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Objective: To examine the frequency of deaths in low-mortality diagnosis-related groups (LM-DRGs) and the patient and hospital characteristics associated with them.Design, Setting and Patients: Retrospective cohort study of 2,400,089 discharge episodes for adults (> 18 years) from 122 Victorian public hospitals from 1 July 2006 to 30 June 2008.Main Outcome Measures: Frequency of episodes of death in LM-DRGs (defined as DRGs with mortality < 0.5% over the previous 3 years or < 0.5% in any of the previous 3 years); associations between characteristics of patients and hospitals with deaths in LM-DRGs.Results: There were 1,008, 816 LM-DRG episodes with 0-15 LM-DRG deaths per hospital in the 2006-07 financial year and 0-20 deaths per hospital in the 2007-08 financial year. Increased age, level of comorbidity, being male, admission from a residential aged care facility, interhospital transfer, emergency admission and lower hospital volume were associated with an increased risk of death in LM-DRG episodes in both years. Metropolitan location and teaching/major provider status were not associated with LM-DRG deaths (P > 0.10). More than 40% of LM-DRG deaths were among patients aged 83 years or over, who had a length of stay of less than 1 day and had a medical DRG classification. Standardised mortality ratios (SMRs) that adjusted for the patient and hospital characteristics identified nine outlier hospitals with high frequencies of deaths in LM-DRGs in the 2006-07 and six in the 2007-08 financial year compared with 59 hospitals flagged by the death-in-LM-DRG indicator.Conclusions: The use of the LM-DRG indicator requires further investigation to test its validity. LM-DRG deaths are infrequent, making it difficult to identify temporal changes and outlier hospitals. Patient characteristics unrelated to quality of care increase the likelihood of death among LM-DRG patients. The SMR analysis showed that failure to adjust for these characteristics may result in unfair and inaccurate identification of outlier hospitals. The increased risk of death associated with interhospital transfer patients and low-volume hospitals requires further investigation. [ABSTRACT FROM AUTHOR]

Australian Health Ministers have endorsed the hospital standardised mortality ratio (HSMR) as a key indicator of quality and safety, and efforts are currently underway towards its national implementation. In the United Kingdom, Canada, the Netherlands and the United States, the HSMR has been used for several years within organisations to monitor performance and response to various quality and safety programs. In the UK and Canada, the HSMR is also publicly reported and used to compare performance between hospitals. The validity and reliability of the HSMR as a screening tool for distinguishing low-quality from high-quality hospitals remain in doubt, and it has not yet been proven that HSMR reporting necessarily leads to worthwhile improvement in quality of care and patient outcomes. Institutions may respond to an unfavourable HSMR by "gaming" administrative data and risk-adjustment models or implementing inappropriate changes to care. Despite its apparent low cost and ease of measurement, the HSMR is currently not "fit for purpose" as a screening tool for detecting low-quality hospitals and should not be used in making interhospital comparisons. It may be better suited to monitoring changes in outcomes over time within individual institutions. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this study was to investigate 3D flow patterns and vessel wall parameters in patients with dilated ascending aorta, age-matched subjects, and healthy volunteers. Methods Thoracic time-resolved 3D phase contrast CMR with 3-directional velocity encoding was applied to 33 patients with dilated ascending aorta (diameter ≥40 mm, age=60±16 years), 15 age-matched normal controls (diameter ≤37 mm, age=68±7.5 years) and 15 young healthy volunteers (diameter ≤30 mm, age=23±2 years). 3D blood flow was visualized and flow patterns were graded regarding presence of supra-physiologic-helix and vortex flow using a semi-quantitative 3-point grading scale. Blood flow velocities, regional wall shear stress (WSS), and oscillatory shear index (OSI) were quantified. Results Incidence and strength of supra-physiologic-helix and vortex flow in the ascending aorta (AAo) was significantly higher in patients with dilated AAo (16/33 and 31/33, grade 0.9±1.0 and 1.5±0.6) than in controls (2/15 and 7/15, grade 0.2 ± 0.6 and 0.6 ± 0.7, PPPPPPPP Conclusions Increase in AAo diameter is significantly correlated with the presence and strength of supra-physiologic-helix and vortex formation in the AAo, as well with decrease in systolic WSS and increase in OSI.

Abstract Background The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2). We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency. Methods The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National Registry. Nine SNPs in LOC123688, CHRNA3 and IREB2 were selected for genotyping. FEV1 percent of predicted and FEV1/FVC ratio were analyzed as quantitative phenotypes. Family-based association analysis was performed in the AAT Genetic Modifiers Study. In the replication set, general linear models were used for quantitative phenotypes and logistic regression models were used for the presence/absence of emphysema or COPD. Results Three SNPs (rs2568494 in IREB2, rs8034191 in LOC123688, and rs1051730 in CHRNA3) were associated with pre-bronchodilator FEV1 percent of predicted in the AAT Genetic Modifiers Study. Two SNPs (rs2568494 and rs1051730) were associated with the post-bronchodilator FEV1 percent of predicted and pre-bronchodilator FEV1/FVC ratio; SNP-by-gender interactions were observed. In the UK National Registry dataset, rs2568494 was significantly associated with emphysema in the male subgroup; significant SNP-by-smoking interactions were observed. Conclusions IREB2 and CHRNA3 are potential genetic modifiers of COPD phenotypes in individuals with severe AAT deficiency and may be sex-specific in their impact.

