3T sodium-MRI as predictor of neurocognition in nondemented older adults: a cross sectional study.

Dementia is a burgeoning global problem. Novel magnetic resonance imaging (MRI) metrics beyond volumetry may bring new insight and aid clinical trial evaluation of interventions early in the Alzheimer's disease course to complement existing imaging and clinical metrics. To determine whether: (i) normalized regional sodium-MRI values (Na-SI) are better predictors of neurocognitive status than volumetry (ii) cerebral amyloid PET status improves modelling. Nondemented older adult (>60 years) volunteers of known Alzheimer's Disease Assessment Scale (ADAS-Cog11), Mini-Mental State Examination (MMSE) and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neurocognitive test scores, ApolipoproteinE (APOE) e4 +/- cerebral amyloid PET status were prospectively recruited for 3T sodium-MRI brain scans. Left and right hippocampal, entorhinal and precuneus volumes and Na-SI (using the proportional intensity scaling normalization method with field inhomogeneity and partial volume corrections) were obtained after segmentation and co-registration of 3D-T1-weighted proton images. Descriptive statistics, correlation and best-subset regression analyses were performed. In our 76 nondemented participants (mean(standard deviation) age 75(5) years; woman 47(62%); cognitively unimpaired 54/76(71%), mildly cognitively impaired 22/76(29%)), left hippocampal Na-SI, not volume, was preferentially in the best models for predicting MMSE (Odds Ratio (OR) = 0.19(Confidence Interval (CI) = 0.07,0.53), P-value = 0.001) and ADAS-Cog11 (Beta(B) = 1.2(CI = 0.28,2.1), P-value = 0.01) scores. In the entorhinal analysis, right entorhinal Na-SI, not volume, was preferentially selected in the best model for predicting ADAS-Cog11 (B = 0.94(CI = 0.11,1.8), P-value = 0.03). While right entorhinal Na-SI and volume were both selected for MMSE modelling (Na-SI OR = 0.23(CI = 0.09,0.6), P-value = 0.003; volume OR = 2.6(CI = 1.0,6.6), P-value = 0.04), independently, Na-SI explained more of the variance (Na-SI R 2 = 10.3; volume R 2 = 7.5). No imaging variable was selected in the best CERAD models. Adding cerebral amyloid status improved model fit (Akaike Information Criterion increased 2.0 for all models, P-value < 0.001-0.045). Regional Na-SI were more predictive of MMSE and ADAS-Cog11 scores in our nondemented older adult cohort than volume, hippocampal more robust than entorhinal region of interest. Positive amyloid status slightly further improved model fit.

Esophago-gastric junction findings on high resolution impedance manometry in children with esophageal atresia.

OBJECTIVES: Using high resolution impedance manometry (HRIM), this study characterized the esophago-gastric junction (EGJ) dynamics in children with esophageal atresia (EA). METHOD: Esophageal HRIM was performed in patients with EA aged less than 18 years. Objective motility patterns were analyzed, and EGJ data reported. Controls were pediatric patients without EA undergoing investigations for consideration of fundoplication surgery. RESULTS: Seventy-five patients (M:F = 43:32, median age 1 year 3 months [3 months-17 years 4 months]) completed 133 HRIM studies. The majority (64/75, 85.3%) had EA with distal tracheo-esophageal fistula. Compared with controls, liquid swallows were poorer in patients with EA, as evident by significant differences in distension pressure emptying and bolus flow time (BFT). The integrated relaxation pressure for thin liquid swallows was significantly different between EA types, as well as when comparing patients with EA with and without previous esophageal dilatations. The BFT for solid swallows was significantly different when compared with EA types. CONCLUSIONS: We have utilized HRIM in patients with EA to demonstrate abnormalities in their long-term EGJ function. These abnormalities correlate with poorer esophageal compliance and reduced esophageal peristalsis across the EGJ. Understanding the EGJ function in patients with EA will allow us to tailor long-term management to specific patients.

Prognostic indicators for survival in surgically managed small intestinal obstruction in pet rabbits: 141 presentations (2011-2021).

