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Brain age is a neuroimaging-based biomarker of aging. This study examined whether the difference between brain age and chronological age (brain-PAD) is associated with cognitive function at baseline and longitudinally. Participants were relatively healthy, predominantly white community-dwelling older adults (n = 531, aged ≥70 years), with high educational attainment (61% ≥12 years) and socioeconomic status (59% ≥75th percentile). Brain age was estimated from T1-weighted magnetic resonance images using an algorithm by Cole et al., 2018. After controlling for age, gender, education, depression and body mass index, brain-PAD was negatively associated with psychomotor speed (Symbol Digit Modalities Test) at baseline (Bonferroni p < 0.006), but was not associated with baseline verbal fluency (Controlled Oral Word Association Test), delayed recall (Hopkins Learning Test Revised), or general cognitive status (Mini-Mental State Examination). Baseline brain-PAD was not associated with 3-year change in cognition (Bonferroni p > 0.006). These findings indicate that even in relatively healthy older people, accelerated brain aging is associated with worse psychomotor speed, but future longitudinal research into changes in brain-PAD is needed.

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65–98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07–.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = −.31) and grip strength (r = −.46), and strongly associated with a modified Fried’s frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6–28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual’s vulnerability to and risk of disease.

Background: Personal sensing may improve digital therapeutics for mental health care by facilitating early screening, symptom monitoring, risk prediction, and personalized/adaptive interventions. However, further development and use of personal sensing first requires better understanding of its acceptability to people targeted for these mental health applications. Objective: We assessed the acceptability of both active and passive personal sensing methods in a sample of people with moderate to severe alcohol use disorder using both behavioral and self-report measures. Method: Participants (N = 154; 50% female; mean age = 41; 87% White, 97% Non-Hispanic) in early recovery (1 – 8 weeks of abstinence) from alcohol use disorder were recruited from the Madison, WI area to participate in a 3-month longitudinal study. Participants engaged with active (ecological momentary assessment; EMA, audio check-in, and sleep quality) and passive (geolocation, cellular communication logs, and text message content) personal sensing methods. We assessed 3 behavioral indicators of acceptability: participants’ choices about their participation in the study at various stages in the study procedure, their choice to opt-in to provide data for each personal sensing method, and their compliance for a subset of the active methods (EMA, audio check-in). We also assessed 3 self-report measures of acceptability (interference, dislike, and willingness to use for 1 year) for each method. Results: All but 1 of the individuals who were eligible to participate consented to the personal sensing procedures. Most of these individuals (88%) also returned 1 week later to formally enroll in the study and begin to provide these data. All participants (100%) opted-in to provide data for EMA, sleep quality, and all passive methods (geolocation, cellular communication logs, text message content). Three participants (2%) did not provide any audio check-ins while on study. The average completion rate for all requested EMAs (4X daily) was 81% for 4x daily and 94% for 1x daily. The completion rate for the daily audio check-in was 55%. Aggregate participant ratings indicated all personal sensing methods to be significantly more acceptable (all P’s < .05) compared to neutral across subjective measures of interference, dislike, and willingness to use for 1 year. Participants did not significantly differ in their dislike of active compared to passive methods (P = .23). However, participants reported a higher willingness to use passive methods for 1 year compared to active methods (P = .04). Conclusions: The results of our study suggest that both active and passive personal sensing methods are generally acceptable to people with alcohol use disorder over a longer period than has previously been assessed. This was true even for data streams that contained potentially more sensitive information (e.g., geolocation, cellular communications). Important individual differences were observed both across people and methods which indicate opportunities for future improvements.

Background:Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug ‐ cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine ‐ are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment.Objectives:To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer‐related outcomes.Search methods:We searched the Cochrane Dementia and Cognitive Improvement Group’s Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources.Selection criteria:We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs.Data collection and analysis:Two review authors independently assessed citations and full‐text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3‐11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods.Main results:We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias.Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) ‐0.42, 95% confidence interval (CI) ‐0.64 to ‐0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD ‐0.40, 95% CI ‐0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD ‐0.62; 95% CI ‐0.94 to ‐0.31). Data from one longer‐term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) ‐2.09 Standardised Mini‐Mental State Examination (SMMSE) points, 95% CI ‐3.43 to ‐0.75; moderate certainty).Discontinuation may make little or no difference to functional status in the short term (SMD ‐0.25, 95% CI ‐0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD ‐0.38, 95% CI ‐0.74 to ‐0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD ‐3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI ‐6.67 to ‐0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD ‐ 0.48, 95% CI ‐0.82 to ‐0.13; 2 studies; low certainty; and SMD ‐0.27, 95% CI ‐0.47 to ‐0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD ‐0.87 Neuropsychiatric Inventory (NPI) points; 95% CI ‐8.42 to 6.68; moderate certainty).We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review.Authors' conclusionsThis review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well‐designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.

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 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.

IntroductionThe world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia.Methods and analysisWe will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models.Ethics and disseminationSTAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences.Trial registration numberNCT02099123.

