Low-Dose Morphine Does Not Cause Sleepiness in COPD: A Secondary Analysis of a Randomized Trial.

RATIONALE: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality and daytime function have not been rigorously investigated. OBJECTIVES: Determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. METHODS: Pre-specified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained -release morphine versus placebo over four weeks commencing at 8mg or 16mg/day with blinded up-titration over two weeks to a maximum of 32mg/day. Primary outcomes for these analyses were week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) responses on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire (LSEQ) scores (end of weeks 1 and 4), KSS and ESS beyond week-1 and associations between breathlessness, morphine, and questionnaire scores. MEASUREMENTS AND MAIN RESULTS: 156 people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (∆ESS [95%CI] versus placebo: 8mg group: -0.59 [-1.99, 0.81], p=0.41; 16mg group: -0.72 [-2.33, 0.9], p=0.38; ∆KSS versus placebo: 8mg group: 0.11 [-0.7, 0.9], p=0.78; 16mg group: -0.41 [-1.31, 0.49], p=0.37). This neutral effect persisted at later timepoints. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also had improvement in LSEQ domain scores including perceived sleep quality and daytime function. CONCLUSIONS: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

Latent profiles of fatigue in inflammatory bowel disease.

INTRODUCTION: Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis. METHODS: An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn's Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated. RESULTS: In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32-52 years), and the majority had Crohn's disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile. CONCLUSION: Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

A Multi-Season Randomised Controlled Trial of Advax-Adjuvanted Seasonal Influenza Vaccine in Participants with Chronic Disease or Older Age.

BACKGROUND: The aim of this study was to determine the safety and immunogenicity of trivalent inactivated influenza vaccine (TIV) alone or formulated with Advax™ delta inulin adjuvant in those of older age (> 60 years) or with chronic disease. METHODS: Over four consecutive years from 2008-2011, adult participants with chronic disease or over 60 years were recruited into a randomised controlled study to assess the safety, tolerability and immunogenicity of Advax-adjuvanted versus standard TIV. The per protocol (PP) population with at least one post-baseline measurement of influenza antibodies comprised 1297 participants: 447 in the TIV, and 850 in the Advax-adjuvanted TIV, groups. RESULTS: No safety issues were identified. Variables negatively affecting vaccine responses included obesity and diabetes mellitus. Advax adjuvant had a positive impact on anti-influenza IgM responses and on H3N2 and B strain seropositivity as assessed by hemagglutination inhibition. CONCLUSIONS: Advax-adjuvanted TIV was safe and well tolerated in individuals with chronic disease. There is an ongoing need for research into improved influenza vaccines for high-risk populations. Australia New Zealand Clinical Trial Registry: ACTRN 12608000364370.

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.

Previous 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 home-based 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 Trail-Making 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.

Linking health service utilisation and mortality data-unravelling what happens after fall-related paramedic care.

BACKGROUND: A randomised controlled trial implemented and evaluated a new model of care for non-transported older fallers to prevent future falls and unplanned health service use. This current study uses linked data to evaluate the effects of the intervention beyond the initial 12-month study period. METHOD: Study data from an established cohort of 221 adults were linked to administrative data from NSW Ambulance, Emergency Department Data Collection, Admitted Patient Data Collection and Registry of Births, Deaths and Marriages evaluating health service use at 12, 24 and 36 months following randomisation including time to event (health service utilisation) and mortality. Negative binomial and Cox's proportional hazard regression were performed to capture the impact of the study between groups and adherence status. RESULTS: At 36 months follow-up, 89% of participants called an ambulance, 87% attended the Emergency Department and 91% were admitted to hospital. There were no significant differences in all-cause health service utilisation between the control and intervention group (IG) at 12, 24 and 36 months follow-up. Fall-related health service use was significantly higher within the IG at 12 (IRR:1.40 (95%CI:1.01-1.94) and 24 months (IRR:1.43 (95%CI:1.05-1.95)). Medication use, impaired balance and previous falls were associated with subsequent health service use. Over 40% of participants died by the follow-up period with risk of death lower in the IG at 36 months (HR:0.64, 95%CI:0.45-0.91). CONCLUSION: Non-transported fallers have a high risk of future health service use for fall and other medical-related reasons. Interventions which address this risk need to be further explored.