OBJECTIVE: To determine prognostic relevance of various patient factors and intraoperative variables associated with surgical management of small intestinal obstruction in pet rabbits. ANIMALS: 114 pet rabbits with 141 presentations of small intestinal obstruction treated surgically between June 2011 and December 2021. METHODS: In a retrospective observational study design, medical records were reviewed for rabbits with small intestinal obstruction that had undergone surgical intervention. Data were collected on variables of interest and outcome (survival to hospital discharge). Univariable and multivariable logistic regression analyses were performed to identify variables associated with survival. RESULTS: Overall survival was 75.2% (106/141). Specifically, 95.7% (22/23) of presentations involving rabbits < 25 months survived. The odds of survival on univariable modeling were significantly lower in presentations of rabbits > 72 months compared with those < 25 months (OR, 0.05; 95% CI, 0.01 to 0.40; P = .005). Rectal temperature, clinicopathologic findings, etiology of obstruction, presence of full-thickness gastrointestinal wall injury, and previous small intestinal obstruction surgery did not show significant effects on survival. In a multivariable model that controlled for plasma potassium and calculated plasma osmolarity and tonicity, the odds of survival in presentations of rabbits > 72 months were 95% lower than those < 25 months (OR, 0.05; 95% CI, 0.01 to 0.50; P = .012). CLINICAL RELEVANCE: Surgical intervention should be considered a suitable treatment option for small intestinal obstruction in rabbits < 72 months and carried a good prognosis. The most common etiology was consistent with a compressed hair pellet, and extraluminal digital manipulation into the cecum was a successful surgical technique in most presentations.

Atrial Fibrillation Catheter Ablation vs Medical Therapy and Psychological Distress: A Randomized Clinical Trial.

Importance: The impact of atrial fibrillation (AF) catheter ablation on mental health outcomes is not well understood. Objective: To determine whether AF catheter ablation is associated with greater improvements in markers of psychological distress compared with medical therapy alone. Design, Setting, and Participants: The Randomized Evaluation of the Impact of Catheter Ablation on Psychological Distress in Atrial Fibrillation (REMEDIAL) study was a randomized trial of symptomatic participants conducted in 2 AF centers in Australia between June 2018 and March 2021. Interventions: Participants were randomized to receive AF catheter ablation (n = 52) or medical therapy (n = 48). Main Outcomes and Measures: The primary outcome was Hospital Anxiety and Depression Scale (HADS) score at 12 months. Secondary outcomes included follow-up assessments of prevalence of severe psychological distress (HADS score >15), anxiety HADS score, depression HADS score, and Beck Depression Inventory-II (BDI-II) score. Arrhythmia recurrence and AF burden data were also analyzed. Results: A total of 100 participants were randomized (mean age, 59 [12] years; 31 [32%] women; 54% with paroxysmal AF). Successful pulmonary vein isolation was achieved in all participants in the ablation group. The combined HADS score was lower in the ablation group vs the medical group at 6 months (8.2 [5.4] vs 11.9 [7.2]; P = .006) and at 12 months (7.6 [5.3] vs 11.8 [8.6]; between-group difference, -4.17 [95% CI, -7.04 to -1.31]; P = .005). Similarly, the prevalence of severe psychological distress was lower in the ablation group vs the medical therapy group at 6 months (14.2% vs 34%; P = .02) and at 12 months (10.2% vs 31.9%; P = .01), as was the anxiety HADS score at 6 months (4.7 [3.2] vs 6.4 [3.9]; P = .02) and 12 months (4.5 [3.3] vs 6.6 [4.8]; P = .02); the depression HADS score at 3 months (3.7 [2.6] vs 5.2 [4.0]; P = .047), 6 months (3.4 [2.7] vs 5.5 [3.9]; P = .004), and 12 months (3.1 [2.6] vs 5.2 [3.9]; P = .004); and the BDI-II score at 6 months (7.2 [6.1] vs 11.5 [9.0]; P = .01) and 12 months (6.6 [7.2] vs 10.9 [8.2]; P = .01). The median (IQR) AF burden in the ablation group was lower than in the medical therapy group (0% [0%-3.22%] vs 15.5% [1.0%-45.9%]; P < .001). Conclusion and Relevance: In this trial of participants with symptomatic AF, improvement in psychological symptoms of anxiety and depression was observed with catheter ablation, but not medical therapy. Trial Registration: ANZCTR Identifier: ACTRN12618000062224.