Objective: Evaluate the Pain Impact Index, a simple, brief, easy-to-use, and novel tool to assess the impact of chronic pain in community-dwelling older adults. Methods: A Rasch modelling analysis was undertaken in Stata using a partial credit model suited to the Likert-type items that comprised the Index. The Index was evaluated for ordering of category thresholds, unidimensionality, overall fit to the Rasch model, measurement bias (Differential Item Functioning, DIF), targeting, and construct validity. Results: The four-item Pain Impact Index was self-completed by 6454 community-dwelling Australians who were aged at least 70 years and experienced pain on most days. Two items showed evidence of threshold disordering, and this was resolved by collapsing response categories (from 5 to 3) for all items. The rescored Index conformed to the unidimensionality assumption and had satisfactory fit with the Rasch model (analyses conducted on a reduced sample size to mitigate the potential for overpowering: n = 377, P > 0.0125, power > 77%). When considering uniform DIF, the most frequent sources of measurement bias were age, knee pain, and upper back pain. When considering nonuniform DIF, the most frequent source of measurement bias was knee pain. The Index had good ability to differentiate between respondents with different levels of pain impact and had highest measurement precision for respondents located around the average level of pain impact in the study sample. Both convergent and discriminant validity of the Index were supported. Conclusion: The Pain Impact Index showed evidence of unidimensionality, was able to successfully differentiate between levels of pain impact, and had good evidence of construct validity.

BACKGROUND There are 20 million living US armed forces veterans; however, the organ donation attitudes of veterans have not been examined. METHODS Over a 17-month period, a convenience sample of 1517 veterans in New England completed a survey to assess attitudes about organ, tissue, and vascularized composite allograft (VCA) donation. RESULTS Most veterans (96%) supported the donation of organs and tissue for transplantation, and 59% were registered as an organ and tissue donor. Being younger (adjusted odds ratio [aOR]: 0.960.970.98; P = 0.01), female (aOR: 1.061.462.03; P = 0.02), non-Hispanic white (aOR: 1.302.073.30; P = 0.01), Hispanic (aOR: 1.282.434.61; P = 0.01), and having more trust that the transplant process is fair and equal (aOR: 1.191.401.65; P = 0.01) were predictive of donor registration. Also, most veterans were willing to donate their face (57%), hands/arms (81%), legs (81%), penis (men: 61%), and uterus (women: 76%) at time of death; donation willingness was higher for upper and lower limbs than for face or genitourinary organs (P < 0.001). Those unwilling to donate VCA organs expressed concerns about identity loss, psychological discomfort of self and others, body integrity, funeral presentation, and religious beliefs. Most (54%) felt that VCA donation should require permission of legal next-of-kin at the time of one's death, even if the decedent was a registered donor. CONCLUSIONS There is a high level of support for organ, tissue, and VCA transplantation and donation among veterans, despite limited educational campaigns targeting this population. There is high potential among veterans to further increase donor registry enrollment and raise awareness about VCA benefits for severely injured service members.

Background Hypersensitivity reactions (HSRs) to tetracyclines and the related compound, tigecycline, can limit the use of these medications and compromise optimal patient care. Despite this, there is little discussion in the literature describing the presentation of these reactions or guiding clinicians on the management of these reactions in adult and pediatric patients. Objective To describe the clinical features, optimal diagnostic approach, and management of HSRs to tetracyclines. Methods Patients with reactions to tetracyclines at our institution from 2011 to 2019 were identified by retrospective chart review. Skin testing protocols were designed for each antibiotic. Graded challenge and desensitization procedures were devised based on medical history, skin testing results when available, and need for readministration. Results The HSRs to tetracyclines, their workup, and management are described for 10 patients, aged 7 to 68 years. Our skin testing protocols for doxycycline, minocycline, and tigecycline described herein had good negative predictive value. When skin testing was negative and the initial reaction was not severe, graded challenge to the culprit drug was performed. Using the included procedures, 3 patients were desensitized to oral doxycycline, 3 to oral minocycline, and 2 to intravenous tigecycline. All the desensitizations were successful. Conclusion Once identified, HSRs to tetracyclines can be further evaluated with skin testing and graded challenge and managed in appropriate cases with desensitization. These procedures can facilitate first-line therapy for patients who require tetracyclines but developed hypersensitivity reactions.

The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ignored to date. In this Perspective, we present a rationale for an urgent need to investigate this possible impact and therapeutic options for COVID-19 based on dietary and microbiome modifications. The mitigating role of nanotechnology with relation to the impact of SARS-CoV-2 virus is highlighted.

ObjectiveTo determine the effect of low-dose aspirin vs placebo on incident all-cause dementia, incident Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive decline in older individuals.MethodsAspirin in Reducing Events in the Elderly (ASPREE) was a double-blind, placebo-controlled trial of low-dose aspirin. In the United States and Australia, community-dwelling individuals aged ≥70 years (US minorities ≥65 years) and free of cardiovascular disease, physical disability, and diagnosed dementia were enrolled. Participants were randomized 1:1–100 mg daily aspirin or placebo. The Modified Mini-Mental State Examination, Hopkins Verbal Learning Test–Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test assessed cognition at baseline and over follow-up. Additional cognitive testing was performed in participants with suspected dementia (“trigger”) based on within-study assessments or clinical history. Dementia was adjudicated according to DSM-IV criteria. National Institute on Aging–Alzheimer’s Association criteria were used for AD and MCI subclassification.ResultsA total of 19,114 participants were followed over a median 4.7 years and 964 triggered further dementia assessments. There were 575 adjudicated dementia cases, and 41% were classified as clinically probable AD. There was no substantial difference in the risk of all dementia triggers (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.91–1.17), probable AD (HR, 0.96; 95% CI, 0.74–1.24), or MCI (HR, 1.12; 95% CI, 0.92–1.37) between aspirin and placebo. Cognitive change over time was similar in the aspirin and placebo groups.ConclusionsThere was no evidence that aspirin was effective in reducing risk of dementia, MCI, or cognitive decline. Follow-up of these outcomes after initial exposure is ongoing.Classification of evidenceThis study provides Class II evidence that for healthy older individuals, low-dose aspirin does not significantly reduce the incidence of dementia, probable AD, MCI, or cognitive decline.Clinicaltrials.gov identifierNCT01038583.

