sleep‐disordered breathing (SDB) in older age is uncertain. This study determined the prevalence and associations of SDB with mood, daytime sleepiness, quality of life (QOL) and cognition in a relatively healthy older Australian cohort. METHODS: A cross‐sectional analysis was conducted from the Study of Neurocognitive Outcomes, Radiological and retinal Effects of Aspirin in Sleep Apnoea. Participants completed an unattended limited channel sleep study to measure the oxygen desaturation index (ODI) to define mild (ODI 5–15) and moderate/severe (ODI ≥ 15) SDB, the Centre for Epidemiological Studies Scale, the Epworth Sleepiness Scale, the 12‐item Short‐Form for QOL and neuropsychological tests. RESULTS: Of the 1399 participants (mean age 74.0 years), 36% (273 of 753) of men and 25% (164 of 646) of women had moderate/severe SDB. SDB was associated with lower physical health‐related QOL (mild SDB: beta coefficient [β] −2.5, 95% CI −3.6 to −1.3, p < 0.001; moderate/severe SDB: β −1.8, 95% CI −3.0 to −0.6, p = 0.005) and with lower global composite cognition (mild SDB: β −0.1, 95% CI −0.2 to 0.0, p = 0.022; moderate/severe SDB: β −0.1, 95% CI −0.2 to 0.0, p = 0.032) compared to no SDB. SDB was not associated with daytime sleepiness nor depression. CONCLUSION: SDB was associated with lower physical health‐related quality of life and cognitive function. Given the high prevalence of SDB in older age, assessing QOL and cognition may better delineate subgroups requiring further management, and provide useful treatment target measures for this age group

Severe low back or lower limb pain is associated with recurrent falls among older Australians

Background: Few studies have explored the impact of low back or lower limb pain severity on recurrent (≥2) falls in older adults. Objectives: Investigate the association between the severity of low back or lower limb pain, and ≥2 falls or falls-related injuries. Methods: Community-dwelling Australian males and females in the ASPREE Longitudinal Study of Older Persons (ALSOP), aged ≥70 years. Self-reported, cross-sectional questionnaire data regarding number of falls and falls-related injuries in the last 12 months; and sites and severity of pain experienced on most days. Adjusted relative risks (RR) were estimated from multivariable Poisson regression models, for males and females separately. Results: Of 14,892 ALSOP participants, 13% (n = 1983) reported ≥2 falls (‘recurrent fallers’) in the last 12 months. Males and females who reported severe low back, or severe lower limb pain on most days were more likely to report ≥2 falls in the last 12 months compared to those with mild pain (lower back: males RR = 1.70 and females RR = 1.5, p = 0.001; lower limb: males RR = 2.0, p < 0.001 and females RR = 1.4, p = 0.003). Female recurrent fallers who reported severe low back (RR = 1.3, p = 0.029) or lower limb (RR = 1.2, p = 0.024) pain on most days were more likely to report a falls-related injury in the last 12 months compared to females with mild pain. Conclusion: Severe low back or lower limb pain was associated with an increased likelihood of recurrent falls (males/females) or falls-related injuries (females only). Assessment of severe low back and lower limb pain should be considered as a priority when undertaking falls-risk evaluation. Significance: Severe low back pain, or severe lower limb pain is associated with an increased likelihood of recurrent falls in older males and females, and an increased likelihood of falls-related injuries in older female recurrent fallers. Assessment and management of severe low back and lower limb pain should be prioritized when undertaking falls-risk assessment. Future longitudinal research is required to further interrogate this relationship and its underlying mechanisms

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

<p>Abstract</p> <p>Background</p> <p>The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression.</p> <p>Methods/Design</p> <p>The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm²or >10 cm². Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process.</p> <p>Discussion</p> <p>The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes.</p> <p>Trial Registration</p> <p>ACTRN12608000599370</p

Effect of aspirin on cancer incidence and mortality in older adults.

BACKGROUND: ASPirin in Reducing Events in the Elderly (ASPREE), a randomized double-blind placebo-controlled trial (RCT) of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast prior RCTs, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. METHODS: 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia or physical disability were randomized and followed for a median of 4.7 years. Fatal and non-fatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. RESULTS: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (HR = 1.04, 95% CI = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). CONCLUSIONS: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and thus, suggest caution with its use in this age group

Prediction of disability-free survival in healthy older people.