WHAM-A Prospective Study of Weight and Body Composition After Risk-Reducing Bilateral Salpingo-oophorectomy.

CONTEXT: Body weight and composition may change over the natural menopause transition. Whether surgical menopause has similar effects, and the impact of hormone replacement therapy (HRT), are unknown. Understanding the metabolic effects of surgical menopause will inform clinical care. OBJECTIVE: To prospectively measure weight and body composition over 24 months following surgical menopause compared with a similar comparison group who retained their ovaries. METHODS: Prospective observational study of weight change from baseline to 24 months in 95 premenopausal women at elevated risk of ovarian cancer planning risk-reducing salpingo-oophorectomy (RRSO) and 99 comparators who retained their ovaries. Change in body composition from baseline to 24 months was also assessed by dual-energy x-ray absorptiometry in a subgroup of 54 women who underwent RRSO and 81 comparators who retained their ovaries. In the subgroup, weight, fat mass, lean mass, and abdominal fat measures were compared between groups. RESULTS: At 24 months both groups had gained weight (RRSO 2760 ± 4860 g vs comparators 1620 ± 4540 g) with no difference between groups (mean difference 730 g; 95% CI 920 g to 2380 g; P = .383). In the body composition subgroup, there was no difference in weight between groups at 24 months (mean difference 944 g; 95% CI -1120 g to 2614 g; P = .431). RRSO women may have gained slightly more abdominal visceral adipose tissue (mean difference 99.0 g; 95% CI 8.8 g to 189.2 g; P = .032) but there were no other differences in body composition. There were also no differences in weight or body composition between HRT users and nonusers at 24 months. CONCLUSION: 24 months after RRSO, there was no difference in body weight compared with women who retained their ovaries. RRSO women gained more abdominal visceral adipose tissue than comparators, but there were no other differences in body composition. Use of HRT following RRSO had no effect on these outcomes.

Impact of Catheter Ablation on Cognitive Function in Atrial Fibrillation: A Randomized Control Trial.

BACKGROUND: Early postoperative cognitive dysfunction (POCD) has been reported following atrial fibrillation (AF) ablation. However, whether POCD is persistent long-term is unknown. OBJECTIVES: The purpose of this study was to determine if AF catheter ablation is associated with persistent cognitive dysfunction at 12-month follow-up. METHODS: This is a prospective study of 100 patients with symptomatic AF who failed at least 1 antiarrhythmic drug randomized to either ongoing medical therapy or AF catheter ablation and followed up for 12 months. Changes in cognitive performance were assessed using 6 cognitive tests administered at baseline and during follow-up (3, 6, and 12 months). RESULTS: A total of 96 participants completed the study protocol. Mean age was 59 ± 12 years (32% women, 46% with persistent AF). The prevalence of new cognitive dysfunction in the ablation arm compared with the medical arm was as follows: at 3 months: 14% vs 2%; P = 0.03; at 6 months: 4% vs 2%; P = NS; and at 12 months: 0% vs 2%; P = NS. Ablation time was an independent predictor of POCD (P = 0.03). A significant improvement in cognitive scores was seen in 14% of the ablation arm patients at 12 months compared with no patients in the medical arm (P = 0.007). CONCLUSIONS: POCD was observed following AF ablation. However, this was transient with complete recovery at 12-month follow-up.

Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes. OBJECTIVES: The aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms. METHODS: Patients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up. RESULTS: A total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO2 (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg/min; P < 0.01), N-terminal pro-B-type natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± -21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization-based criteria for HFpEF vs 7% in the medical arm (P = 0.02). CONCLUSIONS: AF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF.

Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial.