Refereed/Peer-reviewed Background: Studies related to clinical quality indicators (CQIs) in dementia have focused on hospitalizations, medication management, and safety. Less attention has been paid to indicators related to primary and secondary care. OBJECTIVE: To evaluate the incidence of primary and secondary care CQIs for Australians with dementia using government-subsidized aged care. The examined CQIs were: comprehensive medication reviews, 75+ health assessments, comprehensive geriatric assessments, chronic disease management plans, general practitioner (GP) mental health treatment plans, and psychiatrist attendances. Methods: Retrospective cohort study (2011-2016) of 255,458 individuals. National trend analyses estimated incidence rates and 95% confidence intervals (CI) using Poisson or negative binomial regression. Associations were assessed using backward stepwise multivariate Poisson or negative binomial regression model, as appropriate. Funnel plots examined geographic and permanent residential aged care (PRAC) facility variation. Results: CQI incidence increased in all CQIs but medication reviews. For the overall cohort, 75+ health assessments increased from 1.07/1000 person-days to 1.16/1000 person-days (adjusted incidence rate ratio (aIRR) = 1.03, 95% CI 1.02-1.03).Comprehensive geriatric assessments increased from 0.24 to 0.37/1000 person-days (aIRR = 1.12, 95% CI 1.10-1.14). GP mental health treatment plans increased from 0.04 to 0.07/1000 person-days (aIRR = 1.13, 95% CI 1.12-1.15). Psychiatric attendances increased from 0.09 to 0.11/1000 person-days (aIRR = 1.05, 95% CI 1.03-1.07). Being female, older, having fewer comorbidities, and living outside a major city were associated with lower likelihood of using the services. Large geographical and PRAC facility variation was observed (0-92%). Conclusion: Better use of primary and secondary care services to address needs of individuals with dementia is urgently needed.

This research investigates the influence of the commercial photochromic dye concentration, expressed as a percentage, and polymer type and their interaction on the photocoloration properties of the...

The burden of dementia is increasing globally. In the absence of curative treatment, preventive strategies to delay or reduce progression of dementia are crucial. This relies on the identification of modifiable risk factors. The effects of dementia on sleep are well recognized; however, there is now growing evidence suggesting a bidirectional relationship between sleep pathologies and dementia. SDB, poor quality sleep and extremes of sleep duration are commonly experienced by both middle-aged and older populations. All have been associated with increased risk of dementia and cognitive decline in a number of observational studies, albeit inconsistently. The mechanisms by which these sleep disorders may contribute to neurodegeneration are manifold, and include impacts of fragmented sleep on the clearance of neurotoxins, and in SDB by the additive effects of intermittent hypoxia on beta-amyloid production, hypoxic cell death, neuroinflammation and damage to cerebral vasculature. Untangling the mechanisms by which sleep pathologies may impact risk of dementia is a challenge. Many insights into the pathophysiology of these relationships have been derived from animal- and population-based studies. Neuroimaging modalities offer important opportunities to further understand the link between sleep pathologies and dementia risk in vivo, especially in the critical preclinical phase of AD. In this review, we canvas updates in dementia pathophysiology, the evidence linking sleep pathologies with dementia and outline the advances in determining this potential pathophysiological link that have eventuated from the application of neuroimaging.

ImportanceFalls and fractures are frequent and deleterious to the health of older people. Aspirin has been reported to reduce bone fragility and slow bone loss.ObjectiveTo determine if daily low-dose aspirin (100 mg) reduces the risk of fractures or serious falls (fall-related hospital presentations) in healthy older men and women.Design, Setting, and ParticipantsThis substudy of a double-blind, randomized, placebo-controlled trial studied older adult men and women in 16 major sites across southeastern Australia. The ASPREE-FRACTURE substudy was conducted as part of the Australian component of the ASPREE trial. Between 2010 and 2014 healthy (free of cardiovascular disease, dementia or physical disability), community-dwelling volunteers aged 70 years or older were recruited to participate in the ASPREE trial. Potentially eligible participants were identified by medical practitioners and trial personnel and were then sent a letter of invitation to participate. Interested participants were screened for suitability. Eligible participants with medical practitioner authorization and adherent to a 4-week run-in medication trial were randomized. Data were analyzed from October 17, 2019, to August 31, 2022.InterventionsParticipants in the intervention group received a daily dose of oral 100 mg enteric-coated (low-dose) aspirin. The control group received a daily identical enteric-coated placebo tablet.Main Outcomes and MeasuresThe primary outcome of ASPREE-FRACTURE was the occurrence of any fracture. The secondary outcome was serious fall resulting in hospital presentation.ResultsIn total, 16 703 people with a median (IQR) age of 74 (72-78) years were recruited, and 9179 (55.0%) were women. There were 8322 intervention participants and 8381 control participants included in the primary and secondary outcome analysis of 2865 fractures and 1688 serious falls over the median follow-up of 4.6 years. While there was no difference in the risk of first fracture between the intervention and control participants (hazard ratio, 0.97; 95% CI, 0.87-1.06; P = .50), aspirin was associated with a higher risk of serious falls (total falls 884 vs 804; incidence rate ratio, 1.17; 95% CI, 1.03-1.33; P = .01). Results remained unchanged in analyses that adjusted for covariates known to influence fracture and fall risk.Conclusions and RelevanceIn this substudy of a randomized clinical trial, the failure of low-dose aspirin to reduce the risk of fractures while increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.Trial RegistrationThis substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).