Abstract Background Neuronal phenotypes associated with hemizygosity of individual genes within the 22q11.2 deletion syndrome locus hold potential towards understanding the pathogenesis of schizophrenia and autism. Included among these genes is Dgcr8, which encodes an RNA-binding protein required for microRNA biogenesis. Dgcr8 haploinsufficient mice (Dgcr8+/-) have reduced expression of microRNAs in brain and display cognitive deficits, but how microRNA deficiency affects the development and function of neurons in the cerebral cortex is not fully understood. Results In this study, we show that Dgcr8+/- mice display reduced expression of a subset of microRNAs in the prefrontal cortex, a deficit that emerges over postnatal development. Layer V pyramidal neurons in the medial prefrontal cortex of Dgcr8+/- mice have altered electrical properties, decreased complexity of basal dendrites, and reduced excitatory synaptic transmission. Conclusions These findings demonstrate that precise microRNA expression is critical for the postnatal development of prefrontal cortical circuitry. Similar defects in neuronal maturation resulting from microRNA deficiency could represent endophenotypes of certain neuropsychiatric diseases of developmental onset.

Objective: This study aimed to examine the association between concentrations of sex hormone binding globulin (SHBG) and fracture risk in community-dwelling older women and explore whether this was explained by the genetic regulation of SHBG., Methods: This prospective cohort study examined 4871 women aged ≥70 years who were not taking medications influencing SHBG concentrations. A genome-wide association study was undertaken to identify single nucleotide polymorphisms (SNPs) associated with SHBG concentrations. Incident fracture was confirmed by medical imaging and adjudicated by expert review committee., Results: The median age of participants was 74.0 years. Over 3.9 (standard deviation 1.4) years of follow-up, 484 participants had an incident fracture. There was a linear trend for a positive association between SHBG concentrations and fracture risk ( p  = 0.001), with the highest SHBG quartile associated with a significantly greater fracture risk compared with the lowest quartile (hazard ratio 1.54, 95% confidence interval 1.16-2.04, p  = 0.003), adjusting for age, body mass index, alcohol consumption, smoking, diabetes, impaired renal function, treatment allocation, medications affecting bone and high-density lipoprotein cholesterol. Two independent SNPs were associated with SHBG concentrations, rs10822163 and rs727428, but neither was associated with fracture risk., Conclusion: SHBG concentrations were positively associated with a greater fracture risk in community-dwelling women aged ≥70 years, which was not explained by genetic variants associated with SHBG regulation.

Context: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodeling., Objective: We examined the associations between levels of phosphate, calcium (Ca), and alkaline phosphatase (ALP), and fracture risk in initially healthy older individuals., Methods: A post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16 703 Australian participants aged 70 years and older and 2411 US participants aged 65 years and older. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and ALP measurement. Fracture data were collected post randomization. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. Phosphate, Ca, and ALP were analyzed in deciles (D1-D10), with deciles 4 to 7 (31%-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations., Results: Of the 9915 participants, 907 (9.2%) individuals had incident fractures recorded over 3.9 (SD 1.4) years. In the fully adjusted model, men in the top decile (D10) of phosphate had a 78% higher risk of incident fracture (HR 1.78; 95% CI, 1.25-2.54). No such association was observed for women (HR 1.09; 95% CI, 0.83-1.44). The population attributable fraction in men within the D10 phosphate category is 6.9%., Conclusion: This result confirms that high-normal serum phosphate levels are associated with increased fracture risk in older men., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: Both grip strength and gait speed can be used as markers of muscle function, however, no previous study has examined them in the same population with respect to risk of falls., Methods: In this prospective cohort study, utilising data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and ASPREE-Fracture substudy, we analysed the association of grip strength and gait speed and serious falls in healthy older adults. Grip strength was measured using a handheld dynamometer and gait speed from 3-metre timed walks. Serious falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations with falls., Results: Over an average of 4.0±1.3 years, amongst 16,445 participants, 1,533 had at least one serious fall. After adjustment for age, sex, physical activity, body mass index, Short Form 12 (state of health), chronic kidney disease, polypharmacy and aspirin, each standard deviation (SD) lower grip strength was associated with 27% (HR 1.27, 95% CI 1.17-1.38) higher risk of falls. The results remained the same for males and females. There was a dose-response relationship in the association between grip strength and falls risk. The higher risk of falls was observed in males in all body mass index (BMI) categories, but only in obese females. The association between gait speed and falls risk was weaker than the association between grip strength and falls risk., Conclusions: All males and only obese females with low grip strength appear to be at the greatest risk of serious falls. These findings may assist in early identification of falls., Competing Interests: Dr Hussain is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198), Professor McNeil is supported through an NHMRC Leadership Fellowship (IG 1173690). No other disclosures are reported by the other authors., (Copyright: © 2023 Pham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To examine the feasibility and acceptability of a falls prevention e-learning program for physiotherapists working with people with osteoarthritis (OA)., Methods: A prospective pre-post quasi-experimental approach was adopted. An e-learning program on falls prevention specific to the OA population was developed and delivered. Feasibility and acceptability data were obtained from recruitment records, Moodle TM activity logs, multiple choice quizzes and customized surveys., Results: Of the 65 physiotherapists and near-graduate physiotherapy students who met the eligibility criteria, 50 (77%) completed the e-learning program. Participants were satisfied and considered the program to be acceptable. The program met their expectations (n = 45; 90%) and was highly relevant to their work (median 8-10 [interquartile range (IQR)] 2; range 0 [not at all relevant] to 10 [extremely relevant]). An overall improvement in knowledge was also observed (mean percentage difference 8%; 95% CI -3.49, -1.27)., Discussion: Given a heightened risk of falls among people with OA, ensuring physiotherapists are skilled in falls prevention is important. Our acceptability and outcomes data indicate that a falls prevention e-learning program can be feasibly delivered to physiotherapists working in OA care. Future research should assess subsequent changes in clinical practice to determine whether physiotherapists deliver care reflective of contemporary falls prevention evidence.

