Intranasal insulin for treatment of delirium in older hospitalised patients: Study protocol for a randomised controlled trial

Introduction Delirium is one of the most common conditions diagnosed in hospitalised older people and is associated with numerous adverse outcomes, yet there are no proven pharmacological treatments. Recent research has identified cerebral glucose hypometabolism as a pathophysiological mechanism offering a therapeutic target in delirium. Insulin, delivered via the intranasal route, acts directly on the central nervous system and has been shown to enhance cerebral metabolism and improve cognition in patients with mild cognitive impairment and dementia. This trial will determine whether intranasal insulin can reduce the duration of delirium in older hospitalised patients. Methods and analysis This is a prospective randomised, placebo-controlled, double-blind study with 6 months follow-up. One hundred patients aged 65 years or older presenting to hospital with delirium admitted under geriatric medicine will be recruited. Participants will be randomised to intranasal insulin detemir or placebo administered twice daily until delirium resolves, defined as Confusion Assessment Method (CAM) negative for 2 days, or discharge from hospital. The primary outcome measure will be duration of delirium using the CAM. Secondary outcome measures will include length of hospital stay, severity of delirium, adherence to treatment, hospital complications, new admission to nursing home, mortality, use of antipsychotic medications during hospital stay and cognitive and physical function at 6 months postdischarge. Ethics and dissemination This trial has been approved by the South Eastern Sydney Human Research and Ethics Committee. Dissemination plans include submission to a peer-reviewed journal for publication and presentation at scientific conferences. Trial registration number ACTRN12618000318280

Type 2 diabetes, socioeconomic status and life expectancy in Scotland (2012-2014):a population-based observational study

Aims/hypothesis: The aim of this study was to assess the role of socioeconomic status (SES) in the associations between type 2 diabetes and life expectancy in a complete national population. Methods: An observational population-based cohort study was performed using the Scottish Care Information – Diabetes database. Age-specific life expectancy (stratified by SES) was calculated for all individuals with type 2 diabetes in the age range 40–89 during the period 2012–2014, and for the remaining population of Scotland aged 40–89 without type 2 diabetes. Differences in life expectancy between the two groups were calculated. Results: Results were based on 272,597 individuals with type 2 diabetes and 2.75 million people without type 2 diabetes (total for 2013, the middle calendar year of the study period). With the exception of deprived men aged 80–89, life expectancy in people with type 2 diabetes was significantly reduced (relative to the type 2 diabetes-free population) at all ages and levels of SES. Differences in life expectancy ranged from −5.5 years (95% CI −6.2, −4.8) for women aged 40–44 in the second most-deprived quintile of SES, to 0.1 years (95% CI −0.2, 0.4) for men aged 85–89 in the most-deprived quintile of SES. Observed life-expectancy deficits in those with type 2 diabetes were generally greater in women than in men. Conclusions/interpretation: Type 2 diabetes is associated with reduced life expectancy at almost all ages and levels of SES. Elimination of life-expectancy deficits in individuals with type 2 diabetes will require prevention and management strategies targeted at all social strata (not just deprived groups)

Regional genioglossus reflex responses to negative pressure pulses in people with obstructive sleep apnea

Tongue and upper airway dilator muscle movement patterns during quiet breathing vary in people with obstructive sleep apnea (OSA). Many patients have inadequate or counterproductive responses to inspiratory negative airway pressure that likely contributes to their OSA. This may be due, at least in part, to inadequate or nonhomogeneous reflex drive to different regions of the largest upper airway dilator, genioglossus. To investigate potential regional heterogeneity of genioglossus reflex responses in OSA, brief suction pulses were applied via a nasal breathing mask and an electromyogram (EMG) was recorded in four regions (anterior oblique, anterior horizontal, posterior oblique, and posterior horizontal) using intramuscular fine wire electrodes in 15 people with OSA. Genioglossus short-latency reflex excitation amplitude had regional heterogeneity (horizontal vs. oblique regions) when expressed in absolute units but homogeneity when normalized as a percentage of the immediate (100 ms) prestimulus EMG. Regional variability in reflex morphology (excitation and inhibition) was present in one-third of the participants. The minimum cross-sectional area (CSA) of the pharyngeal airway was quantified using MRI and may be related to the amplitude of the short-latency reflex response to negative pressure as we found that people with a smaller CSA tended to have a greater reflex amplitude (e.g., horizontal region r2 = 0.41, P = 0.01). These findings highlight the complexity of genioglossus reflex control, the potential for regional heterogeneity, and the functional importance of upper airway anatomy in mediating genioglossus reflex responses to rapid changes in negative pressure in OSA