The many changes that occur in the lives of older people put them at an increased risk of being socially isolated and lonely. Intergenerational programs for older adults and young children can potentially address this shortfall, because of the perceived benefit from generations interacting. This study explores whether there is an appetite in the community for intergenerational programs for community dwelling older adults. An online survey was distributed via social media, research team networks, and snowballing recruitment with access provided via QR code or hyperlink. Semi-structured interviews were undertaken with potential participants of a pilot intergenerational program planned for the Eastern Suburbs of Sydney, Australia in 2020. The interviews were thematically analyzed. Over 250 people completed the survey, and 21 interviews took place with older adults (10) and parents of young children (11). The data showed that participants were all in favor of intergenerational programs, but there were different perceptions about who benefits most and how. The study highlighted considerations to be addressed in the development of effective and sustainable intergenerational programs. For example, accessing people in the community who are most socially isolated and lonely was identified as a primary challenge. More evidence-based research is needed to support involvement of different cohorts, such as those who are frail, or living with physical or cognitive limitations.

Background Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Methods In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data. Results Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96−1.13; frailty index HR: 1.03, 95% CI 0.97−1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups. Conclusions Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty.

Introduction: Echinocandin antifungal medications including micafungin are being used more commonly in the treatment of invasive fungal infections in both pediatric and adult patients. Micafungin is also a first-line therapeutic option for candidemia and antifungal prophylaxis in a variety of clinical settings. Hypersensitivity reactions have not been well described; however, isolated cases have been reported. No cases of desensitization to echinocandins have been previously described. Case Presentation: In this report, we described a 14-year-old female with high-risk pre-B cell acute lymphoblastic leukemia diagnosed with pulmonary aspergillosis. She developed a hypersensitivity reaction to micafungin, which was deemed first-line therapy for the infection. A rapid intravenous desensitization protocol was successfully completed without reactions. The patient completed the remaining 2 months of therapy without reactions. Conclusion: This report outlines the first report of a successful desensitization to micafungin or any echinocandin. This is a safe method of completing antifungal therapy in a patient with echinocandin hypersensitivity and may be considered for other patients with micafungin hypersensitivities.

BACKGROUND Poor nutritional status is a risk factor for the development of frailty. Likewise, oral health is independently associated with nutrition. The potential association between oral health and frailty in hospitalised elderly adults has, however, not previously been investigated. OBJECTIVE To investigate the relationship between oral health and frailty in hospitalised elderly adults and to identify the predictors of frailty. METHOD A cross-sectional study of 168 geriatric inpatients >65 years old was performed from August to December 2016. Patients of non-English speaking background, with impaired cognition (MMSE

To ascertain the trajectories of mental health among women in Australia assessed in repeat waves from their early 70 s to the end of their lives or their mid 80 s.Secondary analysis of data contributed by the 1921-26 cohort of the Australian Longitudinal Study of Women's Health Waves 1-6. Primary outcome was the 4-item SF-36 Vitality Subscale, which assesses mental health as life satisfaction, social participation, energy and enthusiasm. Structural, individual and intermediary factors were assessed using study-specific and standardised measures. Trajectories were identified using Growth Mixture Modelling and associations with baseline characteristics with Structural Equation Modelling.12,432 women completed Survey One. Three mental health trajectories: stable high (77%); stable low (18.2%) and declining from high to low (4.8%) were identified. Compared to the stable high group, women in the stable low group were significantly less physically active, had more nutritional risks, more recent adverse life events, fewer social interactions and less social support, reported more stress and were more likely to have a serious illness or disability at Survey One. The declining group had similar characteristics to the stable high group, but were significantly more likely to report at baseline that they had experienced recent financial, physical and emotional elder abuse. These interact, but not directly with socioeconomic position and marital status.Mental health among older women is related to social relationships, general health, access to physical activity and healthy nutrition, coincidental adverse life events and experiences of interpersonal violence, in particular elder abuse.

Clinical quality registries are increasingly utilised to monitor and improve healthcare quality. Opt-out consent is recommended to maximise participation and ensure validity of data, however, presents specific considerations when including persons with impaired decision-making abilities. This paper describes the innovative Australian Dementia Network Registry recruitment framework designed to optimise inclusion of people with dementia and mild cognitive impairment.

BackgroundSocial isolation is associated with an increased risk of adverse health outcomes, including functional decline, cognitive decline, and dementia. Intergenerational engagement, i.e. structured or semi structured interactions between non-familial older adults and younger generations is emerging as a tool to reduce social isolation in older adults and to benefit children and adults alike. This has great potential for our communities, however, the strength and breadth of the evidence for this is unclear. We undertook a systematic review to summarise the existing evidence for intergenerational interventions with community dwelling non-familial older adults and children, to identify the gaps and to make recommendations for the next steps.MethodsMedline, Embase and PsychInfo were searched from inception to the 28th Sept 2020. Articles were included if they reported research studies evaluating the use of non-familial intergenerational interaction in community dwelling older adults. PROSPERO registration number CRD42020175927 RESULTS: Twenty articles reporting on 16 studies were included. Although all studies reported positive effects in general, numerical outcomes were not recorded in some cases, and outcomes and assessment tools varied and were administered un-blinded. Caution is needed when making interpretations about the efficacy of intergenerational programmes for improving social, health and cognitive outcomes.DiscussionOverall, there is neither strong evidence for nor against community based intergenerational interventions. The increase in popularity of intergenerational programmes alongside the strong perception of potential benefit underscores the urgent need for evidence-based research.