Does identifying frailty from ICD-10 coded data on hospital admission improve prediction of adverse outcomes in older surgical patients? A population-based study.

BACKGROUND: frailty is a major contributor to poor health outcomes in older people, separate from age, sex and comorbidities. This population-based validation study evaluated the performance of the International Classification of Diseases, 10th revision, coded Hospital Frailty Risk Score (HFRS) in the prediction of adverse outcomes in an older surgical population and compared its performance against the commonly used Charlson Comorbidity Index (CCI). METHODS: hospitalisation and death data for all individuals aged ≥50 admitted for surgery to New South Wales hospitals (2013-17) were linked. HFRS and CCI scores were calculated using both 2- and 5-year lookback periods. To determine the influence of individual explanatory variables, several logistic regression models were fitted for each outcome of interest (30-day mortality, prolonged length of stay (LOS) and 28-day readmission). Area under the receiving operator curve (AUC) and Akaike information criterion (AIC) were assessed. RESULTS: of the 487,197 patients, 6.8% were classified as high HFRS, and 18.3% as high CCI. Although all models performed better than base model (age and sex) for prediction of 30-day mortality, there was little difference between CCI and HFRS in model discrimination (AUC 0.76 versus 0.75), although CCI provided better model fit (AIC 79,020 versus 79,910). All models had poor ability to predict prolonged LOS (AUC range 0.62-0.63) or readmission (AUC range 0.62-0.65). Using a 5-year lookback period did not improve model discrimination over the 2-year period. CONCLUSIONS: adjusting for HFRS did not improve prediction of 30-mortality over that achieved by the CCI. Neither HFRS nor CCI were useful for predicting prolonged LOS or 28-day unplanned readmission.

Respiratory cerebrospinal fluid flow is driven by the thoracic and lumbar spinal pressures.

KEY POINTS: Respiration plays a key role in the circulation of cerebrospinal fluid (CSF) around the central nervous system. During inspiration increased venous return from the cranium is believed to draw CSF rostrally. However, this mechanism does not explain why CSF has also been observed to move caudally during inspiration. We show that during inspiration decreased intrathoracic pressure draws venous blood from the cranium and lumbar spine towards the thorax. We also show that the abdominal pressure was associated with rostral CSF displacement. However, a caudal shift of cervical CSF was seen with low abdominal pressure and comparably negative intrathoracic pressures. These results suggest that the effects of epidural blood flow within the spinal canal need to be considered, as well as the cranial blood volume balance, to understand respiratory-related CSF flow. These results may prove useful for the treatment of CSF obstructive pathology and understanding the behaviour of intrathecal drug injections. ABSTRACT: It is accepted that during inspiration, cerebrospinal fluid (CSF) flows rostrally to compensate for decreased cranial blood volume, caused by venous drainage due to negative intrathoracic pressure. However, this mechanism does not explain observations of caudal CSF displacement during inspiration. Determining the drivers of respiratory CSF flow is crucial for understanding the pathophysiology of CSF flow disorders. To quantify the influence of respiration on CSF flow, real-time phase-contrast magnetic resonance imaging (MRI) was used to record CSF and blood flow, while healthy subjects (5:5 M:F, 25-50 years) performed either a brief expiratory or inspiratory effort between breaths. Transverse images were taken perpendicular to the spinal canal in the middle of the C3 and L2 vertebrae. The same manoeuvres were then performed after a nasogastric pressure catheter was used to measure the intrathoracic and abdominal pressures. During expiratory-type manoeuvres that elevated abdominal and intrathoracic pressures, epidural blood flow into the spinal canal increased and CSF was displaced rostrally. With inspiratory manoeuvres, the negative intrathoracic pressure drew venous blood from C3 and L2 towards the thoracic spinal canal, and cervical CSF was displaced both rostrally and caudally, despite the increased venous drainage. Regression analysis showed that rostral displacement of CSF at both C3 (adjusted R2  = 0.53; P < 0.001) and L2 (adjusted R2  = 0.38; P < 0.001) were associated with the abdominal pressure. However, with low abdominal pressure and comparably negative intrathoracic pressure, cervical CSF flowed caudally. These findings suggest that changes in both the cranial and spinal pressures need to be considered to understand respiratory CSF flow.