COVID-19, alcohol consumption and stockpiling practises in midlife women: repeat surveys during lockdown in Australia and the United Kingdom

Introduction: This project examined the impact of COVID-19 and associated restrictions on alcohol practises (consumption and stockpiling), and perceptions of health risk among women in midlife (those aged 45–64 years). Methods: We collected online survey data from 2,437 midlife women in the United Kingdom (UK) and Australia in May 2020, recruited using a commercial panel, in the early days of mandated COVID-19 related restrictions in both countries. Participants were surveyed again (N = 1,377) in July 2020, at a time when COVID-19 restrictions were beginning to ease. The surveys included the Alcohol Use Disorder Identification Test—Consumption (AUDIT-C) and questions alcohol stockpiling. Analysis involved a range of univariate and multivariate techniques examining the impact of demographic variables and negative affect on consumption and acquisition outcomes. Results: In both surveys (May and July), UK women scored higher than Australian women on the AUDIT-C, and residence in the UK was found to independently predict stockpiling of alcohol (RR: 1.51; 95% CI: 1.20, 1.91). Developing depression between surveys (RR: 1.53; 95% CI: 1.14, 2.04) and reporting pessimism (RR: 1.42; 95% CI: 1.11, 1.81), and fear/anxiety (RR: 1.33; 95% CI: 1.05, 1.70) at the beginning of the study period also predicted stockpiling by the end of the lockdown. Having a tertiary education was protective for alcohol stockpiling at each time point (RR: 0.69; 95% CI: 0.54, 0.87). Conclusions: COVID-19 was associated with increases in risky alcohol practises that were predicted by negative emotional responses to the pandemic. Anxiety, pessimism and depression predicted stockpiling behaviour in UK and Australian women despite the many demographic and contextual differences between the two cohorts. Given our findings and the findings of others that mental health issues developed or were exacerbated during lockdown and may continue long after that time, urgent action is required to address a potential future pandemic of alcohol-related harms.Emma R. Miller, Ian N. Olver, Carlene J. Wilson, Belinda Lunnay, Samantha B. Meyer, Kristen Foley ... et al

Social class and changes in Australian women's affect and alcohol consumption during COVID-19

Introduction: Before the pandemic, mid-life women in Australia were among the “heaviest” female alcohol consumers, giving rise to myriad preventable health risks. This paper uses an innovative model of social class within a sample of Australian women to describe changes in affective states and alcohol consumption patterns across two time points during COVID-19. Methods: Survey data were collected from Australian mid-life women (45–64 years) at two time points during COVID-19—May 2020 (N = 1,218) and July 2020 (N = 799). We used a multi-dimensional model for measuring social class across three domains—economic capital (income, property and assets), social capital (social contacts and occupational prestige of those known socially), and cultural capital (level of participation in various cultural activities). Latent class analysis allowed comparisons across social classes to changes in affective states and alcohol consumption patterns reported at the two time points using alcohol consumption patterns as measured by the Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its component items. Results: Seven social classes were constructed, characterized by variations in access to capital. Affective states during COVID-19 differed according to social class. Comparing between the survey time points, feeling fearful/anxious was higher in those with high economic and cultural capital and moderate social capital (“emerging affluent”). Increased depression was most prominent in the class characterized by the highest volumes of all forms of capital (“established affluent”). The social class characterized by the least capital (“working class”) reported increased prevalence of uncertainty, but less so for feeling fearful or anxious, or depressed. Women's alcohol consumption patterns changed across time during the pandemic. The “new middle” class—a group characterized by high social capital (but contacts with low prestige) and minimal economic capital—had increased AUDIT-C scores. Conclusion: Our data shows the pandemic impacted women's negative affective states, but not in uniform ways according to class. It may explain increases in alcohol consumption among women in the emerging affluent group who experienced increased feelings or fear and anxiety during the pandemic. This nuanced understanding of the vulnerabilities of sub-groups of women, in respect to negative affect and alcohol consumption can inform future pandemic policy responses designed to improve mental health and reduce the problematic use of alcohol. Designing pandemic responses segmented for specific audiences is also aided by our multi-dimensional analysis of social class, which uncovers intricate differences in affective states amongst sub-groups of mid-life women.Belinda Lunnay, Barbara Toson, Carlene Wilson, Emma R. Miller, Samantha Beth Meyer, Ian N. Olver, Kristen Foley, Jessica A. Thomas and Paul Russell War