Care quality has important implications for people with dementia. We examined trends and geographical variation of four clinical quality indicators (CQIs) in Australia. This retrospective cohort study included all people with dementia using Australian government-subsidised aged care in 2008–2016 (n = 373,695). Quality indicator data were derived from linked national aged care, health, and pharmaceutical datasets. Negative binomial regression modelling assessed trends in CQI performance over time (2011–2016) and funnel plots examined geographical variation in performance. The incidence rate of antipsychotic medicine dispensing decreased slightly from 1.17/1000 person-days to 1.07/1000 person-days (adjusted incidence rate ratio (aIRR) = 0.98, 95%CI 0.98–0.99). Cholinesterase inhibitors and memantine dispensing did not change (aIRR = 1.02, 95%CI 1.00–1.04), while exposure to high sedative load increased slightly from 1.39/1000 person-days to 1.44/1000 person-days (aIRR = 1.01, 95%CI 1.00–1.01). Dementia and delirium-related hospitalisations increased slightly from 0.17/1000 person-days to 0.18/1000 person-days (aIRR = 1.02, 95%CI 1.01–1.03). There was marked variation in cholinesterase inhibitor and memantine dispensing by geographical area (0–41%). There has been little change in four indicators of dementia care quality in Australian aged care users over time. Cholinesterase inhibitor and memantine dispensing varied substantially by geographical region. Existing strategies to improve national performance on these indicators appear to be insufficient, despite the significant impact of these indicators on outcomes for people with dementia.

Objective: To describe the prevalence, location and impact of moderate to severe pain experienced on most days in community-dwelling older (≥70 years) adults who were ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial participants. Methods: Cross-sectional ASPREE Longitudinal Study of Older Persons (ALSOP) data were collected from self-reported questionnaires administered to 16,439 ASPREE participants. Results: Of 14,155 respondents, 41% of males ( n = 2651/6475) and 50% of females ( n = 3803/7680) reported experiencing pain on most days. One quarter of respondents reported experiencing pain on most days that was moderate or severe in intensity ( n = 3560/14,155), commonly located in the lower back, knees and upper back. Of those reporting moderate or severe pain, 51% reported taking analgesic medication on most days ( n = 1812/3560), almost one-third also reported regular interference with sleep (29%, n = 1024/3560), walking (35%, n = 1239/3560) and daily activities (41%, n = 1467/3560). Discussion: Lower back, knee or upper back pain is a common accompaniment of ageing.

Background Dementia was identified as a priority area for the development of a Clinical Quality Registry (CQR) in Australia in 2016. The Australian Dementia Network (ADNeT) Registry is being established as part of the ADNeT initiative, with the primary objective of collecting data to monitor and enhance the quality of care and patient outcomes for people diagnosed with either dementia or Mild Cognitive Impairment (MCI). A secondary aim is to facilitate the recruitment of participants into dementia research and trials. This paper describes the Registry protocol. Methods The ADNeT Registry is a prospective CQR of patients newly diagnosed with either dementia or MCI. Eligible patients will be identified initially from memory clinics and individual medical specialists (e.g., geriatricians, psychiatrists and neurologists) involved in the diagnosis of dementia. Participants will be recruited using either an opt-out approach or waiver of consent based on three key determinants (capacity, person responsible, and communication of diagnosis). Data will be collected from four sources: participating sites, registry participants, carers, and linkage with administrative datasets. It is anticipated that the Registry will recruit approximately 10,000 participants by the end of 2023. The ADNeT registry will be developed and implemented to comply with the national operating principles for CQRs and governed by the ADNeT Registry Steering Committee. Discussion The ADNeT Registry will provide important data on current clinical practice in the diagnosis, treatment and care of people with dementia and MCI in Australia as well as long-term outcomes among these people. These data will help to identify variations in clinical practice and patient outcomes and reasons underlying these variations, which in turn, will inform the development of interventions to improve care and outcomes for people with dementia and MCI.

Clinical Quality Registries (CQRs) can improve the quality and safety of care by benchmarking clinical practice,informing policy and service design,feeding information back to providers,and complementing research about the effectiveness of care.

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma – viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2–3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.

BACKGROUND: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking. OBJECTIVE: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people. DESIGN: Prospective cohort study. SETTING: Primary care (Australia and USA). PARTICIPANTS: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100. MEASUREMENTS: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition. RESULTS: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1–2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications. LIMITATIONS: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible. CONCLUSIONS: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-020-06550-2.

Background Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin’s effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults. Methods The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk. Results Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66–1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12). Discussion Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability.

Purpose: To describe the baseline participant characteristics in the ASPREE-AMD study, investigating the effect of aspirin on AMD incidence and progression. Methods: Australian participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, randomized to 100 mg aspirin daily or placebo, had non-mydriatic, digital color fundus images graded according to the Beckman AMD classification. Associations with AMD were determined for baseline characteristics and genetic risk variants. Results: ASPREE-AMD sub-study enrolled 4993 participants with gradable macular images. Median age was 73.4 years (IQR, 71.5, 76.6), 52% were female, 10% had diabetes mellitus, 73% had hypertension, and 44% were former/current smokers. Early, intermediate and late AMD (detected in 20.6%, 16.1%, 1.1%, respectively), significantly associated with age, were also associated with increasing HDL levels: OR = 1.52 (95%CI, 1.26, 1.84), OR = 1.43 (1.17, 1.77) and OR = 1.96 (1.02, 3.76), respectively. Female sex was associated with early [OR = 1.37 (1.16, 1.62)], and intermediate [OR = 1.35 (1.12, 1.63)] AMD, as was previous regular use of aspirin, with OR = 1.46 (1.11, 1.92) and OR = 1.37 (1.01, 1.85), respectively. Current smoking had increased odds for late AMD, OR = 4.02 (1.42, 11.36). Genetic risk variant rs3750846 (ARMS2/HTRA1) was associated with each AMD stage (p

