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The combination of noradrenergic and anti-muscarinic agents has recently been shown to improve upper-airway function and reduce obstructive sleep apnea (OSA) severity in short-term (≤1 week) proof-of-concept studies.To determine the safety, tolerability, and potential efficacy of longer-term use of different doses of the noradrenergic agent atomoxetine combined with the anti-muscarinic oxybutynin.Thirty-nine people with predominantly severe OSA received either 80mg atomoxetine/5mg oxybutynin (ato-oxy), 40/5mg ato-oxy, 40/2.5mg 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, 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 (IPSS) at baseline and night 30. Potential adverse events were assessed during in-lab visits and via weekly phone calls.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±SD: 8±10 beats/min, p=0.01, 80/5mg; 9±14 beats/min, p=0.02, 40/2.5mg; versus placebo). No clinically relevant changes to blood pressure, IPSS and measures of alertness and memory were observed between conditions. Apnoea-hypopnea index (4% oxygen desaturation: AHI4) and hypoxic burden decreased by ~50% with 80/5mg ato-oxy from baseline but not versus placebo (e.g., AHI3 and AHI4 difference [95%CI] at night 30= -8.2 [-22.5, 6.2] and -8.5 [-18.3, 1.3] events/h, respectively).1 month of nightly noradrenergic and anti-muscarinic 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 anti-muscarinic mechanisms for OSA pharmacotherapy development.ACTRN12619001153101.

STUDY OBJECTIVES: Sleep microarchitecture parameters determined by quantitative power spectral analysis of electroencephalograms have been proposed as potential brain-specific markers of cognitive dysfunction. However, data from community samples remain limited. This study examined cross-sectional associations between sleep microarchitecture and cognitive dysfunction in community-dwelling men. METHODS: Florey Adelaide Male Ageing Study participants (n = 477) underwent home-based polysomnography (2010–2011). All-night electroencephalogram recordings were processed using quantitative power spectral analysis following artifact exclusion. Cognitive testing (2007–2010) included the inspection time task, Trail-Making Tests A and B, and Fuld object memory evaluation. Complete case cognition, polysomnography, and covariate data were available in 366 men. Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders determined cross-sectional associations between sleep microarchitecture and cognitive dysfunction overall and by age-stratified subgroups. RESULTS: In the overall sample, worse Trail-Making Test A performance was associated with higher rapid eye movement (REM) theta and alpha and non-REM theta but lower delta power (all P

Objectives Exergame training is a promising method for delivering evidence-based fall prevention exercise as it can facilitate exercise adherence and can be tailored to address cognitive and motor risk factors for falls. This study examined the effectiveness of two home-based computer game interventions (seated brain training and step training; smart±step) in preventing falls in community-dwelling older people, compared to a minimal-intervention control group. Design Assessor-blinded, randomised controlled trial. Setting Research institute and homes of older people living in the community of Sydney, Australia. Participants 769 people aged 65+ years living independently in the community and free of cognitive impairment, progressive neurological disease, or any other unstable or acute medical condition that precludes exercise. Interventions Participants were randomised to one of three arms: brain training using a computerised touch pad while seated; exergame step training on a computerised mat; or control. The intervention groups were provided with a home-based training system and were asked to train for at least two hours per week over the 12-month trial. Main outcome measures The primary outcome was the rate of falls reported monthly over 12 months. Results Between October 2016 and May 2019, 769 participants were randomised (seated brain training =262, exergame step training=252, control=255) and all were included in the intention-to-treat analyses. The rate of falls over 12 months was significantly reduced in the exergame step training group compared to control (IRR=0.74, 95%CI=0.56 to 0.98) and was not statistically different between the seated brain training and control groups (IRR=0.86, 95%CI=0.65 to 1.12). No serious intervention-related adverse events were reported. Conclusions A home-based exergame step training program provides a safe and effective means for preventing falls in older people living in the community. 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. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12616001325493, registered 22 September 2016.