Importance: Increased levels of high-density lipoprotein cholesterol (HDL-C) have been associated with osteoporosis. Preclinical studies have reported that HDL-C reduces bone mineral density by reducing osteoblast number and function. However, the clinical significance of these findings is unclear., Objective: To determine whether higher HDL-C levels are predictive of an increased fracture risk in healthy older adults., Design, Setting, and Participants: This cohort study is a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE-Fracture substudy. ASPREE was a double-blind, randomized, placebo-controlled primary prevention trial of aspirin that recruited participants between 2010 and 2014. These comprised community-based older adults (16 703 Australians aged ≥70 years, 2411 US participants ≥65 years) without evident cardiovascular disease, dementia, physical disability, and life-limiting chronic illness. The ASPREE-Fracture substudy collected data on fractures reported postrandomization from Australian participants. Cox regression was used to calculate hazard ratio (HR) and 95% CI. Data analysis for this study was performed from April to August 2022., Exposure: Plasma HDL-C., Main Outcomes and Measures: Fractures included were confirmed by medical imaging and included both traumatic and minimal trauma fractures. Fractures were adjudicated by an expert review panel., Results: Of the 16 262 participants who had a plasma HDL-C measurement at baseline (8945 female participants [55%] and 7319 male [45%]), 1659 experienced at least 1 fracture over a median (IQR) of 4.0 years (0.02-7.0 years). In a fully adjusted model, each 1-SD increment in HDL-C level was associated with a 14% higher risk of fractures (HR, 1.14; 95% CI, 1.08-1.20). The results remained similar when these analyses were stratified by sex. Sensitivity and stratified analyses demonstrated that these associations persisted when the analyses were repeated to include only (1) minimal trauma fractures, (2) participants not taking osteoporosis medications, (3) participants who were never smokers and reported that they did not drink alcohol, and (4) participants who walked outside for less than 30 minutes per day and reported no participation in moderate/vigorous physical activity and to examine only (5) statin use. No association was observed between non-HDL-C levels and fractures., Conclusions and Relevance: This study suggests that higher levels of HDL-C are associated with an increased fracture risk. This association was independent of common risk factors for fractures.

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

Background: Impaired cerebral blood flow has been associated with an increased risk of falls. Mean arterial pressure (MAP) and variability in MAP have been reported to affect cerebral blood flow but their relationships to the risk of falls have not previously been reported., Methods: Utilising data from the Aspirin in Reducing Events in the Elderly trial participants, we estimated MAP and variability in MAP, defined as within-individual SD of MAP from baseline and first 2 annual visits. The relationship with MAP was studied in 16 703 participants amongst whom 1539 falls were recorded over 7.3 years. Variability in MAP was studied in 14 818 of these participants who experienced 974 falls over 4.1 years. Falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratio and 95% CI for associations with falls., Results: Long-term variability in MAP was not associated with falls except amongst frail or prefrail participants using antihypertensive medications. Within this group each 5 mm Hg increase in long-term variability in MAP increased the risk of falls by 16% (hazard ratio, 1.16 [95% CI, 1.02-1.33]). Amongst the antihypertensive drugs studied, beta-blocker monotherapy (hazard ratio, 1.93 [95% CI, 1.17-3.18]) was associated with an increased risk of falls compared with calcium channel blockers., Conclusions: Higher levels of long-term variability in MAP increase the risk of serious falls in older frail and prefrail individuals taking antihypertensive medications. The observation that the relationship was limited to frail and prefrail individuals might explain some of the variability of previous studies linking blood pressure indices and falls.