Background A clinical quality registry (CQR) for dementia provides benefits to those living with dementia and their carers by improving the quality and experience of care through benchmarking and monitoring patient outcomes. CQRs use data collected to form clinical quality indicators (CQIs) through which variations in clinical processes and outcomes between different services and jurisdictions can be highlighted. Objective This modified Delphi study aimed to develop CQIs for a pilot Australian CQR for dementia and mild cognitive impairment. These CQIs are based on evidence, patient and caregiver experience, and clinician perspectives across the trajectory of care from diagnosis to end-of-life. Methods An initial list of indicators from existing dementia registries, academic literature, and clinical practice guidelines was synthesized. A working group of clinicians and registry experts further refined these indicators. A panel of experts comprised of a consumer, a carer, clinicians, consumer organization representatives, and academics. The experts participated in three phases of the modified Delphi study: 1) online survey for scoring importance and validity, 2) a one-day face-to-face discussion, and 3) final survey round to assess importance, validity, and feasibility. Results The panel assessed 33 CQIs and confirmed a final set of 18 indicators. The CQIs mapped to the domains of quality of diagnosis, quality of management, access to services and supports, and potentially preventable complications. These CQIs will be tested initially in memory clinics and inform the data collection processes for the Australia Dementia Network Registry (ADNet). Conclusion A dementia CQR is fundamental to ongoing monitoring and development of good quality and consistent care across Australia.

As the novel coronavirus SARS-CoV-2 caused COVID-19 cases in the United States the initial test was developed and performed at the Center for Disease Control (CDC). As the number of cases increased the demand for tests multiplied, leading the CDC to utilize the Emergency Utilization Authorization to allow clinical and commercial laboratories to develop tests to detect the presence of the virus. Many nucleic acid tests based on reverse transcriptase-polymerase chain reaction (RT-PCR) were developed, each with different techniques, specifications and turnaround time. As the illnesses turned into a pandemic, testing became more crucial. The test supply became inadequate to meet the need that it had to be prioritized according to guidance. For surveillance, the need for serologic tests emerged. Here we review the timeline of test development, the turn-around times, the various approved tests and compare them as regards the genes they detect. We concentrate on the point-of-care tests and discuss the basis for new serologic tests. We discuss the testing guidance for prioritization and their application in a hospital setting. As SARS-CoV-2 virus arrived in the USA causing the COVID-19 illness, one of the most talked about issues in the management of the disease and the resulting pandemic has been clinical testing. A unique situation arose of a communicable and highly contagious disease necessitating the rapid diagnosis of patients and the identification of non-symptomatic infected persons. Unfortunately, the USA did not have a Food and Drug Administration (FDA) approved laboratory test for the illness. The FDA ultimately utilized its Emergency Use Authorizations (EUA) on February 4, 2020 to allow for more rapid and widespread development and implementation of in-vitro testing.1 Indeed, companies and organizations utilized the EUA to file applications for new tests based on different methodologies, amounting to 48 applications in the span of 3 months from the beginning of February to the end of April 2020. In addition, multiple other tests were put in place under a separate authorization by a Presidential memorandum in early March allowing laboratories that carry Clinical Laboratory Improvement Amendment (CLIA) certification to put tests in place without an EUA from the FDA. This created an unprecedented situation where the medical community and the public may not be familiar with the various new tests for COVID-19 that are offered to patients and hospitals. The purpose of this review is to provide information, up-to-date as of the date of submission of the manuscript to the journal, on the various tests that have been developed, their scientific basis and their interpretation. We give a real-world example demonstrating the time lag in the return of test results and review testing prioritization guidance since the supply of tests remains below the perceived need.

BACKGROUND Australian guidelines advocate referral to comprehensive memory services for dementia diagnosis, but many patients may be diagnosed elsewhere. AIMS To determine common settings for dementia diagnosis in Australia and to compare patient and carer experience between settings. METHODS Exploratory cross-sectional study of patients with dementia admitted to a Melbourne sub-acute hospital. Patients who had capacity to participate were included; carers were recruited for patients without capacity. Participants completed an interviewer-administered survey which asked them to recall the diagnostic setting, discussions about diagnosis and management (clinical care) and overall experience of diagnosis. Descriptive statistics were applied and open-ended questions were analysed using inductive and deductive coding approaches. RESULTS From 81 eligible participants, 74 consented to participate (one patient, 74 carers). Participants reported dementia diagnosis occurred a median of 24 months before interview, in the following settings: hospitals (31.3%), private specialist clinics (29.7%), memory clinics (14.9%), general practice (13.5%), community health services (9.5%) and residential care (1.4%). Recall of discussions about dementia-modulating medications was higher in participants diagnosed in memory clinics and private specialist clinics (70%) compared to other settings (15%) (P