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

Rationale: There are at least four key pathophysiological endotypes that contribute to obstructive sleep apnea (OSA) pathophysiology. These include 1) upper-airway collapsibility (Pcrit); 2) arousal threshold; 3) loop gain; and 4) pharyngeal muscle responsiveness. However, an easily interpretable model to examine the different ways and the extent to which these OSA endotypes contribute to conventional polysomnography-defined OSA severity (i.e., the apnea–hypopnea index) has not been investigated. In addition, clinically deployable approaches to estimate OSA endotypes to advance knowledge on OSA pathogenesis and targeted therapy at scale are not currently available. Objectives: Develop an interpretable data-driven model to 1) determine the different ways and the extent to which the four key OSA endotypes contribute to polysomnography-defined OSA severity and 2) gain insight into how standard polysomnographic and clinical variables contribute to OSA endotypes and whether they can be used to predict OSA endotypes. Methods: Age, body mass index, and eight polysomnography parameters from a standard diagnostic study were collected. OSA endotypes were also quantified in 52 participants (43 participants with OSA and nine control subjects) using gold-standard physiologic methodology on a separate night. Unsupervised multivariate principal component analyses and data-driven supervised machine learning (decision tree learner) were used to develop a predictive algorithm to address the study objectives. Results: Maximum predictive performance accuracy of the trained model to identify standard polysomnography-defined OSA severity levels (no OSA, mild to moderate, or severe) using the using the four OSA endotypes was approximately twice that of chance. Similarly, performance accuracy to predict OSA endotype categories (“good,” “moderate,” or “bad”) from standard polysomnographic and clinical variables was approximately twice that of chance for Pcrit and slightly lower for arousal threshold. Conclusions: This novel approach provides new insights into the different ways in which OSA endotypes can contribute to polysomnography-defined OSA severity. Although further validation work is required, these findings also highlight the potential for routine sleep study and clinical data to estimate at least two of the key OSA endotypes using data-driven predictive analysis methodology as part of a clinical decision support system to inform scalable research studies to advance OSA pathophysiology and targeted therapy for OSA.

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

Background The evidence to support effective fall prevention strategies in older people with cognitive impairment (CI) is limited. The aim of this randomized controlled trial (RCT) was to determine the efficacy of a fall prevention intervention in older people with CI. Method RCT involving 309 community-dwelling older people with CI. The intervention group (n = 153) received an individually prescribed home hazard reduction and home-based exercise program during the 12-month study period. The control group (n = 156) received usual care. The primary outcome was rate of falls. Secondary outcomes included faller/multiple faller status, physical function, and quality of life. Results Participants’ average age was 82 years (95% CI 82–83) and 49% were female. There was no significant difference in the rate of falls (incidence rate ratio [IRR] 1.05; 95% confidence interval [95% CI] 0.73–1.51). A sensitivity analysis, controlling for baseline differences and capping the number of falls at 12 (4 participants), revealed a nonsignificant reduction in fall rate in the intervention group (IRR 0.78; 95% CI 0.57–1.07). Analyses of secondary outcomes indicated the intervention significantly reduced the number of multiple fallers by 26% (RR 0.74; 95% CI 0.54–0.99) when adjusting for baseline differences. There was a differential impact on falls in relation to physical function (interaction term p-value = .023) with a significant reduction in fall rate in intervention group participants with better baseline physical function (IRR 0.60; 95% CI 0.37–0.98). There were no significant between-group differences for other secondary outcomes. Conclusions This intervention did not significantly reduce the fall rate in community-dwelling older people with CI. The intervention did reduce the fall rate in participants with better baseline physical function. Clinical Trials Registration Number Australian and New Zealand Trials Registry ACTRN12614000603617.

Background: Post-dural puncture headache (PDPH) is an iatrogenic condition following lumbar puncture (LP). Incidence is variable and often associated with young females. Technical features of the procedure (i.e. needle gauge) have been investigated; however there is no investigation on the method of cerebrospinal fluid (CSF) collection. Objective: To investigate whether mild CSF aspiration is associated with increased PDPH in selected patients. Methods: 336 subjects were eligible to the study. Data on 237 patients from a tertiary neurology hospital who underwent diagnostic LP from February 2010 to December 2012 were analysed. Patient demographics, lumbar puncture method, CSF biochemical characteristics, opening pressures, and a follow-up inquire on PDPH occurrence were collected. CSF was collected either by allowing free flow or by mild aspiration. Results: The aspiration arm (n=163) was comprised of 55.8% females with mean age of 52(35‒69) years. Sex distribution was not different between the two arms (p=0.191). A significant larger amount of CSF was obtained in the aspiration arm (p=0.011). The incidence of PDPH in the aspiration arm was 16.5% versus 20.2% in the free flow arm, not statistically significant (p=0.489). No relevant associations emerged from the analyses in the subgroup aged

Obstructive sleep apnea (OSA) is common in people with multiple sclerosis (MS). However, people with MS often do not have "typical" anatomical risk factors (i.e., nonobese and female predominance). Accordingly, nonanatomical factors such as impaired upper-airway muscle function may be particularly important for OSA pathogenesis in MS. Therefore, this study aimed to investigate genioglossus (largest upper-airway dilator muscle) reflex responses to brief pulses of upper-airway negative pressure in people with OSA and MS. Eleven people with MS and OSA and 10 OSA controls without MS matched for age, sex, and OSA severity were fitted with a nasal mask, pneumotachograph, choanal and epiglottic pressure sensors, and intramuscular electrodes into genioglossus. Approximately 60 brief (250 ms) negative pressure pulses (approximately -12 cmH