Aim: Venous leg ulcers are lower limb skin ulcers characterised by a cycle of healing and recurrence due to underlying chronic venous insufficiency. While compression improves healing outcomes, many ulcers do not heal. As a daily 300 mg oral dose of aspirin in conjunction with compression may improve healing outcomes, we investigated the effect of adjuvant aspirin on venous leg ulcer healing in participants already receiving compression., Materials and Methods: We conducted a prospective, randomised, double-blinded, placebo-controlled, clinical trial (known as ASPiVLU). Participants were recruited from six wound clinics in Australia. We screened 844 participants. Community-dwelling adult participants identified at six hospital outpatient clinics and clinically diagnosed with a venous leg ulcer present for 6+ weeks were eligible between April 13, 2015 to June 30, 2018. We randomised 40 participants (n = 19 aspirin, n = 21 placebo) and evaluated against the primary outcome. There were no dropouts. Ten serious adverse events in six participants were recorded. None were study related. The primary outcome measure was healing at 12 weeks based on blinded assessment., Results: We found no difference in the number of ulcers healed at 12 weeks between the intervention and control groups., Conclusion: This study could not detect whether or not aspirin affected VLU healing speed. This is likely because we recruited fewer participants than expected due to the high number of people with venous leg ulcers in Australia who were already taking Aspirin; future research should investigate other adjuvant therapies or different study designs., (Copyright © 2021 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

Rationale and Objectives: The relationships between computed tomography (CT) pulmonary vascularity and MRI ventilation is not well-understood in chronic obstructive pulmonary disease (COPD) patients. Our objective was to evaluate CT pulmonary vascular and MRI ventilation measurements in ex-smokers and to investigate their associations and how such measurements change over time., Materials and Methods: Ninety ex-smokers (n = 41 without COPD 71 ± 10 years and n = 49 COPD 71 ± 8 years) provided written informed-consent to an ethics-board approved protocol and underwent imaging and pulmonary-function-tests twice, 31 ± 7 months apart. 3 He MRI was acquired to generate ventilation-defect-percent (VDP). CT measurements of the relative area-of-the-lung with attenuation <-950 Hounsfield units (RA 950 ), pulmonary vascular total-blood-volume (TBV) and percent of vessels with radius < one voxel (PV 1 ) were evaluated., Results: At baseline, there were significant differences in RA 950 (p = 0.0001), VDP (p = 0.0001), total-blood-volume (p = 0.0001) and PV 1 (p = 0.01) between ex-smokers and COPD participants as well as for VDP (p = 0.0001) in COPD participants with and without emphysema. The annual FEV 1 change (-40 ± 93 mL/year) was not different among participant subgroups (p = 0.87), but the annual RA 950 (p = 0.01) and PV 1 (p = 0.007) changes were significantly different in participants with an accelerated annual FEV 1 decline as compared to participants with a diminished annual FEV 1 decline. There were significant but weak relationships for PV 1 with FEV 1%pred (p = 0.02), FEV 1 /FVC (p = 0.001), and log RA 950 (p = 0.0001), but not VDP (p=0.20). The mean change in PV 1 was also weakly but significantly related to the change in RA 950 (p = 0.02)., Conclusion: CT pulmonary vascular measurements were significantly different in ex-smokers and participants with COPD and related to RA 950 but not VDP worsening over 2.5 years., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Protoporphyrinogen oxidase (PPO) is a critical enzyme across life as the last common step in the synthesis of many metalloporphyrins. The reaction mechanism of PPO was assessed in silico and the unstructured loop near the binding pocket was investigated. The substrate, intermediates, and product were docked in the catalytic domain of PPO using a modified Autodock method, introducing flexibility in the macrocycles. Sixteen PPO protein sequences across phyla were aligned and analyzed with Phyre2 and ProteinPredict to study the unstructured loop from residue 204-210 in the H. sapiens structure. Docking of the substrate, intermediates, and product all resulted in negative binding energies, though the substrate had a lower energy than the others by 40%. The α-H of C10 was found to be 1.4 angstroms closer to FAD than the β-H, explaining previous reports of the reaction occurring on the meso face of the substrate. A lack of homology in sequence or length in the unstructured loop indicates a lack of function for the protein reaction. This docking study supports a reaction mechanism proposed previously whereby all hydride abstractions occur on the C10 of the tetrapyrrole followed by tautomeric rearrangement to prepare the intermediate for the next reaction.