Importance: Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct. However, PWI has not been subjected to randomized comparison. Objective: To compare PVI with PWI vs PVI alone in patients with persistent AF undergoing first-time catheter ablation. Design, Setting, and Participants: Investigator initiated, multicenter, randomized clinical trial involving 11 centers in 3 countries (Australia, Canada, UK). Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone. Patients were enrolled July 2018-March 2021, with 1-year follow-up completed March 2022. Interventions: The PVI with PWI group (n = 170) underwent wide antral pulmonary vein isolation followed by posterior wall isolation involving linear ablation at the roof and floor to achieve electrical isolation. The PVI-alone group (n = 168) underwent wide antral pulmonary vein isolation alone. Main Outcomes and Measures: Primary end point was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication at 12 months, after a single ablation procedure. The 23 secondary outcomes included freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures, freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications. Results: Among 338 patients randomized (median age, 65.6 [IQR, 13.1] years; 76.9% men), 330 (97.6%) completed the study. After 12 months, 89 patients (52.4%) assigned to PVI with PWI were free from recurrent atrial arrhythmia without antiarrhythmic medication after a single procedure, compared with 90 (53.6%) assigned to PVI alone (between-group difference, -1.2%; hazard ratio [HR], 0.99 [95% CI, 0.73-1.36]; P = .98). Of the secondary end points, 9 showed no significant difference, including freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures (58.2% for PVI with PWI vs 60.1% for PVI alone; HR, 1.10 [95% CI, 0.79-1.55]; P = .57), freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures (68.2% vs 72%; HR, 1.20 [95% CI, 0.80-1.78]; P = .36) or AF burden (0% [IQR, 0%-2.3%] vs 0% [IQR, 0%-2.8%], P = .47). Mean procedural times (142 [SD, 69] vs 121 [SD, 57] minutes, P < .001) and ablation times (34 [SD, 21] vs 28 [SD, 12] minutes, P < .001) were significantly shorter for PVI alone. There were 6 complications for PVI with PWI and 4 for PVI alone. Conclusions and Relevance: In patients undergoing first-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone. These findings do not support the empirical inclusion of PWI for ablation of persistent AF. Trial Registration: anzctr.org.au Identifier: ACTRN12616001436460.

Exploratory and confirmatory factor analysis of the questionnaire on Palliative Care for Advanced Dementia (qPAD) using a large sample of staff from Australian residential aged care homes.

BACKGROUND: The Questionnaire on Palliative Care for Advanced Dementia (qPAD) is increasingly being used to assess residential aged care workers' knowledge and attitudes about palliative care for people with dementia. The qPAD developers performed an exploratory factor analysis and assessed the internal consistency using a small sample. AIM: The aim of this study was to further assess the structural validity of the qPAD using a large sample of qPAD responses from staff who work in residential aged care homes in Australia. METHODS: Data from 727 care staff who participated in an Australian dementia palliative care training project were used for exploratory factor analyses, assessment of internal consistency, and confirmatory factor analysis of the knowledge test and attitude scale components of the qPAD. RESULTS: The exploratory factor analysis of the knowledge test produced a four-factor solution. One item loaded weakly, and four items had cross-loadings. Factor labels for the knowledge test were difficult to define. Factor analysis of the attitude scale produced a three-factor structure with good internal consistency-Feeling valued and part of the care team (α = 0.88), Family and team engagement (α = 0.75) and Perceptions and beliefs (α = 0.83). Confirmatory factor analysis indicated improvements in model fit were needed for both the knowledge test and attitude scale. CONCLUSION: The findings of this factor analysis differed from the original study. The attitude scale produced a three-factor structure, but the knowledge test requires further development due to weak and cross-loadings of several items, inadequate internal consistency of factors and poor model fit.

How often do cancer researchers make their data and code available and what factors are associated with sharing?