Background Frailty increases the risk of post-operative complications in older patients, however clinical assessment of frailty is not routinely undertaken. We aimed to evaluate whether the Hospital Frailty Risk Score (HFRS), calculated using data available from ICD-10 coded electronic records at time of admission, could be used to identify patients at risk of complications. Methods Hospital and death data for individuals aged >50 years, admitted for surgery to all hospitals in NSW, Australia 2016-2017 were linked. Hospital-acquired complications (HACs) were identified using 16 categories. Logistic regression models were used to quantify influence of explanatory variables; age, sex, comorbidity, urgency of admission and HFRS on risk of HACs, and model performance assessed. Results Of the 150,355 hospitalisations, 12.3% resulted in a complication. Infections (6.1%) and delirium (3.3%) were the most common complications. 30-day mortality was higher following complication (12.5% vs 1.8%, p 1 complication (OR 2.67, 95%CI 2.57-2.78), followed by multimorbidity (OR 1.90, 95%CI 1.78-2.02) and high HFRS (OR 1.57, 95%CI 1.48-1.66). The fully-fitted model provided acceptable discrimination (AUC 0.72, 95%CI 0.72-0.73). Conclusions The HFRS was strongly associated with complications following surgery. Used in conjunction with age, sex, urgency and comorbidity the HFRS predicted complications with 72% accuracy. Key messages This is the first study to validate the use of HFRS as a screening tool to identify frail patients at risk of developing complications following surgery. The HFRS provides hospitals with an inexpensive, systematic method to screen for high-risk patients at time of admission.

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.

Objectives To describe the injury profile, hospitalisation rates and health outcomes for older people with cognitive impairment and to determine whether these differ from those with normal cognition. Methods Participants were 867 community-dwelling 70–90 year olds enrolled in the population-based longitudinal Sydney Memory and Ageing Study (MAS). Participant’s cognitive status was classified as normal, mild cognitive impairment (MCI) and dementia at baseline, then 2, 4 and 6 years’ follow-up. MAS records were linked to hospital and death records to identify injury-related hospitalisations for the 2-year period following each assessment. Results There were 335 injury-related hospitalisations for participants; 222 (25.6%) participants had at least one injury-related hospitalisation. The injury-related hospitalisation rate for participants with MCI (63.0 [95%CI 51.6–74.4] per 1000 person-years) was higher than for people with normal cognition (39.3 [95%CI 32.4–46.1] per 1000 person-years) but lower than people with dementia (137.1 [95%CI 87.2–186.9] per 1000 person-years). Upper limb fractures (22.1%) were the most common injuries for participants with normal cognition, and non-fracture head injuries for participants with MCI and dementia (25.9% and 23.3% respectively). Participants with dementia had a higher proportion of hip fractures (20.0%, p = 0.0483) than participants with normal cognition. There was no difference in 30-day mortality between participants with normal cognition, MCI and dementia (3.9%, 1.7%, 3.3% respectively). Conclusion Older people with objectively defined MCI are at higher risk of injury-related hospitalisation than their cognitively intact peers, but lower risk than people with dementia. Falls-risk screening and fall prevention initiatives may be indicated for older people with MCI.

Objective To test whether StandingTall, a home based, e-health balance exercise programme delivered through an app, could provide an effective, self-managed fall prevention programme for community dwelling older people. Design Assessor blinded, randomised controlled trial. Setting Older people living independently in the community in Sydney, Australia. Participants 503 people aged 70 years and older who were independent in activities of daily living, without cognitive impairment, progressive neurological disease, or any other unstable or acute medical condition precluding exercise. Interventions Participants were block randomised to an intervention group (two hours of StandingTall per week and health education; n=254) or a control group (health education; n=249) for two years. Main outcome measures The primary outcomes were the rate of falls (number of falls per person year) and the proportion of people who had a fall over 12 months. Secondary outcomes were the number of people who had a fall and the number of injurious falls (resulting in any injury or requiring medical care), adherence, mood, health related quality of life, and activity levels over 24 months; and balance and mobility outcomes over 12 months. Results The fall rates were not statistically different in the two groups after the first 12 months (0.60 falls per year (standard deviation 1.05) in the intervention group; 0.76 (1.25) in the control group; incidence rate ratio 0.82, 95% confidence interval 0.66 to 1.02, P=0.070). Additionally, the proportion of people who fell was not statistically different at 12 months (34.6% in intervention group, 40.2% in control group; relative risk 0.90, 95% confidence interval 0.72 to 1.12, P=0.348). However, the intervention group had a 16% lower rate of falls over 24 months (incidence rate ratio 0.84, 95% confidence interval 0.72 to 0.98, P=0.027) and a 20% lower rate of injurious falls over 24 months compared with the control group (incidence rate ratio 0.80, 95% confidence interval 0.66 to 0.98, P=0.031). Both groups had a similar proportion of people who fell over 24 months (relative risk 0.87, 95% confidence interval 0.74 to 1.02, P=0.077). In the intervention group, 68.1% and 52.0% of participants exercised for a median of 114.0 min/week (interquartile range 53.5) after 12 months and 120.4 min/week (38.6) after 24 months, respectively. Groups remained similar in mood and activity levels. The intervention group had a 0.03 (95% confidence interval 0.01 to 0.06) improvement on the EQ-5D-5L (EuroQol five dimension five level) utility score at six months, and an improvement in standing balance of 11 s (95% confidence interval 2 to 19 s) at six months and 10 s (1 to 19 s) at 12 months. No serious training related adverse events occurred. Conclusions The StandingTall balance exercise programme did not significantly affect the primary outcomes of this study. However, the programme significantly reduced the rate of falls and injurious falls over two years, with similar but not statistically significant effects at 12 months. E-health exercise programmes could provide promising scalable fall prevention strategies. Trial registration ACTRN12615000138583