The role of cognitive function and physical activity in physical decline in older adults across the cognitive spectrum.

OBJECTIVES: The aim of this study was to investigate physical decline over 1-year in a cohort of older people across the cognitive spectrum. METHODS: Physical function was assessed using the Physiological Profile Assessment (PPA) in 593 participants (cognitively normal [CN]: n = 342, mild cognitive impairment [MCI]: n = 77, dementia: n = 174) at baseline and in 490 participants available for reassessment 1-year later. Neuropsychological performance and physical activity (PA) were assessed at baseline. RESULTS: Median baseline PPA scores for CN, MCI and dementia groups were 0.41 (IQR = -0.09-1.02), 0.66 (IQR = -0.06-1.15) and 2.37 (IQR = 0.93-3.78) respectively. All baseline neuropsychological domains and PA were significantly associated with baseline PPA. There were significant interaction terms (Time × Cognitive Group, Global Cognition, Processing Speed, Executive Function and PA) in the models investigating PPA decline. In multivariate analysis the Time × Executive Function and PA interaction terms were significant, indicating that participants with poorer baseline executive function and reduced PA demonstrated greater physical decline when compared to individuals with better executive function and PA respectively. DISCUSSION: Having MCI or dementia is associated with greater physical decline compared to CN older people. Physical inactivity and executive dysfunction were associated with physical decline in this sample, which included participants with MCI and dementia. Both factors influencing physical decline are potentially amenable to interventions e.g. exercise.

Effects of low-dose morphine on perceived sleep quality in patients with refractory breathlessness: A hypothesis generating study.

BACKGROUND AND OBJECTIVE: The management of chronic refractory breathlessness is one of the indications for regular low-dose (≤30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low-dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality. METHODS: This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male; 33 with COPD) aged 76 ± 0.9 years who completed a double-blind, randomized, placebo-controlled, cross-over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8-day trial. RESULTS: Perceived sleep disruption due to breathlessness over the 4-day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported 'very good' or 'quite good' sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34-0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039). CONCLUSION: Four days of low-dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low-dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality.

Orthogeriatric services associated with lower 30-day mortality for older patients who undergo surgery for hip fracture.

OBJECTIVE: To examine the impact of orthogeriatric services on 30-day mortality and length of stay (LOS) for hip fracture patients undergoing surgery in public hospitals in New South Wales. DESIGN, SETTING AND PATIENTS: A retrospective analysis of patients aged 65 years and older who had a fractured hip and received surgical intervention between 1 July 2009 and 30 June 2011 at one of the 37 NSW public hospitals operating on hip fracture patients. MAIN OUTCOME MEASURES: 30-day mortality and LOS. RESULTS: During the study period, there were 9601 hip fracture cases for which surgery was done. Mean age, sex and comorbidity distribution were similar for hip fracture patients treated in hospitals with an orthogeriatric service compared with those treated in hospitals without an orthogeriatric service. There were 706 deaths within 30 days of hip fracture surgery, and the overall unadjusted 30-day mortality rate was 7.4%. The median adjusted 30-day mortality rate for hospitals with an orthogeriatric service was significantly lower than that for hospitals without an orthogeriatric service (6.2% v 8.4%; P < 0.002). Median total LOS was longer at hospitals with an orthogeriatric service compared with hospitals that did not have an orthogeriatric service (26 days v 22 days; P < 0.001). CONCLUSIONS: The presence of an orthogeriatric service was associated with a reduction in 30-day mortality but a longer LOS. More research is required to understand the key aspects of care that determine health outcomes. The recently launched Australian and New Zealand Hip Fracture Registry will provide data that will enable improvements in care.

Predictors of nontransport of older fallers who receive ambulance care.