Exergame and cognitive training for preventing falls in community-dwelling older people: a randomized controlled trial

Exergame training, in which video games are used to promote exercise, can be tailored to address cognitive and physical risk factors for falls and is a promising method for fall prevention in older people. Here, we performed a randomized clinical trial using the smart±step gaming system to examine the effectiveness of two home-based computer game interventions, seated cognitive training and step exergame training, for fall prevention in community-dwelling older people, as compared with a minimal-intervention control group. Participants aged 65 years or older (n = 769, 71% female) living independently in the community were randomized to one of three arms: (1) cognitive training using a computerized touchpad while seated, (2) exergame step training on a computerized mat or (3) control (provided with an education booklet on healthy ageing and fall prevention). The rate of falls reported monthly over 12 months—the primary outcome of the trial—was significantly reduced in the exergame training group compared with the control group (incidence rate ratio = 0.74, 95% confidence interval = 0.56–0.98), but was not statistically different between the cognitive training and control groups (incidence rate ratio = 0.86, 95% confidence interval = 0.65–1.12). No beneficial effects of the interventions were found for secondary outcomes of physical and cognitive function, and no serious intervention-related adverse events were reported. The results of this trial support the use of exergame step training for preventing falls in community-dwelling older people. As this intervention can be conducted at home and requires only minimal equipment, it has the potential for scalability as a public health intervention to address the increasing problem of falls and fall-related injuries. Australian and New Zealand Clinical Trial Registry identifier: ACTRN12616001325493

Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study

Published: 24 May 2023. Corrected by: Corrigendum to: Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study (Nat Sci Sleep. 2023, 15, 389–406.) In vol. 15 (2023), pp. 433-434. The authors advise that the funding section on page 404 is incorrect.Purpose: Prospective studies examining associations between baseline sleep microarchitecture and future cognitive function recruited from small samples with predominantly short follow-up. This study examined sleep microarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8 years in community-dwelling men. Patients and Methods: Florey Adelaide Male Ageing Study participants (n=477) underwent home-based polysomnography (2010– 2011), with 157 completing baseline (2007– 2010) and follow-up (2018– 2019) cognitive assessments (trail-making tests A [TMT-A] and B [TMT-B] and the standardized mini-mental state examination [SMMSE]). Whole-night F4-M1 sleep EEG recordings were processed following artifact exclusion, and quantitative EEG characteristics were obtained using validated algorithms. Associations between baseline sleep microarchitecture and future cognitive function (visual attention, processing speed, and executive function) were examined using linear regression models adjusted for baseline obstructive sleep apnoea, other risk factors, and cognition. Results: The final sample included men aged (mean [SD]) 58.9 (8.9) years at baseline, overweight (BMI 28.5 [4.2] kg/m2), and well educated (75.2% ≥Bachelor, Certificate, or Trade), with majorly normal baseline cognition. Median (IQR) follow-up was 8.3 (7.9, 8.6) years. In adjusted analyses, NREM and REM sleep EEG spectral power was not associated with TMT-A, TMT-B, or SMMSE performance (all p> 0.05). A significant association of higher N3 sleep fast spindle density with worse TMT-B performance (B=1.06, 95% CI [0.13, 2.00], p=0.026) did not persist following adjustment for baseline TMT-B performance. Conclusion: In this sample of community-dwelling men, sleep microarchitecture was not independently associated with visual attention, processing speed, or executive function after 8 years.Jesse L Parker, Andrew Vakulin, Yohannes Adama Melaku, Gary A Wittert, Sean A Martin, Angela L D, Rozario, Peter G Catcheside, Bastien Lechat, Barbara Toson, Alison J Teare, Sarah L Appleton, Robert J Adam

Associations of baseline obstructive sleep apnea and sleep macroarchitecture with cognitive function after 8 years in middle‐aged and older men from a community‐based cohort study