Introduction Upper airway sensory impairment may contribute to obstructive sleep apnea (OSA) for certain patients. However, the type of sensory impairment and its role in OSA pathogenesis remain unclear. This study aimed to: (1) evaluate methods of upper airway sensory testing in the OSA literature, (2) compare upper airway sensation in people with and without OSA and (3) investigate the relationship between OSA severity and upper airway sensory impairment. Methods Electronic databases were searched up to February 2020 for studies reporting methods of upper airway sensory testing in people with OSA (n=3,819). From the selected studies (n=38), information on the type of sensation, testing methods, validity and reliability were extracted. Meta-analyses were performed on case-controlled studies and studies reporting correlations between upper airway sensation and OSA severity. Results Seven types of upper airway sensation were reported: olfactory, gustatory, chemical, tactile, vibratory, thermal and neuro-sensation. Methods of upper airway sensory testing varied. No tests were validated or assessed for reliability in OSA populations. People with OSA had impaired sensation on airflow (p Conclusions People with OSA demonstrated impaired upper airway sensation, which related to increasing OSA severity. The extent to which upper airway sensation was impaired varied across testing methods. The findings suggest that development of valid and reliable upper airway sensory tests, that relate to upper airway function in people with OSA, are necessary for future clinical and research practices.

IntroductionAs the population ages, increasing numbers of older adults are undergoing surgery. Outcomes for older people are known to be worse than younger people following surgical procedures, and identifying which patients stand to benefit from surgery can be challenging. Frailty is recognised as a major contributor to poor outcomes, however assessing frailty clinically is time-consuming and not routinely undertaken. Using data available from electronic medical records can potentially provide the opportunity to routinely screen for frailty electronically at time of admission. Objectives and ApproachThis population-based external validation study aimed to: 1. assess the performance of the Hospital Frailty Risk Score (HFRS) in the prediction of adverse outcomes (mortality, prolonged length of stay (LOS) and 28-day readmission), 2. to determine optimal age-groups and lookback periods and 3. compare HFRS performance against the Charlson Comorbidity Index (CCI). Hospital and death data for individuals (n=487,197) aged >50 years admitted under a surgical specialty to all public/private hospitals in NSW, Australia, 2013-2017 were linked. Logistic regression models were tested for each outcome of interest. Area under receiving operator curve (AUC) and Akaike information criterion (AIC) were assessed for each model. ResultsFor prediction of 30-day, all models performed better than age and sex alone; however adjusting for CCI (AUC 0.76) provided marginally better prediction than adjusting for HFRS (AUC 0.75). Models consistently performed better in the younger age-group (50-65), providing excellent discrimination (AUC 0.82). In contrast, 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 using a 2-year period. Conclusion / ImplicationsAdjusting for frailty using the HFRS did not improve prediction of 30-mortality over that achieved by the CCI. Neither HFRS nor CCI were useful for predicting prolonged-LOS r 28-day unplanned readmission.

Impaired upper airway sensation may contribute to obstructive sleep apnea (OSA) pathophysiology and could represent a therapeutic target. However, the extent of impaired sensation and its functional role in OSA pathogenesis remains unclear. This study aimed to: 1) evaluate methods of upper airway sensory testing in people with OSA, 2) compare upper airway sensation in people with and without OSA and 3) investigate the potential relationship between upper airway sensation and OSA severity. Major electronic databases were searched for studies that reported methods of upper airway sensory testing in people with OSA (n = 3819). From the selected studies (n = 38), information on the type of sensation, testing methods, validity and test-retest reliability were extracted. Meta-analyses were performed on case-controlled studies and studies that investigated potential relationships between upper airway sensation and OSA severity. Seven categories of sensory tests were reported: olfactory, gustatory, chemical, tactile, vibratory, thermal and perioral neuro-sensation. Testing methods varied widely across studies. No tests were validated in OSA. People with OSA had impaired upper airway sensation to airflow (p = 0.0002), chemical (p = 0.0001), gustatory (p = 0.009), olfactory (p = 0.04), tactile (p = 0.0001) and vibratory (p = 0.005) stimuli. Upper airway sensory impairment increased with OSA severity (p 0.001). These findings suggest that, while variable across testing methods, people with OSA have impaired upper airway sensation, which is related to increased OSA severity. Development of valid and reliable upper airway sensory testing methods that relate to upper airway function in people with OSA are required to inform future clinical and research practices and identify potential therapeutic targets.