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583)

Biospecimens in FDO world

With the advent of technological advances in research settings, scientific collections including sample material became on par with big data. Consequently there is a widespread need to highlight and recognise the inherent value of samples coupled with efforts in unlocking sample potential as resources for new scientific discovery. Samples with informative metadata can be more easily discoverable, more readily shared and reused, allowing reanalysis of associated datasets, avoiding duplicate efforts, and providing metaanalysis yielding considerably enhanced insight. Metadata provides the framework for a consistent, systematic and standardized collection of sample information, enabling users to identify the availability of research output from the samples, relevancy to their intended use, and a way to conveniently identify sample material as well as access provenance information related to the physical samples. Researchers need this essential information aiding their decision making process on the quality, usability and accessibility of the samples and associated datasets. We propose to explore the practical implementation of FAIR Digital Objects (FDO) for biological life science physical samples and practically how to create an FDO framework centralized around biospecimen samples, linked datasets, sample information and PIDs (Persistent Identifiers)Klump et al. 2021. This effort is highly relevant to enhancing the portability of sample information between multiple repositories and other kinds of resources (e.g. e-infrastructures).In this session we would like to present our current work in order to mobilize the community to define the FAIR Digital Object Architecture for biospecimen in life science including all infrastructure components e.g. metadata, PIDs and their integration with technical solutions. To that end, in our community of practice we aim to:What: Identify the minimum set of attributes required for describing biospecimen in biological life science (Minimal Information About a Biological Sample, MIABS) with ontological mapping for semantic unambiguity and machine actionability.Identify the required attributes for registering PIDs for biospecimens and how that will operate in an FDO ecosystem. This will pave the way for a framework of coupling the descriptive metadata to the digital object in a FAIR and comprehensive manner.How:Define a semantic FDO model for biospecimens.Define the role of biospecimen PIDs registration information and kernel attributes and how that translates to machine actionability and programmatic decisions.Define the implementation specifics for integration of biospecimen FDOs with operational infrastructure e.g. e-infrastructures, repositories and machines.Relevant technologies include: RO-Crate, Persistent identifiers, and metadata schemas The recent partnership between IGSN and DataCite described below is a catalyst in this call of action to the FDO community to build a Community of Practice (CoP) specifically focused on biospecimen samples. Community of practice:IGSN e.V. announced a partnership with DataCite, in which DataCite’s registration services and supporting technology for Digital Object Identifiers (another type of PID) are now being leveraged to register IGSN IDs, and thus ensure the ongoing sustainability of the IGSN ID infrastructure. Importantly, the two organizations are also focusing the community’s efforts on advocacy of PIDs for physical samples and expanding the global sample ecosystem. Assisted by the DataCite Samples Community Manager, the IGSN e.V. is establishing working groups (Communities of Practice) within different research domains to support development and promotion of standardized methods for identifying, citing, and locating physical samples. In particular, the partnership wishes to work with the Biosamples community to elaborate the necessary information (metadata) such that those within the community have a full understanding of a physical sample when its descriptive webpage is accessed via its PID, see this example

Validity of Unplanned Admission to an Intensive Care Unit as a Measure of Patient Safety in Surgical Patients

Background: An unplanned admission to the intensive care unit within 24 h of a procedure (UIA) is a recommended clinical indicator in surgical patients. Often regarded as a surrogate marker of adverse events, it has potential as a direct measure of patient safety. Its true validity for such use is currently unknown.Methods: The authors validated UIA as an indicator of safety in surgical patients in a prospective cohort study of 44,130 patients admitted to their hospital. They assessed the association of UIA with intraoperative incidents and near misses, increased hospital length of stay, and 30-day mortality as three constructs of patient safety.Results: The authors identified 201 patients with a UIA; 104 (52.2%) had at least one incident or near miss. After adjusting for confounders, these incidents were significantly associated with UIA in all categories of surgical procedures analyzed; odds ratios were 12.21 (95% confidence interval [CI], 6.33-23.58), 4.06 (95% CI, 2.74-6.03), and 2.13 (95% CI, 1.02-4.42), respectively. The 30-day mortality for patients with UIA was 10.9%, compared with 1.1% in non-UIA patients. After risk adjustment, UIA was associated with excess mortality in several types of surgical procedures (odds ratio, 3.89; 95% CI, 2.14-7.04). The median length of stay was increased if UIA occurred: 16 days (interquartile range, 10-31) versus 2 days (interquartile range, 0.5-9) (P Conclusions: These findings provide strong support for the construct validity of UIA as a measure of patient safety.</p