OBJECTIVES: To identify patient, clinical, and operational factors associated with nontransport of older people who have fallen and received ambulance care; and to develop a nontransport prediction tool that could be utilized during the dispatch process to rationalize allocation of emergency ambulance resources. METHODS: The study was a planned subanalysis using data collected during a prospective observational cohort study of nonconsecutive emergency responses to older people aged 65 years or more who had fallen between October 1, 2010 and June 30, 2011. The data consisted of routinely collected ambulance dispatch and clinical records, combined with prospectively collected fall-specific information. Missing data were managed using multiple imputation. Multivariate logistic regression modeling was undertaken to identify predictors of nontransport. Results are described for original and imputated data sets, presented as odds ratios (OR) with 95%CI (confidence interval). Receiver operating curve (ROC) statistics were generated, with model discrimination determined by the area under the curve (AUC). RESULTS: There were 1,484 cases eligible for this subanalysis of which 419 (28.2%) were recorded as nontransport. Multivariate regression including dispatch and clinical variables identified a 6-item final model. Younger age group, nonurgent response priority, and presence of a personal alarm were predictors of nontransport, along with clinical variables, including normal vital signs, absence of injury, and unchanged functional status post-fall. The AUC was 0.88 (95% CI 0.86-0.90; p < 0.0001) (imputed data AUC 0.86 (95% CI 0.84-0.88)). Multivariate modeling of dispatch variables only identified a 3-item final model, which included response nonurgent response priority, younger age, and the presence of a personal alarm. The AUC was 0.68 (95% CI 0.64-0.71; p < 0.0001) (imputed data AUC 0.69 (95% CI 0.66-0.72)). CONCLUSION: In this population of confirmed older fallers attended to by paramedics, determination of the prehospital transport outcome is greatly influenced by on-scene findings resulting from paramedic assessment. The presence of new pain, abnormal physiology, and altered function post-fall were strongly associated with increased odds of transport. Conversely the presence of a personal alarm and allocation of a nonurgent dispatch priority increased the odds of nontransport. Accurate discrimination between older fallers who were and were not transported using dispatch data only was not possible.

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 .

A circadian-informed lighting intervention accelerates circadian adjustment to a night work schedule in a submarine lighting environment.

STUDY OBJECTIVE: Night work has detrimental impacts on sleep and performance, primarily due to misalignment between sleep-wake schedules and underlying circadian rhythms. This study tested whether circadian-informed lighting accelerated circadian phase delay, and thus adjustment to night work, compared to blue-depleted standard lighting under simulated submariner work conditions. METHODS: Nineteen healthy sleepers (12 males; mean±SD aged 29 ±10 y) participated in two separate 8-day visits approximately one month apart to receive, in random order, circadian-informed lighting (blue-enriched and dim, blue-depleted lighting at specific times) and standard lighting (dim, blue-depleted lighting). After an adaptation night (day 1), salivary dim light melatonin onset (DLMO) assessment was undertaken from 18:00-02:00 on days 2-3. During days 3-7, participants completed simulated night work from 00:00-08:00 and a sleep period from 10:00-19:00. Post-condition DLMO assessment occurred from 21:00-13:00 on days 7-8. Ingestible capsules continuously sampled temperature to estimate daily core body temperature minimum (Tmin) time. Tmin and DLMO circadian delays were compared between conditions using mixed effects models. RESULTS: There were significant condition-by-day interactions in Tmin and DLMO delays (both p<0.001). After four simulated night shifts, circadian-informed lighting produced a mean [95%CI] 4.3 [3.3 to 5.4] h greater delay in Tmin timing and a 4.2 [3 to 5.6] h greater delay in DLMO timing compared to standard lighting. CONCLUSIONS: Circadian-informed lighting accelerates adjustment to shiftwork in a simulated submariner work environment. Circadian lighting interventions warrant consideration in any dimly lit and blue-depleted work environments where circadian adjustment is relevant to help enhance human performance, safety, and health.

Increased distance or time from a major trauma centre in South Australia is not associated with worse outcomes after moderate to severe traumatic brain injury.