Trust in public health officials and the information they provide is essential for the public uptake of preventative strategies to reduce the transmission of COVID-19. This paper discusses how a model for developing and maintaining trust in public health officials during food safety incidents and scandals might be applied to pandemic management. The model identifies ten strategies to be considered, including: transparency; development of protocols and procedures; credibility; proactivity; putting the public first; collaborating with stakeholders; consistency; education of stakeholders and the public; building your reputation; and keeping your promises. While pandemic management differs insofar as the responsibility lies with the public rather than identifiable regulatory bodies, and governments must weigh competing risks in creating policy, we conclude that many of the strategies identified in our trust model can be successfully applied to the maintenance of trust in public health officials prior to, during, and after pandemics.

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.

Background To quantify the incidence and timing of second hip fracture, and to evaluate the relative impact of comorbidities on risk of second hip fracture. Methods Hospitalization records for individuals aged ≥65, admitted to a New South Wales hospital for fall-related hip fracture between 1 January 2005 and 31 December 2009 were linked. Comorbidities were identified from the records using a 1-year look-back period. To calculate second hip fracture rates, individuals were followed until death, fracture or end of study period (31 December 2012). Time-dependent competing-risk hazards regression was used to assess the relative contribution of each comorbidity to fracture risk, adjusting for age and sex. Results Of the 24 500 individuals who sustained at least one hip fracture, 2.9% experienced a second within a year, 6.1% within 3 years and 9.4% within 8 years. Malnutrition/cachexia (hazard ratio (HR): 2.47; 99.9% confidence interval (CI): 1.87-3.26), dementia (HR: 2.15; 99.9% CI: 1.80-2.57), congestive heart failure (HR: 1.62; 99.9% CI: 1.30-2.04), Parkinson's disease (HR: 1.51; 99.9% CI: 1.08-2.10), cerebrovascular disease (HR: 1.41; 99.9% CI: 1.06-1.89) and osteoporosis (HR: 1.36; 99.9% CI: 1.11-1.67) were associated with increased risk of second hip fracture within 3 years. Mortality was high; with 26% of individuals dying within a year, 44.9% within 3 years and 70.2% within 8 years. Conclusions One in 11 older individuals with an initial hip fracture sustained a second hip fracture. While the priority is to prevent the first hip fracture, those that have sustained a hip fracture should be seen as a high risk population and be targeted for future falls and fracture prevention strategies.

Introduction and Aims The extent to which young adult former cannabis users fare better than infrequent users is unclear. We investigated the association between cannabis use status at age 23 and substance use and mental health outcomes at age 27. Design and Methods Data were from the 20+ year cohort of the PATH Through Life Study. Lifetime cannabis users (n = 1410) at age 23 were classified as former/occasional/regular users. Multivariable logistic regression was used to estimate the association between cannabis use status at age 23 and six outcomes assessed at age 27. Results Compared with occasional cannabis users: (i) former users had odds of subsequent tobacco use [odds ratio (OR) = 0.67, 95% confidence interval (CI) 0.52–0.85], illicit drug use (cannabis, OR = 0.22, 95% CI 0.17–0.28; other illicit drugs, OR = 0.29, 95% CI 0.22–0.39) and mental health impairment (OR = 0.71, 95% CI 0.55–0.92) that were 29–78% lower; and (ii) regular users had odds of subsequent frequent alcohol use (OR = 2.34, 95% CI 0.67–1.34), tobacco use (OR = 3.67, 95% CI 2.54–5.30), cannabis use (OR = 11.73, 95% CI 6.81–20.21) and dependence symptoms (OR = 12.60, 95% CI 8.38–18.94), and other illicit drug use (OR = 2.95, 95% CI 2.07–4.21) that were 2–13 times greater. Associations attenuated after covariate adjustment, and most remained significant. Discussion and Conclusions Clear associations exist between cannabis use status in young adulthood and subsequent mental health and substance use. While early intervention remains important to prevent regular cannabis use and the associated harms, experimentation with cannabis use in the years leading into young adulthood may not necessarily determine an immutable pathway to mental health problems and illicit substance use. [Silins E, Swift W, Slade T, Toson B, Rodgers B, Hutchinson DM. A prospective study of the substance use and mental health outcomes of young adult former and current cannabis users. Drug Alcohol Rev 2017;00:000-000]