Objective: To investigate physical therapists' knowledge, beliefs, and current practices around falls prevention in osteoarthritis (OA) care., Methods: Currently registered, practicing Australian physical therapists who care for patients with hip and/or knee OA were invited to participate in this cross-sectional study. A comprehensive online survey was used to collect data that were analyzed descriptively or using chi-square tests; free-text responses were classified into key themes for analysis., Results: Complete responses were received from 370 eligible physical therapists, with broad representation across Australian states and practice settings. Participants worked in public and private hospitals, community health centers, private practices, and aged-care facilities. The sample ranged from new graduates to experienced physical therapists (47% had practiced ≥11 years). Despite the majority having specific training or access to educational resources, physical therapists reported only moderate confidence in assessing falls risk (median 7 [interquartile range (IQR) 6-8]; range 0 [not at all confident] to 10 [extremely confident]) and delivering falls prevention care (median 7 [IQR 6-8]). While most participants asked about falls history (88%), only 39% used falls-risk screening tools, and of these, relatively few used appropriate tools. Time constraints (including competing clinical priorities) were the most frequently perceived barrier to including falls prevention activities within OA care., Conclusion: This national snapshot of contemporary OA practice has revealed clear opportunities for optimizing clinician confidence and skills to facilitate the uptake of best-practice falls prevention strategies. Improving practice in this area may yield substantial benefits to patients and the health system if more falls can be prevented., (© 2019, American College of Rheumatology.)

Background Pulmonary imaging of chronic obstructive pulmonary disease (COPD) has focused on CT or MRI measurements, but these have not been evaluated in combination. Purpose To generate multiparametric response map (mPRM) measurements in ex-smokers with or without COPD by using volume-matched CT and hyperpolarized helium 3 ( 3 He) MRI. Materials and Methods In this prospective study ( https://clinicaltrials.gov , NCT02279329), participants underwent MRI and CT and completed pulmonary function tests, questionnaires, and the 6-minute walk test between December 2010 and January 2019. Disease status was determined by using Global initiative for chronic Obstructive Lung Disease (GOLD) criteria. The mPRM voxel values were generated by using co-registered MRI and CT labels. Kruskal-Wallis and Bonferroni tests were used to determine differences across disease severity, and correlations were determined by using Spearman coefficients. Results A total of 175 ex-smokers (mean age, 69 years ± 9 [standard deviation], 108 men) with or without COPD were evaluated. Ex-smokers without COPD had a larger fraction of normal mPRM voxels (60% vs 37%, 20%, and 7% for GOLD I, II, and III/IV disease, respectively; all P ≤ .001) and a smaller fraction of abnormal voxels, including small airways disease (normal CT, not ventilated: 5% vs 6% [not significant], 11%, and 19% [ P ≤ .001 for both] for GOLD I, II, and III/IV disease, respectively) and mild emphysema (normal CT, abnormal apparent diffusion coefficient [ADC]: 33% vs 54%, 56%, and 54% for GOLD I, II, and III/IV disease respectively; all P ≤ .001). Normal mPRM measurements were positively correlated with forced expiratory volume in 1 second (FEV 1 ) ( r = 0.65, P < .001), the FEV 1 -to-forced vital capacity ratio ( r = 0.81, P < .001), and diffusing capacity ( r = 0.75, P < .001) and were negatively correlated with worse quality of life ( r = -0.48, P < .001). Abnormal mPRM measurements of small airways disease (normal CT, not ventilated) and mild emphysema (normal CT, abnormal ADC) were negatively correlated with FEV 1 ( r = -0.65 and -0.42, respectively; P < .001) and diffusing capacity ( r = -0.53 and -0.60, respectively; P < .001) and were positively correlated with worse quality of life ( r = 0.45 and r = 0.33, respectively; P < .001), both of which were present in ex-smokers without COPD. Conclusion Multiparametric response maps revealed two abnormal structure-function results related to emphysema and small airways disease, both of which were unexpectedly present in ex-smokers with normal spirometry and CT findings. © RSNA, 2020 Online supplemental material is available for this article.

Background: Falls are a major cause of injury and death among older people. Evidence suggests that people with osteoarthritis (OA) are at a higher risk of falls and fall-related injuries including fractures. While studies demonstrate a link between OA and falls, little is known about the pathways that link falls with demographic factors, OA impairments, activity limitations and participation restrictions. The aim of this study was to identify risk factors for falls and fractures among people with OA or at high risk of developing OA using the International Classification of Functioning, Disability and Health (ICF) framework., Methods: A longitudinal analysis of data from the Osteoarthritis Initiative (OAI) dataset was undertaken. Participants were considered to have OA if they reported they had been diagnosed with knee or hip OA by a medical practitioner. Outcomes were self-reported falls and fractures. Potential predictors were classified using the ICF framework. Poisson regression models were used to determine the risk factors for falls and fractures., Results: Of the 4796 participants, 2270 (47%) were diagnosed with knee and/or hip OA. A higher proportion of participants with OA reported having had falls (72% vs 63%; p < 0.0001) and fractures (17% vs 14%; p = 0.012) than those without OA. Personal factors were found to be stronger predictors of falls and fractures compared to OA impairments, activity limitations and participation restrictions in this sample of participants. After adjusting for potential covariates, self-reported history of falls was a significant predictor of both increased falls (incidence rate ratio [IRR] 1.50; 95% confidence interval [CI] 1.40, 4.60) and fracture risk (IRR 1.38; 95% CI 1.13, 1.69)., Conclusions: By applying the ICF framework, we have shown that personal factors were more likely to predict falls and fractures rather than OA impairments, environmental factors, activity limitations and participation restrictions in people with OA or at high risk of developing OA. This highlights the importance of questioning patients about their previous falls and past medical history, and using this information to focus our assessment and clinical decision-making processes.