OBJECTIVE: Considerations in traumatic brain injury (TBI) management include time to critical interventions and neurosurgical care, which can be influenced by the geographical location of injury. In Australia, these distances can be vast with varying degrees of first-responder experience. The present study aimed to evaluate the association that distance and/or time to a major trauma centre (MTC) had on patient outcomes with moderate to severe TBI. METHODS: A retrospective cohort study was conducted using data from the Royal Adelaide Hospital's (RAH) Trauma Registry over a 3-year period (1 January 2018 to 31 December 2020). All patients with a moderate to severe TBI (Glasgow Coma Scale [GCS] ≤13 and abbreviated injury score head of ≥2) were included. The association of distance and time to the RAH and patient outcomes were compared by calculating the odds ratio utilising a logistic regression model. RESULTS: A total of 378 patients were identified; of these, 226 met inclusion criteria and comprised our study cohort. Most patients were male (79%), injured in a major city (55%), with median age of 38 years old and median injury severity score (ISS) of 25. After controlling for age, ISS, ED GCS on arrival and pre-MTC intubation, increasing distance or time from injury site to the RAH was not shown to be associated with mortality or discharge destination in any of the models investigated. CONCLUSION: Our analysis revealed that increasing distance or time from injury site to a MTC for patients with moderate to severe TBI was not significantly associated with adverse patient outcomes.

An exploration of healthcare use in older people waiting for and receiving Australian community-based aged care services.

AIM: Home care packages (HCPs) facilitate older individuals to remain at home, with longer HCP wait times associated with increased mortality risk. We analyze healthcare cost data pre- and post-HCP access to inform hypotheses around the effects of healthcare use and mortality risk. METHODS: Regression models were used to assess the impact of delayed HCP access on healthcare costs and to compare costs whilst waiting and in the 6- and 12 month periods post-HCP access for 16 629 older adults. RESULTS: Average wait time for a HCP was 89.7 days (SD = 125.6) during the study period. Wait-time length had no impact on any healthcare cost category or time period. However, total per day healthcare costs were higher in the 6 and 12 months post-receipt of a HCP (AU$61.5, AU$63, respectively) compared with those in the time waiting for a HCP (AU$48.1). Inpatient care accounted for a higher proportion of total healthcare costs post-HCP (AU$45.1, AU$46.3, respectively) compared with in the wait time (AU$30.6), whilst spending on medical services and pharmaceuticals reduced slightly in the 6 month (AU$7.1, AU$6.3) and 12 month (AU$7.2, AU$6.3) post-HCP periods compared with in the wait time (AU$7.9, AU$7.1). CONCLUSIONS: Increased spending post-HCP on inpatient care or non-health support afforded by HCPs may offer protective effects for mortality and risk of admission to aged care. Further research should explore the association between delayed access to inpatient care for geriatric syndromes and mortality to inform recommendations on extensions to residential care outreach services into the community to improve the timely identification of the need for inpatient care. Geriatr Gerontol Int 2023; 23: 899-905.

One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial.

Rationale: The combination of noradrenergic and antimuscarinic agents has recently been shown to improve upper-airway function and reduce obstructive sleep apnea (OSA) severity in short-term (⩽1 wk) proof-of-concept studies. Objectives: To determine the safety, tolerability, and potential efficacy of longer term use of different doses of the noradrenergic agent atomoxetine combined with the antimuscarinic oxybutynin (ato-oxy). Methods: Thirty-nine people with predominantly severe OSA received 80/5 mg ato-oxy, 40/5 mg ato-oxy, 40/2.5 mg ato-oxy, or placebo nightly for 30 days in a double-blind, randomized, parallel design. Participants completed three in-laboratory sleep studies (baseline, Night 1, and Night 30) to assess efficacy. Vital signs and objective measures of alertness and memory were assessed. In men, potential effects on prostate function were assessed using the International Prostate Symptom Score at baseline and Night 30. Potential adverse events were assessed during in-laboratory visits and via weekly phone calls. Results: Side effects were generally mild and consistent with known side-effect profiles of each individual drug (i.e., dose-dependent increases in dry mouth with oxybutynin). Heart rate increased by Night 30 in two active drug arms (mean ± standard deviation 8 ± 10 beats/min [P = 0.01] with 80/5 mg and 9 ± 14 beats/min [P = 0.02] with 40/2.5 mg vs. placebo). No clinically relevant changes in blood pressure, International Prostate Symptom Score, and measures of alertness and memory were observed between conditions. Apnea-hypopnea index (AHI) with 4% oxygen desaturation and hypoxic burden decreased by ∼50% with 80/5 mg ato-oxy from baseline but not versus placebo (e.g., AHI with 3% oxygen desaturation and AHI with 4% oxygen desaturation difference at Night 30 was -8.2 [95% confidence interval, -22.5 to 6.2] and -8.5 [95% confidence interval, -18.3 to 1.3] events/h, respectively). Conclusions: One month of nightly noradrenergic and antimuscarinic combination therapy was generally well tolerated, with a side-effect profile consistent with each agent alone, and was associated with an ∼50% reduction from baseline in a key OSA severity metric, the hypoxic burden with the highest dose combination. These findings highlight the potential to target noradrenergic and antimuscarinic mechanisms for OSA pharmacotherapy development. Clinical trial registered with www.anzctr.org.au (ACTRN 12619001153101).