OBJECTIVE To systematically examine stepping performance as a risk factor for falls. More specifically, we examined (i) if step tests can distinguish fallers from non-fallers and (ii) the type of step test (e.g. volitional vs reactive stepping) that is required to distinguish fallers from non-fallers. DATA SOURCE PubMed, EMBASE, CINAHL, Cochrane Database of Systematic Reviews and reference lists of included articles. STUDY SELECTION Cross-sectional and cohort studies that assessed the association between at least one step test and falls in older people (age ≥ 60 and/or mean age of 65). RESULTS A meta-analysis of 61 studies (n = 9536) showed stepping performance was significantly worse in fallers compared to non-fallers (Cohen'sd 0.56, 95 % CI 0.48 to 0.64, p < 0.001, I2 66 %). This was the case for both volitional and reactive step tests. Twenty-three studies (n = 3615) were included in a diagnostic meta-analysis that showed that step tests have moderate sensitivity (0.70, 95 % CI 0.62 to 0.77), specificity (0.68, 95 % CI 0.58 to 0.77) and area under the receiver operating characteristics curve (AUC) (0.75, 95 % CI 0.59 to 0.86) in discriminating fallers from non-fallers. CONCLUSIONS This large systematic review demonstrated that both volitional and reactive stepping impairments are significant fall risk factors among older adults. Step tests can identify fallers from non-fallers with moderate accuracy.

Prospective cohort study. For acute traumatic spinal cord injury (ATSCI), this study aimed to determine differences in outcomes between patient groups stratified by admission time (⩽24 vs >24 h) to the Spinal Injury Unit (SIU) and by the nature of the admission (direct admission to the SIU vs indirect admission via another hospital). We also aimed to measure the effect on time to admission of a ‘non-refusal’ policy that triggered immediate acceptance of ATSCI cases to the SIU. New South Wales, Australia. Study population was all adult SCI patients admitted to the Prince of Wales SIU from 1 January 2001 to 31 December 2012. Patients admitted with chronic-stage SCI or with incomplete data for the duration of their stay were excluded. Comparison of outcomes was made between groups according to the setting of admission. Time to admission before and after initiation (2009) of the ‘non-refusal’ policy was compared. The prevalence of complications, lengths of stay (LOSs) and time to admission were compared by Mann–Whitney non-parametric methods. Count modelling was used to control for confounders of age and gender. A total of 460 cases were identified and 76 were excluded. The early group had fewer pressure areas (41.8% vs 63.2%; P

© 2015 Asian Pacific Society of Respirology. 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.

Study ObjectivesA collapsible or crowded pharyngeal airway is the main cause of obstructive sleep apnea (OSA). However, quantification of airway collapsibility during sleep (Pcrit) is not clinically feasible. The primary aim of this study was to compare upper airway collapsibility using a simple wakefulness test with Pcrit during sleep.MethodsParticipants with OSA were instrumented with a nasal mask, pneumotachograph and two pressure sensors, one at the choanae (PCHO), the other just above the epiglottis (PEPI). Approximately 60 brief (250 ms) pulses of negative airway pressure (~ –12 cmH2O at the mask) were delivered in early inspiration during wakefulness to measure the upper airway collapsibility index (UACI). Transient reductions in the continuous positive airway pressure (CPAP) holding pressure were then performed during sleep to determine Pcrit. In a subset of participants, the optimal number of replicate trials required to calculate the UACI was assessed.ResultsThe UACI (39 ± 24 mean ± SD; range = 0%–87%) and Pcrit (–0.11 ± 2.5; range: –4 to +5 cmH2O) were quantified in 34 middle-aged people (9 female) with varying OSA severity (apnea–hypopnea index range = 5–92 events/h). The UACI at a mask pressure of approximately –12 cmH2O positively correlated with Pcrit (r = 0.8; p < 0.001) and could be quantified reliably with as few as 10 replicate trials. The UACI performed well at discriminating individuals with subatmospheric Pcrit values [receiver operating characteristic curve analysis area under the curve = 0.9 (0.8–1), p < 0.001].ConclusionsThese findings indicate that a simple wakefulness test may be useful to estimate the extent of upper airway anatomical impairment during sleep in people with OSA to direct targeted non-CPAP therapies for OSA.

IntroductionData-linkage studies using administrative hospital data have shown that people with dementia have double the rate of injury-related hospitalisations and poorer health outcomes than those without. No previous research has explored whether people with mild cognitive impairment are also at increased risk of serious injury requiring hospitalisation. Objectives and ApproachA major barrier to the use of administrative hospital data for undertaking research focusing on people with MCI is that MCI cannot be reliably identified from ICD-10 coded administrative data. To overcome this limitation, hospitalisation and death data was linked to data from participants (community-dwelling 70-90 year olds) enrolled in the population-based longitudinal Sydney Memory and Ageing Study (MAS). MAS participants underwent comprehensive neuropsychological assessments at baseline, then 2, 4 and 6 years’ follow-up to accurately determine cognitive status at each time-period. Linkage to hospital records allowed identification of injury-related hospitalisations and outcomes for the 2-year period following each assessment. ResultsThere were 335 injury-related hospitalisations for the 867 participants; 222 (25.6%) participants had at least one injury-related hospitalisation. After adjusting for age-and-sex, participants in a state of MCI had 1.7 (95%CI 1.2-2.4) times higher odds of an injury-related hospitalisation than participants in a state of normal cognition, whilst participants with dementia had 2.3 (95%CI 1.2-4.4) times higher odds. There was no difference in odds between participants with MCI and dementia. Of the 116 hospitalisations for people with MCI, the majority (79.3%) were due to falls. Non-fracture head injuries (25.9%), upper limb and trunk fractures (13.8% respectively) were the most common injury type. There were no differences in injury type, mean length of stay, or 30-day mortality between people with normal cognition, MCI and dementia. Conclusion/ImplicationsOlder people with objectively defined MCI are at higher risk of injury, predominantly as a result of falls, than their cognitively intact peers. Falls-risk screening and fall prevention initiatives may be indicated for people with MCI. Further research is required to determine which cognitive domains contribute to this increased risk.