Background Understanding the long-term health effects of low to moderate alcohol consumption is important for establishing thresholds for minimising the lifetime risk of harm. Recent research has elucidated the dose-response relationship between alcohol and cardiovascular outcomes, showing an increased risk of harm at levels of intake previously thought to be protective. The primary objective of this review was to examine (1) whether there is a dose-response relationship between levels of alcohol consumption and long-term cognitive effects, and (2) what the effects are of different levels of consumption. Methods The review was conducted according to a pre-specified protocol. Eligible studies were those published 2007 onwards that compared cognitive function among people with different levels of alcohol consumption (measured ≥ 6 months prior to first follow-up of cognition). Major cognitive impairment was excluded. Searches were limited to MEDLINE, Embase and PsycINFO (January 2007 to April 2018). Screening, data extraction, and risk of bias assessment (ROBINS-I) were piloted by three authors, then completed by a single author and checked by a second. Analyses were undertaken to identify and characterise dose-response relationships between levels of alcohol consumption and cognition. Certainty of evidence was assessed using GRADE. Results We included 27 cohort studies (from 4786 citations). Eighteen studies examined the effects of alcohol consumption at different levels (risk of bias 16 serious, 2 critical). Ten studies provided data for dose-response analysis. The pooled dose-response relationship showed a maximum standardised mean difference (SMD) indicating slightly better cognition among women with moderate alcohol consumption compared to current non-drinkers (SMD 0.18, 95%CI 0.02 to 0.34, at 14.4 grams/day; 5 studies, very low certainty evidence), and a trivial difference for men (SMD 0.05, 95% CI 0.00 to 0.10, at 19.4 grams/day; 6 studies, very low certainty evidence). Conclusions Major limitations in the design and reporting of included studies made it impossible to discern if the effects of ‘lower’ levels of alcohol intake are due to bias. Further review of the evidence is unlikely to resolve this issue without meta-analysis of individual patient data from cohort studies that address biases in the selection of participants and classification of alcohol consumption.

The influence of the concentration of a commercial photochromic dye, incorporated into as-spun and drawn fibres produced from polyethylene and polypropylene, on their mechanical properties was investigated. As-spun fibres were produced by incorporating a commercial photochromic dye at different concentrations at the extrusion stage of the production process of polypropylene, polyethylene and polyester. The fibres from polypropylene and polyethylene, which showed photochromism when exposed to UV light, were then drawn, and their mechanical properties evaluated and analysed using a factorial experimental design, applying appropriate statistical methods. No further investigation was carried out on the polyester as the dye appeared to degrade at the higher temperatures required for its extrusion, leading to a brown fibre, which was not photochromic. According to the analyses, the most significant parameter influencing the mechanical properties of the as-spun fibres was the polymer type; the effect of the dye concentration was dominated by the significance of the polymer type. The effects of the multi-stage hot-drawing process used to produce the fibres on the mechanical properties of the drawn polypropylene and polyethylene fibres were characterised and statistically modelled. It was found that the dyeing concentration had a negative effect on the tenacity and the modulus of the drawn polypropylene fibres but a positive effect on the tenacity and the modulus of the drawn polyethylene fibres. A dye concentration of 0.2% on mass of polymer had a positive effect on the elongation of the drawn polypropylene and polyethylene fibres, whereas the higher dye concentration of 0.4% had a negative effect on the elongation of both drawn fibres. A new forecasting data source was obtained to optimise the selection of the polymer and the dye concentration and to specify the direction of modification, either increasing or decreasing, the significant process parameters.

ObjectivesThe onset of many illnesses is confounded with age and sex. Increasing age is a risk factor for the development of many illnesses, and sexual dimorphism influences brain anatomy, function, and cognition. Here, we examine frequency-specific connectivity in resting-state networks in a large sample (n = 406) of healthy aged adults.MethodWe quantify frequency-specific connectivity in three resting-state networks known to be implicated in age-related decline: the default mode, dorsal attention, and salience networks, using multiband functional magnetic resonance imaging. Frequency-specific connectivity was quantified in four bands: low (0.015–0.027 Hz), moderately low (0.027–0.073 Hz), moderately high (0.073–0.198 Hz), and high (0.198–0.5 Hz) frequency bands, using mean intensity and spatial extent. Differences in connectivity between the sexes in each of the three networks were examined.ResultsEach network showed the largest intensity and spatial extent at low frequencies and smallest extent at high frequencies. Males showed greater connectivity than females in the salience network. Females showed greater connectivity than males in the default mode network.DiscussionResults in this healthy aged cohort are compatible with those obtained in young samples, suggesting that frequency-specific connectivity, and differences between the sexes, are maintained into older age. Our results indicate that sex should be considered as an influencing factor in studies of resting-state connectivity.

Ingestible sensors are potentially a powerful tool for monitoring human health. Sensors have been developed that can, for example, provide pH and pressure readings or monitor medication, but capsules that can provide key information about the chemical composition of the gut are still not available. Here we report a human pilot trial of an ingestible electronic capsule that can sense oxygen, hydrogen, and carbon dioxide. The capsule uses a combination of thermal conductivity and semiconducting sensors, and their selectivity and sensitivity to different gases is controlled by adjusting the heating elements of the sensors. Gas profiles of the subjects were obtained while modulating gut microbial fermentative activities by altering their intake of dietary fibre. Ultrasound imaging confirmed that the oxygen-equivalent concentration profile could be used as an accurate marker for the location of the capsule. In a crossover study, variations of fibre intake were found to be associated with differing small intestinal and colonic transit times, and gut fermentation. Regional fermentation patterns could be defined via hydrogen gas profiles. Our gas capsule offers an accurate and safe tool for monitoring the effects of diet of individuals, and has the potential to be used as a diagnostic tool for the gut. In a human pilot trial, ingestible electronic capsules, which can sense oxygen, hydrogen, and carbon dioxide gas in the gut, have been shown to be capable of monitoring changes in a person’s diet.