Objectives: This review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin., Methods: We conducted a systematic review and exploratory meta-analysis of observational studies. Electronic searches of MEDLINE and Embase, and a manual search of bibliographies was undertaken for studies published to 28 March 2018. Studies were included if: participants were men or women aged ≥18 years; the exposure of interest was aspirin; and relative risks, ORs and 95% CIs for the risk of fracture or difference (percentage or absolute) in BMD (measured by dual energy X-ray absorptiometry) between aspirin users and non-users were presented. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists for observational studies. Pooled ORs for any fracture and standardised mean differences (SMDs) for BMD outcomes were calculated using random-effects models., Results: Twelve studies met the inclusion criteria and were included in the meta-analysis. Aspirin use was associated with a 17% lower odds for any fracture (OR 0.83, 95% CI 0.70 to 0.99; I 2 =71%; six studies; n=511 390). Aspirin was associated with a higher total hip BMD for women (SMD 0.03, 95% CI -0.02 to 0.07; I 2 =0%; three studies; n=9686) and men (SMD 0.06, 95% CI -0.02 to 0.13, I 2 =0%; two studies; n=4137) although these associations were not significant. Similar results were observed for lumbar spine BMD in women (SMD 0.03, 95% CI -0.03 to 0.09; I 2 =34%; four studies; n=11 330) and men (SMD 0.08; 95% CI -0.01 to 0.18; one study; n=432)., Conclusions: While the benefits of reduced fracture risk and higher BMD from aspirin use may be modest for individuals, if confirmed in prospective controlled trials, they may confer a large population benefit given the common use of aspirin in older people., Competing Interests: Competing interests: ALB, KS, JP, SK, PE, SAW, RGC, ES and JJM are the members of the investigator group for the ASPREE-Fracture substudy., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine whether multifactorial falls prevention interventions are effective in preventing falls, fall injuries, emergency department (ED) re-presentations and hospital admissions in older adults presenting to the ED with a fall., Design: Systematic review and meta-analyses of randomised controlled trials (RCTs)., Data Sources: Four health-related electronic databases (Ovid MEDLINE, CINAHL, EMBASE, PEDro and The Cochrane Central Register of Controlled Trials) were searched (inception to June 2018)., Study Selection: RCTs of multifactorial falls prevention interventions targeting community-dwelling older adults ( ≥ 60 years) presenting to the ED with a fall with quantitative data on at least one review outcome., Data Extraction: Two independent reviewers determined inclusion, assessed study quality and undertook data extraction, discrepancies resolved by a third., Data Synthesis: 12 studies involving 3986 participants, from six countries, were eligible for inclusion. Studies were of variable methodological quality. Multifactorial interventions were heterogeneous, though the majority included education, referral to healthcare services, home modifications, exercise and medication changes. Meta-analyses demonstrated no reduction in falls (rate ratio = 0.78; 95% CI: 0.58 to 1.05), number of fallers (risk ratio = 1.02; 95% CI: 0.88 to 1.18), rate of fractured neck of femur (risk ratio = 0.82; 95% CI: 0.53 to 1.25), fall-related ED presentations (rate ratio = 0.99; 95% CI: 0.84 to 1.16) or hospitalisations (rate ratio = 1.14; 95% CI: 0.69 to 1.89) with multifactorial falls prevention programmes., Conclusions: There is insufficient evidence to support the use of multifactorial interventions to prevent falls or hospital utilisation in older people presenting to ED following a fall. Further research targeting this population group is required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: RESPOND is a telephone-based falls prevention program for older people who present to a hospital emergency department (ED) with a fall. A randomised controlled trial (RCT) found RESPOND to be effective at reducing the rate of falls and fractures, compared with usual care, but not fall injuries or hospitalisations. This process evaluation aimed to determine whether RESPOND was implemented as planned, and identify implementation barriers and facilitators., Methods: A mixed-methods evaluation was conducted alongside the RCT. Evaluation participants were the RESPOND intervention group (n = 263) and the clinicians delivering RESPOND (n = 7). Evaluation data were collected from participant recruitment and intervention records, hospital administrative records, audio-recordings of intervention sessions, and participant questionnaires. The Rochester Participatory Decision-Making Scale (RPAD) was used to evaluate person-centredness (score range 0 (worst) - 9 (best)). Process factors were compared with pre-specified criteria to determine implementation fidelity. Six focus groups were held with participants (n = 41), and interviews were conducted with RESPOND clinicians (n = 6). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the 'Capability, Opportunity, Motivation - Behaviour' (COM-B) behaviour change framework., Results: RESPOND was implemented at a lower dose than the planned 10 h over 6 months, with a median (IQR) of 2.9 h (2.1, 4). The majority (76%) of participants received their first intervention session within 1 month of hospital discharge with a median (IQR) of 18 (12, 30) days. Clinicians delivered the program in a person-centred manner with a median (IQR) RPAD score of 7 (6.5, 7.5) and 87% of questionnaire respondents were satisfied with the program. The reports from participants and clinicians suggested that implementation was facilitated by the use of positive and personally relevant health messages. Complex health and social issues were the main barriers to implementation., Conclusions: RESPOND was person-centred and reduced falls and fractures at a substantially lower dose, using fewer resources, than anticipated. However, the low dose delivered may account for the lack of effect on falls injuries and hospitalisations. The results from this evaluation provide detailed information to guide future implementation of RESPOND or similar programs., Trial Registration: This study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000336684 (27 March 2014).