BACKGROUND: Various stakeholders are calling for increased availability of data and code from cancer research. However, it is unclear how commonly these products are shared, and what factors are associated with sharing. Our objective was to evaluate how frequently oncology researchers make data and code available and explore factors associated with sharing. METHODS: A cross-sectional analysis of a random sample of 306 cancer-related articles indexed in PubMed in 2019 which studied research subjects with a cancer diagnosis was performed. All articles were independently screened for eligibility by two authors. Outcomes of interest included the prevalence of affirmative sharing declarations and the rate with which declarations connected to data complying with key FAIR principles (e.g. posted to a recognised repository, assigned an identifier, data license outlined, non-proprietary formatting). We also investigated associations between sharing rates and several journal characteristics (e.g. sharing policies, publication models), study characteristics (e.g. cancer rarity, study design), open science practices (e.g. pre-registration, pre-printing) and subsequent citation rates between 2020 and 2021. RESULTS: One in five studies declared data were publicly available (59/306, 19%, 95% CI: 15-24%). However, when data availability was investigated this percentage dropped to 16% (49/306, 95% CI: 12-20%), and then to less than 1% (1/306, 95% CI: 0-2%) when data were checked for compliance with key FAIR principles. While only 4% of articles that used inferential statistics reported code to be available (10/274, 95% CI: 2-6%), the odds of reporting code to be available were 5.6 times higher for researchers who shared data. Compliance with mandatory data and code sharing policies was observed in 48% (14/29) and 0% (0/6) of articles, respectively. However, 88% of articles (45/51) included data availability statements when required. Policies that encouraged data sharing did not appear to be any more effective than not having a policy at all. The only factors associated with higher rates of data sharing were studying rare cancers and using publicly available data to complement original research. CONCLUSIONS: Data and code sharing in oncology occurs infrequently, and at a lower rate than would be expected given the prevalence of mandatory sharing policies. There is also a large gap between those declaring data to be available, and those archiving data in a way that facilitates its reuse. We encourage journals to actively check compliance with sharing policies, and researchers consult community-accepted guidelines when archiving the products of their research.

Catheter ablation for persistent atrial fibrillation: A multicenter randomized trial of pulmonary vein isolation (PVI) versus PVI with posterior left atrial wall isolation (PWI) - The CAPLA study.

BACKGROUND: The success of pulmonary vein isolation (PVI) is reduced in persistent AF (PsAF) compared to paroxysmal AF. Adjunctive ablation strategies have failed to show consistent incremental benefit over PVI alone in randomized studies. The left atrial posterior wall is a potential source of non-PV triggers and atrial substrate which may promote the initiation and maintenance of PsAF. Adding posterior wall isolation (PWI) to PVI had shown conflicting outcomes, with earlier studies confounded by methodological limitations. OBJECTIVES: To determine whether combining PWI with PVI significantly improves freedom from AF recurrence, compared to PVI alone, in patients with PsAF. METHODS: This is a multi-center, prospective, international randomized clinical trial. 338 patients with symptomatic PsAF refractory to anti-arrhythmic therapy (AAD) will be randomized to either PVI alone or PVI with PWI in a 1:1 ratio. PVI involves wide antral circumferential pulmonary vein (PV) isolation, utilizing contact force sensing ablation catheters. PWI involves the creation of a floor line connecting the inferior aspect of the PVs, and a roof line connecting the superior aspect of the PVs. Follow up is for a minimum of 12 months with rhythm monitoring via implantable cardiac device and/or loop monitor, or frequent intermittent monitoring with an ECG device. The primary outcome is freedom from any documented atrial arrhythmia of > 30 seconds off AAD at 12 months, after a single ablation procedure. CONCLUSIONS: This randomized study aims to determine the success and safety of adjunctive PWI to PVI in patients with persistent AF.

Glucose patterns following alcohol and illicit drug use in young adults with type 1 diabetes: A flash glucose monitoring study.

INTRODUCTION: To assess the effects of alcohol and illicit drug use in young adults (age 18-35) with type 1 diabetes (T1D) on flash glucose monitor sensor glucose (SG) readings. METHODS: Twenty young adults with T1D were enrolled from a tertiary referral hospital outpatient department in Melbourne, Australia for a 6-week prospective observational study using flash glucose monitoring (FGM). Glucometrics comparing substance using days (SUEDs) to those without substance use (non-SUEDS) were analysed. The primary outcomes were the difference in mean SG values, its standard deviation and minutes/24-h period out of range (SG <3.9 mmol/L or >10.0 mmol/L) between matched SUEDs vs non-SUEDs. An interaction model with the primary effect of HbA1c on SG values was also performed. RESULTS: There were no differences in the primary outcome measures between SUEDS and non-SUEDs. However, there were differences in the regression coefficients for HbA1c and glucometrics between non-SUEDs and SUEDs for mean SG, time out of range and time with SG > 10 mmol/L. This difference was also identified between non-SUEDS and days of ≥40 g alcohol for mean SG. CONCLUSIONS: While there was no difference between glucometrics for SUEDs and non-SUEDs on primary outcomes, HbA1C was found to be a less reliable predictor of glucose patterns in the 24-h period following substance use than control days. Young adults with T1D need to monitor and respond to their glucose levels following substance use and engage in harm minimisation practices irrespective of baseline glucose control.