Biomolecular monitoring in the gastrointestinal tract could offer rapid, precise disease detection and management but is impeded by access to the remote and complex environment. Here, we present an ingestible micro-bio-electronic device (IMBED) for in situ biomolecular detection based on environmentally resilient biosensor bacteria and miniaturized luminescence readout electronics that wirelessly communicate with an external device. As a proof of concept, we engineer heme-sensitive probiotic biosensors and demonstrate accurate diagnosis of gastrointestinal bleeding in swine. Additionally, we integrate alternative biosensors to demonstrate modularity and extensibility of the detection platform. IMBEDs enable new opportunities for gastrointestinal biomarker discovery and could transform the management and diagnosis of gastrointestinal disease.

Objective (1) To identify gaps in providers knowledge on opioid medication and dosing, patient-specific characteristics that require alterations in dosing, and patient monitoring and treatment adjustments. (2) To evaluate an educational intervention aimed at minimizing these deficits. Design Observational prospective study. Providers took an anonymous paired pre-and posteducation knowledge assessment before and after participating in a 75-minute educational session. Results before and after the educational session were compared. Setting Surgical providers included nurse practitioners, physician assistants, preinterns, and general surgery residents across 4 quaternary care hospitals in Boston. Participants There were 194 participants and 174 completed both pre- and posteducation knowledge assessments. Results Average scores on the educational assessment increased from 59% before the course to 68% after the session. Posteducation, providers reported increased comfort in prescribing and 95% stated that the curriculum would impact their practice. Conclusions Surgical providers at multiple hospitals have significant gaps in knowledge for optimal prescribing and management of opioid prescriptions. A 75-minute opioid education session increased prescriber knowledge as well as comfort in prescribing. This multicenter study demonstrates how an educational initiative can be implemented broadly and result in decreased knowledge gaps.

Background and Objectives Patient-reported outcome measures (PROMs) captures the patient’s perspective regarding quality of life, daily functioning, symptom severity, and overall health, and how these may be impacted by health care or other interventions. PROMs are used in clinical quality registries (CQRs) for a number of diseases to assess the patient’s perspective of the impact of clinical care on quality-of-life. This scoping review aimed to identify dementia-specific PROMs, determine how the PROMs are being used, and whether they are used within dementia registries. Research Design and Methods Three electronic databases were searched using Medical Subject Heading terms for dementia, quality of life, and patient-reported outcomes. Data were extracted on the PROMs used and the methods and mode of administering the PROM. Results Seven dementia-specific PROMs were identified, however none were used in a dementia registry. All the PROMs were used at the patient level to identify patient needs and health service impacts. Three PROMs were also used at a system level to examine difference in care models. The majority of the PROMs were administered via a researcher or clinician and were predominantly completed by a proxy. Discussion and Implications PROMs provide an opportunity for a patient with dementia to share experiences and perspectives of care. A number of dementia-specific PROMs exist, yet none are used in dementia registries and the majority of studies utilize PROMs via a proxy. The use of PROM for patients with dementia, particularly in the context of dementia registries, requires further exploration and consideration.

PurposeClinical quality registries (CQRs) are being established in many countries to monitor, benchmark, and report on the quality of dementia care over time. Case ascertainment can be challenging given that diagnosis occurs in a variety of settings. The Registry of Senior Australians (ROSA) includes a large cohort of people with dementia from all Australian states and territories identified using routinely collected aged care assessment data. In ROSA, assessment data are linked to information about aged and health service use, medicine dispensing, hospitalisations and the National Death Index. The ROSA dementia cohort was established to capture people for the Australian dementia CQR currently in development who may not be identified elsewhere.ParticipantsThere were 373 695 people with dementia identified in aged care assessments from 2008 to 2016. Cross-sectional analysis from the time of cohort entry (e.g. when first identified with dementia on an aged care assessment) indicates that individuals were 84.1 years old on average, and 63.1% were female. More than 44% were first identified at entry to permanent residential aged care. The cohort recorded more severe cognitive impairment at entry than other international dementia registries.Findings to dateThe cohort has so far been used to demonstrate a declining prevalence of dementia in individuals entering the aged care sector, examine trends in psychotropic medicine prescribing, and to examine the impact of dementia on aged care service use and outcomes.Future plansThe ROSA dementia cohort will be updated periodically and is a powerful resource both on its own and as a contributor to the Australian dementia CQR. Integration of the ROSA dementia cohort with the dementia CQR will ensure that people with dementia using aged care services can benefit from the ongoing monitoring and benchmarking of care that a registry can provide.

Research Aims: This study seeks to understand whether those with dementia experience higher risk of death, using data from the ASPREE (ASPirin in Reducing Events in the Elderly) clinical trial study. Methods: ASPREE was a primary intervention trial of low-dose aspirin among healthy older people. The Australian cohort included 16,703 dementia-free participants aged 70 years and over at enrolment. Participants were triggered for dementia adjudication if cognitive test results were poorer than expected, self-reporting dementia diagnosis or memory problems, or dementia medications were detected. Incidental dementia was adjudicated by an international adjudication committee using the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) criteria and results of a neuropsychological battery and functional measures with medical record substantiation. Statistical analyses used a cox proportional hazards model. Results: As previously reported, 1052 participants (5.5%) died during a median of 4.7 years of follow-up and 964 participants had a dementia trigger, of whom, 575 (60%) were adjucated as having dementia. Preliminary analyses has shown that the mortality rate was higher among participants with a dementia trigger, regardless of dementia adjudication outcome, than those without (15% vs 5%, Χ2 = 205, p