INTRODUCTIONThis study aimed to determine if repeated exposure to unpredictable trips and slips while walking can improve balance recovery responses when predictive gait alterations (e.g. slowing down) are minimised.METHODSTen young adults walked on a 10-m walkway that induced slips and trips in fixed and random locations. Participants were exposed to a total of 12 slips, 12 trips and 6 non-perturbed walks in three conditions: 1) right leg fixed location, 2) left leg fixed location and 3) random leg and location. Kinematics during non-perturbed walks and previous and recovery steps were analysed.RESULTSThroughout the three conditions, participants walked with similar gait speed, step length and cadence(p>0.05). Participants’ extrapolated centre of mass (XCoM) was anteriorly shifted immediately before slips at the fixed location (pppCONCLUSIONSEven in the absence of most predictive gait alterations, balance recovery responses to trips and slips were improved through exposure to repeated unpredictable perturbations. A common predictive gait alteration to lean forward immediately before a slip was not useful when the perturbation location was unpredictable. Training balance recovery with unpredictable perturbations may be beneficial to fall avoidance in everyday life.

The aim of this study was to investigate physical decline over 1-year in a cohort of older people across the cognitive spectrum.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.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.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.

Study objectives A negative intrathoracic pressure threshold is one commonly proposed mechanism for triggering respiratory-induced arousals in obstructive sleep apnea (OSA). If so, they should occur during inspiration, shortly after maximal negative pressure swings. Alternatively, respiratory-induced arousals may occur throughout the respiratory cycle if other mechanisms also contribute. However, arousal timing has been minimally investigated. This study aimed to (1) determine the temporal relationship between respiratory-induced arousals and breathing phase and (2) characterize neuromuscular and load compensation responses prior to arousal. Methods Fifty-one CPAP-treated OSA patients underwent a sleep physiology study with genioglossus and tensor palatini EMG, nasal mask/pneumotachograph, and epiglottic pressure. Transient CPAP reductions were delivered to induce respiratory-related arousals. Results Of 354 arousals, 65(60-70)%[mean(CI)] occurred during inspiration, 35(30-40)% during expiration. Nadir epiglottic pressure occurred 68(66-69)% into inspiration while inspiratory arousals had a uniform distribution throughout inspiration. Expiratory arousals occurred predominantly in early expiration. CPAP reductions initially reduced minute ventilation by ~2.5 liter/min, which was restored immediately prior to expiratory but not inspiratory arousals. Duty cycle just prior to arousal was greater for inspiratory versus expiratory arousals [0.20(0.18-0.21) vs. 0.13(0.11-0.15)Δbaseline, p = 0.001]. Peak tensor palatini EMG was higher for expiratory versus inspiratory arousals during prearousal breaths [7.6(5.8-9.6) vs. 3.7(3.0-4.5)%Δbaseline, p = 0.001], whereas genioglossus and tonic tensor palatini EMG were similar between arousal types. Conclusions Over one third of respiratory-induced arousals occur during expiration. These findings highlight the importance of nonpressure threshold mechanisms of respiratory-induced arousals in OSA and suggest that expiratory arousals may be a novel marker of enhanced tensor palatini neuromuscular compensation.

Background The risk of serious injury or death has been found to be reduced for some front compared to rear seat car passengers in newer vehicles. However, differences in injury severity between car occupants by seating position has not been examined. This study examines the injury severity risk for rear compared to front seat car passengers. Method A retrospective matched-cohort analysis was conducted of vehicle crashes involving injured rear vs front seat car passengers identified in linked police-reported, hospitalisation and emergency department (ED) presentation records during 2001–2011 in New South Wales (NSW), Australia. Odds ratios were estimated using an ordinal logistic mixed model and logistic mixed models. Results There were 5419 front and 4588 rear seat passengers in 3681 vehicles. There was a higher odds of sustaining a higher injury severity as a rear-compared to a front seat car passenger, with a higher odds of rear seat passengers sustaining serious injuries compared to minimal injuries. Where the vehicle occupant was older, travelling in a vehicle manufactured between 1990 and 1996 or after 1997, where the airbag deployed, and where the vehicle was driven where the speed limit was ≥70 km/h there was a higher odds of the rear passenger sustaining a higher injury severity then a front seated occupant. Conclusion Rear seat car passengers are sustaining injuries of a higher severity compared to front seat passengers travelling in the same vehicle, as well as when travelling in newer vehicles and where the front seat occupant is shielded by an airbag deployed in the crash. Rear seat occupant protective mechanisms should be examined. Pre-hospital trauma management policies could influence whether an individual is transported to a hospital ED, thus it would be beneficial to have an objective measure of injury severity routinely available in ED records. Further examination of injury severity between rear and front seat passengers is warranted to examine less severe non-fatal injuries by car seating position and vehicle intrusion.