Introduction: Measuring patient reported outcomes can improve the quality and effectiveness of healthcare interventions. The aim of this study was to identify the final set of items that can be included in a patient-reported outcome measure to assess recovery of patients following percutaneous coronary interventions., Methods: A consecutive sample of 200 patients registered in the Victorian Cardiac Outcomes Registry participated in a telephone survey 30 days following their percutaneous cardiac procedure. Rasch analysis was used to select the best set of items to form a concise and psychometrically sound patient-reported outcome measure. Key measurement properties assessed included overall fit to the Rasch measurement model, unidimensionality, response formats (thresholds), targeting, internal consistency and measurement invariance., Results: Five items were identified as being reliable and valid measures of patient-reported outcomes: pain or discomfort, shortness of breath, confidence in performing usual activities, feeling unhappy and having trouble sleeping. Data showed overall fit to a Rasch model of expected item functioning (χ2 16.99; p = 0.07) and all items demonstrated unidimensionality (t-test less than 0.05 threshold value). Internal consistency was acceptable (equivalent Cronbach's α 0.65) given there are only five items, but there was a ceiling effect (mean logit score -1.24) with compromised score precision for patients with better recovery., Conclusions: We identified a succinct set of items that can be used in a patient-reported outcome measure following percutaneous coronary interventions. This patient-report outcome measure has good structural validity and acceptable internal consistency. While further psychometric evaluations are recommended, the items identified capture the patient's perspective of their recovery following a percutaneous coronary intervention., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Parkinson's disease prevalence has been associated with rurality and pesticide use in studies throughout the world. Here, Parkinson's disease (PD) medication usage was used to estimate prevalence in 79 urban and rural localities in Victoria, Australia (5.3 million people)., Methods: An ecological study design was used to determine whether PD medication usage, as a reporter of PD diagnosis, differed between 79 regions in Victoria, and whether variance in PD prevalence was associated with population demographics using multiple regression. Cluster formation probability was calculated using Monte Carlo modelling. The association between agricultural production and PD prevalence was conducted with Bonferroni-adjusted Mann-Whitney-U tests., Results: PD prevalence in Victoria was estimated to be 0.85%, which was greater in rural (1.02%) compared to urban (0.80%) locations; a difference that was abolished when corrected for demographic variables. Four of the highest prevalent regions (regardless of covariate adjustment) were clustered in northwest Victoria; a formation that was unlikely to be due to chance (P = 0.00095). These regions had increased production of pulse crops., Conclusions: PD prevalence was not associated with rurality, but associated with areas of pulse production. Pulses are plants of the fabaceae family, where many of these species secrete the PD toxin, rotenone, as a natural pesticide, which may underlie increased risk. This study is limited by the data collection method, where people who do not take PD medication for their disease, or take PD-associated medication for other diseases, may impact the estimated prevalence., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Glyphosate is a widely used herbicide in commercial crop production for both conventional and herbicide-resistant crops. Herbicide-resistant crops, like glyphosate-resistant sugar beet, are often exposed to multiple applications of glyphosate during the growing season. The fate of this herbicide in resistant crops has not been publicly documented. We investigated the fate of glyphosate and main metabolite aminomethylphosphonic acid in glyphosate-resistant sugar beet grown in northern Colorado. Glyphosate residues were measured via directed ultra-high-performance liquid chromatography tandem mass spectrometry analysis of sugar beet shoots and roots throughout the growing season, from samples collected at various steps during sugar beet processing, and from flow-through samples of greenhouse-grown beets. Sugar beet rapidly absorbed glyphosate after foliar application, and subsequently translocated the herbicide to its roots, with between 2 and 3 μg/g fresh weight measured in both tissue types within 1 week of application. However, only trace amounts of glyphosate remained in either the shoots or the roots 2 weeks after application. Analysis of irrigation flow-through in pot assays confirmed that the herbicide readily exuded out of the roots. Processing of the beets removed glyphosate and herbicide levels were below the limit of detection in the crystalline sugar final product.