The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study.

OBJECTIVES: Previous studies examining associations between sleep spindles and cognitive function attempted to account for obstructive sleep apnea without consideration for potential moderating effects. To elucidate associations between sleep spindles, cognitive function, and obstructive sleep apnea, this study of community-dwelling men examined cross-sectional associations between sleep spindle metrics and daytime cognitive function outcomes following adjustment for obstructive sleep apnea and potential obstructive sleep apnea moderating effects. METHODS: Florey Adelaide Male Ageing Study participants (n = 477, 41-87 years) reporting no previous obstructive sleep apnea diagnosis underwent home-based polysomnography (2010-2011). Cognitive testing (2007-2010) included the inspection time task (processing speed), trail-making tests A (TMT-A) (visual attention) and B (trail-making test-B) (executive function), and Fuld object memory evaluation (episodic memory). Frontal spindle metrics (F4-M1) included occurrence (count), average frequency (Hz), amplitude (µV), and overall (11-16 Hz), slow (11-13 Hz), and fast (13-16 Hz) spindle density (number/minute during N2 and N3 sleep). RESULTS: In fully adjusted linear regression models, lower N2 sleep spindle occurrence was associated with longer inspection times (milliseconds) (B = -0.43, 95% confidence interval [-0.74, -0.12], p = .006), whereas higher N3 sleep fast spindle density was associated with worse TMT-B performance (seconds) (B = 18.4, 95% confidence interval [1.62, 35.2], p = .032). Effect moderator analysis revealed that in men with severe obstructive sleep apnea (apnea-hypopnea index ≥30/hour), slower N2 sleep spindle frequency was associated with worse TMT-A performance (χ2 = 12.5, p = .006). CONCLUSIONS: Specific sleep spindle metrics were associated with cognitive function, and obstructive sleep apnea severity moderated these associations. These observations support the utility of sleep spindles as useful cognitive function markers in obstructive sleep apnea, which warrants further longitudinal investigation.

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

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.

Immediate Effects of Lower Limb Sensory Simulation Using Smart Socks to Stabilize Gait in People with Parkinson's Disease.

People with Parkinson's disease (PD) experience gait impairment that can lead to falls and poor quality of life. Here we investigate the feasibility of using smart socks to stimulate the lower limbs of people with PD to reduce excessive step time variability during walking. We hypothesised that rythmic excitation of lower limb afferents, matched to a participant's comfortable pace, would entrain deficient neuro-muscular signals resulting in improved gait. Five people with mild to moderate PD symptoms (70 ± 9 years) were tested on medication before and after a 30-minute familierization session. Paired t-tests and Cohen's d were used to assess gait changes and report effect sizes. Participant experiences were recorded through structured interviews. Lower limb stimulation resulted in an acute 15% increase in gait speed (p=0.006, d=0.62), an 11% increase in step length (p=0.04, d=0.35), a 44% reduction in step time variability (p=0.03, d=0.91), a 22% increase in perceived gait quality (p=0.04, d=1.17), a 24% reduction in mental effort to walk (p=0.02, d=0.79) and no statistical difference for cadence (p=0.16). Participants commented positively on the benefit of stimulation during training but found that stimulation could be distracting when not walking and the socks hard to put on. While the large effects for step time variability and percieved gait quality (Cohen's d > 0.8) are promising, limitations regarding sample size, potential placebo effects and translation to the home environment should be addressed by future studies.Clinical Relevance- This study demonstrates the feasibility of using smart stimulating socks to reduce excessive step time variability in people with PD. As step time variability is a risk factor for falls, the use of smart textiles to augment future rehabilitation programs warrants further investigation.