Interpretation of clinical studies in electrophysiology: statistical considerations for the clinician.

Atrial fibrillation (AF) outcome studies play an essential role in the development of clinical evidence to improve the management of AF patients. Understanding the statistical considerations involved in study design and interpretation is crucial if electrophysiologists are to change practice. In this review, with the guidance of a medical statistician and a clinical trialist we provide an overview of important statistical issues for the clinician, with a focus on clinical studies in AF ablation. Various types of study designs including randomized controlled trials, superiority, and non-inferiority studies are described, along with their implications and limitations. Appropriate sample size calculation is fundamental to ensure statistical power and efficient resource use. Multiplicity in study endpoints is useful to encapsulate the varied effects of an intervention/treatment, although statistical adjustments are required to account for this. Finally, we discuss the limitations with the current primary endpoint used in AF ablation studies, namely, freedom from atrial tachyarrhythmia of >30 seconds, and propose AF burden as a more relevant primary endpoint, based on findings from recent clinical studies. However, technical challenges need to be overcome before AF burden can be routinely adopted, especially the need for non-invasive, long-term monitoring. The emergence of newer technologies, particularly wearable technology, offers significant promise in filling this gap.

Funding of prostate magnetic resonance imaging leads to fewer biopsies and potential savings to health systems in the management of prostate cancer.

OBJECTIVES: To assess the impact of the introduction of multiparametric magnetic resonance imaging of the prostate (mpMRIp) on the number of prostate biopsies performed in Australia. METHODS: Australian Medicare published statistics from 1 July 2007 to 30 June 2019 were obtained from publically available databases for prostate-specific antigen (PSA) testing, prostate biopsy, and mpMRIp. Analysis was divided into three time periods broadly based on availability of mpMRI to the Australian public: 2007-2012 (no mpMRIp), 2012-2018 (mpMRIp available, privately funded), and 2018-2019 (mpMRIp available with Medicare funding). Introduction of mpMRIp was hypothesised to reduce the number of prostate biopsies performed. PSA testing numbers were used as a control. The economics model, proposed by the Medical Services Advisory Committee (MSAC), was analysed for cost savings. RESULTS: Accounting for variations in PSA testing, the introduction of mpMRIp from 2012 coincided with a reduction in the number of prostate biopsies by an average of 354.7/month (95% CI 175, 534.4; P < 0.001). Whilst the number of mpMRIp performed for the initial 12 months was underestimated by the MSAC at 38 470 vs 20 149 (+$8.3 million Australian dollars), we estimate the annual savings from reduced number biopsies and biopsy-associated complications to be $13.2 ± 9.6 million. CONCLUSION: Availability of mpMRIp in Australia has correlated with a significant reduction in prostate biopsy rates, with an estimated annual saving of $13.2 ± 9.6 million. Government funding of this diagnostic service has the potential to improve health equity and save on health expenditure.

Assessment of serum symmetric dimethylarginine and creatinine concentrations in hyperthyroid cats before and after a fixed dose of orally administered radioiodine.