Objective: To inform the development of a patient-reported outcome measure, the aim of this study was to identify which symptoms and feelings following percutaneous coronary intervention (PCI) are most important to patients., Design: Discrete-choice experiment consisting of two hypothetical scenarios of 10 symptoms and feelings (pain or discomfort; shortness of breath; concern/worry about heart problems; tiredness; confidence to do usual activities; ability to do usual activities; happiness; sleep disturbance; dizziness or light-headedness and bruising) experienced after PCI, described by three levels (never, some of the time, most of the time). Preference weights were estimated using a conditional logit model., Setting: Four Australian public hospitals that contribute to the Victorian Cardiac Outcomes Registry (VCOR) and a private insurer's claim database., Participants: 138 people aged >18 years who had undergone a PCI in the previous 6 months., Main Outcome Measures: Patient preferences via trade-offs between 10 feelings and symptoms., Results: Of the 138 individuals recruited, 129 (93%) completed all 16 choice sets. Conditional logit parameter estimates were mostly monotonic (eg, moving to worse levels for each individual symptom and feeling made the option less attractive). When comparing the magnitude of the coefficients (based on the coefficient of the worst level relative to best level in each item), feeling unhappy was the symptom or feeling that most influenced perception of a least-preferred PCI outcome (OR 0.42, 95% CI 0.34 to 0.51, p<0.0001) and the least influential was bruising (OR 0.81, 95% CI 0.67 to 0.99, p=0.04)., Conclusion: This study provides new insights into how patients value symptoms and feelings they experience following a PCI., Competing Interests: Competing interests: ALB is currently the Head of Member Health Innovation at Medibank Private Ltd., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine whether body mass index (BMI), menopausal status, and hormone therapy (HT) use modify the association between physical activity (PA) patterns throughout middle age and the incidence and prevalence of joint symptoms in women in later middle age., Methods: Data were from 6,661 participants (born 1946-1951) in the Australian Longitudinal Study on Women's Health. Surveys, with questions on joint pain and stiffness, PA, height and weight, menopausal symptoms, and HT use, were completed every 3 years from 1998 to 2010. PA patterns were defined as none or low, low or meeting guidelines, fluctuating, or meeting guidelines at all times (reference pattern). Logistic regression was used to examine the association between PA patterns and prevalent (in 2010) and cumulative incident (1998-2010) joint symptoms and effect modification by patterns in BMI, menopausal status, and HT., Results: The groups representing fluctuating PA (odds ratio [OR] 1.34 [99% confidence interval (99% CI) 1.04-1.72]) and no or low PA (OR 1.60 [99% CI 1.08-2.35]) had higher odds of incident joint symptoms than those described as meeting guidelines at all times. Stratification by BMI showed that this association was statistically significant in the obese group only. No evidence for effect modification by menopausal status or HT use was found. The findings were similar for prevalent joint symptoms., Conclusion: Maintaining at least low levels of PA throughout middle age was associated with a lower prevalence and incidence of joint symptoms later in life. This apparent protective effect of PA on joint symptoms was stronger in obese women than in under- or normal-weight women, and not related to menopause or HT status., (© 2017, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Purpose: Patient-reported outcome measures (PROMs) capture health information from the patient's perspective that can be used when weighing up benefits, risks and costs of treatment. This is important for elective procedures such as those for coronary revascularisation. Patients should be involved in the development of PROMs to accurately capture outcomes that are important for the patient. The aims of this review are to identify if patients were involved in the development of cardiovascular-specific PROMs used for assessing outcomes from elective coronary revascularisation, and to explore what methods were used to capture patient perspectives., Methods: PROMs for evaluating outcomes from elective coronary revascularisation were identified from a previous review and an updated systematic search. The studies describing the development of the PROMs were reviewed for information on patient input in their conceptual and/or item development., Results: 24 PROMs were identified from a previous review and three additional PROMs were identified from the updated search. Full texts were obtained for 26 of the 27 PROMs. The 26 studies (11 multidimensional, 15 unidimensional) were reviewed. Only nine studies reported developing PROMs using patient input. For eight PROMs, the inclusion of patient input could not be judged due to insufficient information in the full text., Conclusions: Only nine of the 26 reviewed PROMs used in elective coronary revascularisation reported involving patients in their conceptual and/or item development, while patient input was unclear for eight PROMs. These findings suggest that the patient's perspective is often overlooked or poorly described in the development of PROMs.