Objectives To evaluate the performance of the Charlson Comorbidity Index (CCI) in the prediction of mortality, 30-day readmission, and length of stay (LOS) in a hip fracture population using algorithms designed for use in International Classification of Diseases, 10th Revision (ICD-10)–coded administrative data sets. Study Design and Setting Hospitalization and death data for 47,698 New South Wales residents aged 65 years and over, admitted for hip fracture, were linked. Comorbidities were ascertained using ICD-10 coding algorithms developed by Sundararajan (2004) and Quan (2005). Regression models were fitted, and area under the receiver operating curve (AUC) and Akaike information criterion were assessed. Results Both algorithms had acceptable discrimination in predicting in-hospital (AUC, 0.72–0.76), 30-day (0.72–0.75), and 1-year mortality (0.69–0.75) but poor ability to predict 30-day readmission (0.54–0.57) or LOS (adjusted R 2 , 0.007–0.045). The Quan algorithm provided better model fit than the Sundararajan algorithm. Models incorporating comorbidities as individual variables performed better than the Charlson weighted or updated Quan weighted score. Including a 1-year lookback period increased predictive ability for 1-year mortality only. Conclusion The CCI is a valid tool for predicting mortality but not resource utilization after hip fracture. We recommend the use of the Quan algorithm rather than Sundararajan algorithm and to model individual conditions rather than categorized weighted scores.

To quantify the incidence and timing of second hip fracture, and to evaluate the relative impact of comorbidities on risk of second hip fracture.Hospitalization records for individuals aged ≥65, admitted to a New South Wales hospital for fall-related hip fracture between 1 January 2005 and 31 December 2009 were linked. Comorbidities were identified from the records using a 1-year look-back period. To calculate second hip fracture rates, individuals were followed until death, fracture or end of study period (31 December 2012). Time-dependent competing-risk hazards regression was used to assess the relative contribution of each comorbidity to fracture risk, adjusting for age and sex.Of the 24 500 individuals who sustained at least one hip fracture, 2.9% experienced a second within a year, 6.1% within 3 years and 9.4% within 8 years. Malnutrition/cachexia (hazard ratio (HR): 2.47; 99.9% confidence interval (CI): 1.87-3.26), dementia (HR: 2.15; 99.9% CI: 1.80-2.57), congestive heart failure (HR: 1.62; 99.9% CI: 1.30-2.04), Parkinson's disease (HR: 1.51; 99.9% CI: 1.08-2.10), cerebrovascular disease (HR: 1.41; 99.9% CI: 1.06-1.89) and osteoporosis (HR: 1.36; 99.9% CI: 1.11-1.67) were associated with increased risk of second hip fracture within 3 years. Mortality was high; with 26% of individuals dying within a year, 44.9% within 3 years and 70.2% within 8 years.One in 11 older individuals with an initial hip fracture sustained a second hip fracture. While the priority is to prevent the first hip fracture, those that have sustained a hip fracture should be seen as a high risk population and be targeted for future falls and fracture prevention strategies.

Background Guidelines for hip fracture care suggest that patients with hip fracture should undergo surgery on the day of or day after admission to hospital. This study examined factors affecting time to surgery for hip fracture extracted from existing administrative datasets in New South Wales (NSW), Australia. Method A retrospective analysis of patients with hip fracture aged 65 years and over undergoing surgical intervention in NSW public hospitals between 1 July 2000 and 30 June 2011. A multinomial logistic model was used to identify factors impacting on time to surgery from 1 July 2006 to 30 June 2011. Results A total of 49 317 hip fracture procedures were recorded during 2000–2001 to 2010–2011. Sixty-four per cent of patients received operative treatment on the day of or day after admission. Co-morbidity, type of surgical procedure and day of presentation all impacted significantly on time to surgery. Fourteen per cent required an inter-hospital transfer prior to receiving operative intervention. Transferred patients were 2.6 (95% confidence interval (CI): 2.31–2.85) times more likely to wait 2–4 days and 3.2 times more likely to wait 5 or more days (95% CI: 2.77–3.76) for surgery compared with patients presenting to an operating hospital. Conclusion Significant variation exists between hospitals in the time to surgery that is not solely explained by measures of case mix or geography. Opportunities exist to consider other factors contributing to this variation and to ensure timely access to surgical intervention in the future.

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.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).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; p0.0001) (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; p0.0001) (imputed data AUC 0.69 (95% CI 0.66-0.72)).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.