BACKGROUND: Serum symmetric dimethylarginine (SDMA) is a sensitive renal biomarker for detecting early chronic kidney disease (CKD) in nonhyperthyroid cats, but knowledge regarding its performance in hyperthyroid cats remains limited. OBJECTIVES: To determine the relationship between serum SDMA, creatinine and total thyroxine (TT4) concentrations in hyperthyroid cats before (T0) and 3 months after (T1) receiving a PO fixed dose of radioiodine. ANIMALS: Eighty client-owned hyperthyroid cats. METHODS: Prospective cohort study. Serum TT4, and SDMA, creatinine concentrations, and urine specific gravity were measured at T0 and T1. Nonparametric tests were used to determine the relationship among SDMA, and creatinine and TT4 concentrations. Agreement between SDMA and creatinine regarding CKD staging at both time points was assessed using Goodman and Kruskal's gamma statistic. RESULTS: Mean serum SDMA concentration increased after treatment of hyperthyroidism. However, 21 of 75 cats experienced a decrease in SDMA between T0 and T1, whereas creatinine decreased in only 2 cats. A moderate correlation between SDMA and creatinine was seen at T1 (r = 0.53; P < .001) but not at T0 (r = 0.13; P = .25). Where assessable at T1, poor agreement was observed between SDMA and creatinine and CKD stage (Goodman and Kruskal's gamma 0.20; P = .29). CONCLUSIONS AND CLINICAL IMPORTANCE: Discordant outcomes between SDMA and creatinine after radioiodine treatment in cats with hyperthyroidism suggest extrarenal factors may interfere with the reliability of SDMA to adequately reflect renal function. As a result, SDMA should not be interpreted in isolation in hyperthyroid cats treated with radioiodine.

The Adaptation to Mandarin-Accented English by Older, Hearing-Impaired Listeners Following Brief Exposure to the Accent.

Purpose The language processing of Mandarin-accented English (MAE) by older hearing-impaired (OHI), older normally hearing (NH), and younger NH listeners was explored. We examined whether OHI adults have more difficulty than NH listeners in recognizing and adapting to MAE speech productions after receiving brief training with the accent. Method Talker-independent adaptation was evaluated in an exposure training study design. Listeners were trained either by four MAE talkers or four Australian English talkers (control group) before listening to sentences presented by a novel MAE talker. Speech recognition for both the training sentences and the experimental sentences were compared between listener groups and between the training accents. Results Listeners in all three groups (OHI, older NH, younger NH) who had been trained by the MAE talkers showed higher odds of speech recognition than listeners trained by the Australian English talkers. The OHI listeners adapted to MAE to the same degree as the NH groups despite returning lower overall odds of recognizing MAE speech. Conclusions Older listeners with mild-to-moderate hearing loss were able to benefit as much from brief exposure to MAE as did the NH groups. This encouraging result suggests that OHI listeners have access to and can exploit the information present in a relatively brief sample of accented speech and generalize their learning to a novel MAE talker.

Practitioners' perceptions of the ASQ-TRAK developmental screening tool for use in Aboriginal children: A preliminary survey.

AIM: To determine health practitioners' experience of using the culturally adapted Ages and Stages Questionnaire - Talking about Raising Aboriginal Kids (ASQ-TRAK) and the Ages and Stages Questionnaire-3 (ASQ-3) with Australian Aboriginal families and their perception about parents' acceptability and understanding of the instruments. METHODS: We surveyed a convenience sample of practitioners who had used both the ASQ-TRAK and the ASQ-3 developmental screening tools with Aboriginal children in the Northern Territory and South Australia. We compared their experience and perception about parents' acceptability and understanding of both instruments. RESULTS: All 38 respondents used the ASQ-3 and 35 the ASQ-TRAK; 100% rated the ASQ-TRAK as more acceptable and easier to understand for parents compared with 68% (P < 0.001) and 52.6% (P < 0.001), respectively, for the ASQ-3. A greater proportion of respondents were satisfied using the ASQ-TRAK (100%) than the ASQ-3 (65.7%) (P = 0.003). A higher proportion indicated that the ASQ-TRAK was respectful (85.3% compared with ASQ-3 27.8%, P < 0.001), culturally relevant (70.6% compared to 16.2%, P < 0.001) and engaging (76.5% compared to 16.2%, P < 0.001). Qualitative exploration of respondents' comments supported the quantitative findings. The ASQ-TRAK was considered more culturally appropriate, engaging and useful. CONCLUSIONS: Our findings demonstrate that the culturally adapted ASQ-TRAK is preferred to the ASQ-3 by health practitioners in the Australian Aboriginal context. Failing to address cultural and linguistic factors and applying measurement tools developed for one population to another, is problematic in any setting. While further research is required to explore parents' experience directly, these data provide support for the ASQ-TRAK to be used in this context.

Assessment of treatment outcomes in hyperthyroid cats treated with an orally administered fixed dose of radioiodine.