OnlinePublPrevious prospective studies examining associations of obstructive sleep apnea and sleep macroarchitecture with future cognitive function recruited older participants, many demonstrating baseline cognitive impairment. This study examined obstructive sleep apnea and sleep macroarchitecture predictors of visual attention, processing speed, and executive function after 8 years among younger community-dwelling men. Florey Adelaide Male Ageing Study participants (n = 477) underwent homebased polysomnography, with 157 completing Trail-Making Tests A and B and the Mini-Mental State Examination. Associations of obstructive sleep apnea (apnea– hypopnea index, oxygen desaturation index, and hypoxic burden index) and sleep macroarchitecture (sleep stage percentages and total sleep time) parameters with future cognitive function were examined using regression models adjusted for baseline demographic, biomedical, and behavioural factors, and cognitive task performance. The mean (standard deviation) age of the men at baseline was 58.9 (8.9) years, with severe obstructive sleep apnea (apnea–hypopnea index ≥30 events/h) in 9.6%. The median (interquartile range) follow-up was 8.3 (7.9–8.6) years. A minority of men (14.6%) were cognitively impaired at baseline (Mini-Mental State Examination score <28/30). A higher percentage of light sleep was associated with better TrailMaking Test A performance (B = 0.04, 95% confidence interval [CI] 0.06, 0.01; p = 0.003), whereas higher mean oxygen saturation was associated with worse performance (B = 0.11, 95% CI 0.02, 0.19; p = 0.012). While obstructive sleep apnea and sleep macroarchitecture might predict cognitive decline, future studies should consider arousal events and non-routine hypoxaemia measures, which may show associations with cognitive decline.Jesse L. Parker, Andrew Vakulin, Ganesh Naik, Yohannes Adama Melaku, David Stevens, Gary A. Wittert, Sean A. Martin, Peter G. Catcheside, Barbara Toson, Sarah L. Appleton, Robert J. Adam

Do sensorimotor cortex activity, an individual's capacity for neuroplasticity, and psychological features during an episode of acute low back pain predict outcome at 6 months: a protocol for an Australian, multisite prospective, longitudinal cohort study

INTRODUCTION:Low back pain (LBP) is the leading cause of disability worldwide, with prevalence doubling in the past 14 years. To date, prognostic screening tools display poor discrimination and offer no net benefit of screening over and above a 'treat all' approach. Characteristics of the primary sensory (S1) and motor (M1) cortices may predict the development of chronic LBP, yet the prognostic potential of these variables remains unknown. The Understanding persistent Pain Where it ResiDes (UPWaRD) study aims to determine whether sensorimotor cortex activity, an individual's capacity for plasticity and psychosocial factors in the acute stage of pain, predict LBP outcome at 6 months. This paper describes the methods and analysis plan for the development of the prediction model. METHODS AND ANALYSIS:The study uses a multicentre prospective longitudinal cohort design with 6-month follow-up. 120 participants, aged 18 years or older, experiencing an acute episode of LBP (less than 6 weeks duration) will be included. Primary outcomes are pain and disability. ETHICS AND DISSEMINATION:Ethical approval has been obtained from Western Sydney University Human Research Ethics Committee (H10465) and from Neuroscience Research Australia (SSA: 16/002). Dissemination will occur through presentations at national and international conferences and publications in international peer-reviewed journals. TRIAL REGISTRATION NUMBER:ACTRN12619000002189; Pre-results.Luke C Jenkins, Wei-Ju Chang, Valentina Buscemi, Matthew Liston, Barbara Toson, Michael Nicholas, Thomas Graven-Nielsen, Michael Ridding, Paul W Hodges, James H McAuley, Siobhan M Schabru

Establishing the acute physiological and sleep disruption characteristics of wind farm versus road traffic noise disturbances in sleep: a randomized controlled trial protocol

Advance access publication 6 September 2023Study Objectives: Despite the global expansion of wind farms, effects of wind farm noise (WFN) on sleep remain poorly understood. This protocol details a randomized controlled trial designed to compare the sleep disruption characteristics of WFN versus road traffic noise (RTN). Methods: This study was a prospective, seven night within-subjects randomized controlled in-laboratory polysomnography-based trial. Four groups of adults were recruited from; 15 s events) from sleep by each noise type with acute (20-s) and more sustained (3-min) noise exposures. Secondary analyses will compare dose–response effects of sound pressure level and noise type on EEG K-complex probabilities and quantitative EEG measures, and cardiovascular activation responses. Group effects, self-reported noise sensitivity, and wake versus sleep noise exposure effects will also be examined. Conclusions: This study will help to clarify if wind farm noise has different sleep disruption characteristics compared to road traffic noise.Gorica Micic, Branko Zajamsek, Bastien Lechat, Kristy Hansen, Hannah Scott, Barbara Toson, Tessa Liebich, Claire Dunbar, Duc Phuc Nguyen, Felix Decup, Andrew Vakulin, Nicole Lovato, Leon Lack, Colin Hansen, Dorothy Bruck, Ching Li Chai-Coetzer, Jeremy Mercer, Con Doolan and Peter Catchesid