OBJECTIVES: The aims of this study were to describe the treatment outcomes following oral administration of a fixed dose (138 MBq; 3.7 mCi) of radioiodine in hyperthyroid cats and to examine the correlation between total thyroxine (TT4) concentrations before and after treatment. METHODS: This was a retrospective cohort study that documented the TT4 concentration and clinicopathological parameters at the time of diagnosis and after treatment. Logistic regression was used to assess the relationship between TT4 concentrations before and after treatment. The difference in pre- and post-treatment variables between cats that had TT4 concentrations below or within the reference interval (RI) was compared by the Mann-Whitney U-test. RESULTS: Of 161 cats, 133 (82.6%) cats had TT4 concentrations within the RI, four (2.5%) cats had TT4 concentrations above the RI and 24 (14.9%) cats had TT4 concentrations below the RI after treatment. The severity of hyperthyroidism at diagnosis, as measured by the percentage of TT4 elevation above the upper limit of the RI, had no impact on the odds of cats having low TT4 concentrations after treatment (odds ratio 1.00; 95% confidence interval 0.96-1.05; P = 0.828). CONCLUSIONS AND RELEVANCE: When using an orally administered fixed dose of radioiodine for the treatment of feline hyperthyroidism, TT4 concentrations at diagnosis cannot be used to predict TT4 concentrations after treatment. The proportion of cats with TT4 concentrations below the lower limit of the RI after treatment was 14.9%. Further work is required to optimise oral radioiodine dosing to achieve maximal euthyroid outcomes.

Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices.

Stem cells have been touted as a source of potential replacement neurons for inner ear degeneration for almost two decades now; yet to date, there are few studies describing the use of human pluripotent stem cells (hPSCs) for this purpose. If stem cell therapies are to be used clinically, it is critical to validate the usefulness of hPSC lines in vitro and in vivo. Here, we present the first quantitative evidence that differentiated hPSC-derived neurons that innervate both the inner ear hair cells and cochlear nucleus neurons in coculture, with significantly more new synaptic contacts formed on target cell types. Nascent contacts between stem cells and hair cells were immunopositive for both synapsin I and VGLUT1, closely resembling expression of these puncta in endogenous postnatal auditory neurons and control cocultures. When hPSCs were cocultured with cochlear nucleus brainstem slice, significantly greater numbers of VGLUT1 puncta were observed in comparison to slice alone. New VGLUT1 puncta in cocultures with cochlear nucleus slice were not significantly different in size, only in quantity. This experimentation describes new coculture models for assessing auditory regeneration using well-characterised hPSC-derived neurons and highlights useful methods to quantify the extent of innervation on different cell types in the inner ear and brainstem.

The effect of physiological state, milk production traits and environmental conditions on milk fat globule size in cow's milk.

This research was carried out to quantify the effects of a range of variables on milk fat globule (MFG) size for a herd of Holstein-Friesian cows managed through an automatic milking system with year-round calving. We hypothesised that the overall variation in average MFG size observed between individual animals of the same herd cannot sufficiently be explained by the magnitude of the effects of variables that could be manipulated on-farm. Hence, we aimed to conduct an extensive analysis of possible determinants of MFG size, including physiological characteristics (parity, days in milk, days pregnant, weight, age, rumination minutes, somatic cell count) and milk production traits (number of milkings, milk yield, fat yield, protein and fat content, fat-protein ratio) on the individual animal level; and environmental conditions (diet, weather, season) for the whole herd. Our results show that when analysed in isolation, many of the studied variables have a detectable effect on MFG size. However, analysis of their additive effects identified days in milk, parity and milk yield as the most important variables. In accordance with our hypothesis, the estimated effects of these variables, calculated using a multiple variable linear mixed model, do not sufficiently explain the overall variation between cows, ranging from 2.70 to 5.69 µm in average MFG size. We further show that environmental variables, such as sampling day (across seasons) or the proportion of pasture and silage in the diet, have limited effects on MFG size and that physiological differences outweigh the effects of milk production traits and environmental conditions. This presents further evidence that the selection of individual animals is more important than the adjustment of on-farm variables to control MFG size.