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Objectives: The 4-m gait speed (4mGS) and 10-m gait speed (10mGS) tests and the 30-second sit-to-stand (30sSTS) and 5-times sit-to-stand (5xSTS) tests are commonly used and advocated in consensus recommendations. We compared these tests on their predictive and clinical value concerning the risk of prefrailty/frailty and restricted life-space mobility (RLSM)., Design: Cross-sectional study., Setting and Participants: A sample of 1235 community-dwelling adults (mean ± SD, 68 ± 7 years) participated in this prospective cohort study., Methods: At baseline assessment, participants completed a survey and functional assessment, from which gait speed, sit-to-stand performance, self-reported mobility limitation, 40-item Frailty Index, and Life Space Assessment were measured. Participants with a 40-item Frailty Index >0.15 and a Life Space Assessment <60 points were classified as having prefrailty/frailty and RLSM, respectively. At 1-year follow-up assessment, prefrailty/frailty and RLSM were evaluated., Results: Correlations between gait speed and sit-to-stand measures were high (ρ values >0.80). In multivariable ordinal models, these measures added incremental prognostic value beyond a base model comprising demographics and self-reported mobility limitation variables in predicting baseline and 1-year outcomes. Between 10mGS and 4mGS, models with 10mGS had higher concordance indices (differences, 0.005-0.009), and these differences translated to generally greater net benefit in decision curve analyses. Between 30sSTS and 5xSTS measures, no one measure consistently outperformed the other, with small net benefit differences between measures (<0.2%)., Conclusions and Implications: In community-dwelling older adults, gait speed and sit-to-stand measures meaningfully predicted prefrailty/frailty and RLSM. 10mGS provided more robust prognostic information than the 4mGS, whereas 5xSTS and 30sSTS measures showed near equivalence of performance. These findings could guide the choice of functional measures in clinical and research settings., Competing Interests: Disclosure Y.-H. Pua and R. A. Clark are involved in a provisional patent application for a gait speed assessment device. This device is not used in this study. The other authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Management of aortic stenosis (AS) in patients with chronic kidney disease (CKD) may often be overlooked, and this could confer poorer outcomes., Methods: Consecutive patients ( n = 727) with index echocardiographic diagnosis of moderate to severe AS (aortic valve area <1.5 cm 2 ) were examined. They were divided into those with CKD (estimated glomerular filtration rate < 60 mL/min) and those without. Baseline clinical and echocardiographic parameters were compared, and a multivariate Cox regression model was constructed. Clinical outcomes were compared using Kaplan-Meier curves., Results: There were 270 (37.1%) patients with concomitant CKD. The CKD group was older (78.0 ± 10.3 vs. 72.1 ± 12.9 years, P < 0.001), with a higher prevalence of hypertension, diabetes mellitus, hyperlipidaemia and ischaemic heart disease. AS severity did not differ significantly, but left ventricular (LV) mass index (119.4 ± 43.7 vs. 112.3 ± 40.6 g/m 2 , P = 0.027) and Doppler mitral inflow E to annular tissue Doppler e' ratio (E: e' 21.5 ± 14.6 vs. 17.8 ± 12.2, P = 0.001) were higher in the CKD group. There was higher mortality (log-rank 51.5, P < 0.001) and more frequent admissions for cardiac failure (log-rank 25.9, P < 0.001) in the CKD group, with a lower incidence of aortic valve replacement (log-rank 7.12, P = 0.008). On multivariate analyses, after adjusting for aortic valve area, age, left ventricular ejection fraction and clinical comorbidities, CKD remained independently associated with mortality (hazard ratio 1.96, 95% confidence interval 1.50-2.57, P < 0.001)., Conclusion: Concomitant CKD in patients with moderate to severe AS was associated with increased mortality, more frequent admissions for cardiac failure and a lower incidence of aortic valve replacement., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Background: Echocardiographic indexes of aortic stenosis may not comprehensively reflect disease morbidity. Plasma proteomic profiling may add prognostic value in these patients., Methods and Results: Proximity extension assays (Olink) of 183 circulating cardiovascular and inflammatory proteins were performed in a prospective follow-up study of 122 asymptomatic/minimally symptomatic patients (mean±SD age, 69.1±10.9 years; 61% men) with moderate to severe aortic stenosis and preserved left ventricular ejection fraction. Protein signatures of higher-risk echocardiographic subgroups were determined. Associations of proteins with the primary composite outcome (heart failure hospitalization, progression to New York Heart Association class III-IV, or all-cause mortality) were evaluated using competing risk analyses, with aortic valve replacement being the competing risk. Network analysis unveiled mutually exclusive communities of proteins and echocardiographic parameters, connected only through NT-proBNP (N-terminal pro-B-type natriuretic peptide). Members of the tumor necrosis factor receptor superfamily (TNFRSF1A, TNFRSF1B, and TNFRSF14), and trefoil factor-3 were major hub proteins among the circulating biomarkers. Left ventricular global longitudinal strain >-15% was associated with higher levels of proteins, primarily of inflammation and immune regulation, whereas aortic valve area <1 cm 2 , E/e' >15, and left atrial reservoir strain <20% were associated with higher levels of NT-proBNP. Of 14 proteins associated with the primary end point, phospholipase-C, C-X-C motif chemokine-9, and interleukin-10 receptor subunit β demonstrated the highest hazard ratios after adjusting for clinical factors ( q <0.05)., Conclusions: Plasma proteins involved in inflammation and immune regulation were differentially expressed in patients with aortic stenosis with reduced left ventricular global longitudinal strain, and associated with adverse clinical outcomes. Their incorporation into aortic stenosis risk stratification warrants further assessment.

Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017-2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans.

Aim: This study aimed to investigate the association between intrinsic capacity (IC) and frailty in community-dwelling older adults. Specifically, we examined the utility of the World Health Organization's Integrated Care for Older People Step 1 screen for identifying frail older persons in the community., Methods: This is a cross-sectional analysis of a community frailty screening initiative. IC loss was ascertained using the World Health Organization's Integrated Care for Older People Step 1 questions. The Clinical Frailty Scale was used to categorize participants as robust (Clinical Frailty Scale S1-3) or frail (Clinical Frailty Scale ≥4). Logistic regression was used to analyze the association of individual and cumulative IC losses with frailty, adjusting for confounders. Additionally, the diagnostic performance of using cumulative IC losses to identify frailty was assessed., Results: This study included 1164 participants (28.2% frail). Loss in locomotion (adjusted odds ratio [AOR] 1.47, 95% CI 1.07-2.02), vitality (AOR 1.58, 95% CI 1.04-2.39), sensory (AOR 1.99, 95% CI 1.51-2.64) and psychological capacities (AOR 1.92, 95% CI 1.45-2.56) were significantly associated with frailty. Loss in more than three IC domains was associated with frailty. Using loss in at least three ICs identifies frailty, with sensitivity of 38.6%, specificity of 83.5% and positive predictive value of 47.4%. Using loss in at least four ICs improved specificity to 96.9%, and is associated with the highest positive predictive value of 57.6% and highest positive likelihood ratio of 3.55 for frailty among all cut-off values. The area under the receiver operating characteristic curve was 0.64 (95% CI 0.61-0.68)., Conclusions: IC loss as identified through World Health Organization's Integrated Care for Older People Step 1 is associated with frailty community-dwelling older adults. Geriatr Gerontol Int 2024; 24: 457-463., (© 2024 Japan Geriatrics Society.)

Background: Although the frailty index (FI) is designed as a continuous measure of frailty, thresholds are often needed to guide its interpretation. This study aimed to introduce and demonstrate the utility of an item response theory (IRT) method in estimating FI interpretation thresholds in community-dwelling adults and to compare them with cutoffs estimated using the receiver operating characteristics (ROC) method., Methods: A sample of 1,149 community-dwelling adults (mean[SD], 68[7] years) participated in this cross-sectional study. Participants completed a multi-domain geriatric screen from which the 40-item FI and 3 clinical anchors were computed - namely, (i)self-reported mobility limitations (SRML), (ii)"fair" or "poor" self-rated health (SRH), and (iii) restricted life-space mobility (RLSM). Participants were classified as having SRML-1 if they responded "Yes" to either of the 2 questions regarding walking and stair climbing difficulty and SRML-2 if they reported having walking and stair climbing difficulty. Participants with a Life Space Assessment score <60 points were classified as having RLSM. Threshold values for all anchor questions were estimated using the IRT method and ROC analysis with Youden criterion., Results: The proportions of participants with SRML-1, SRML-2, Fair/Poor SRH, and RLSM were 21 %, 8 %, 22 %, and 9 %, respectively. The IRT-based thresholds for SRML-2 (0.26), fair/poor SRH (0.29), and RLSM (0.32) were significantly higher than those for SRML-1 (0.18). ROC-based FI cutoffs were significantly lower than IRT-based values for SRML-2, SRH, and RLSM (0.12 to 0.17), and they varied minimally and non-systematically across the anchors., Conclusions: The IRT method identifies biologically plausible FI thresholds that could meaningfully complement and contextualize existing thresholds for defining frailty., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Buruli ulcer, a chronic subcutaneous infection caused by Mycobacterium ulcerans, is increasing in prevalence in southeastern Australia. Possums are a local wildlife reservoir for M. ulcerans and, although mosquitoes have been implicated in transmission, it remains unclear how humans acquire infection. We conducted extensive field survey analyses of M. ulcerans prevalence among mosquitoes in the Mornington Peninsula region of southeastern Australia. PCR screening of trapped mosquitoes revealed a significant association between M. ulcerans and Aedes notoscriptus. Spatial scanning statistics revealed overlap between clusters of M. ulcerans-positive Ae. notoscriptus, M. ulcerans-positive possum excreta and Buruli ulcer cases, and metabarcoding analyses showed individual mosquitoes had fed on humans and possums. Bacterial genomic analysis confirmed shared single-nucleotide-polymorphism profiles for M. ulcerans detected in mosquitoes, possum excreta and humans. These findings indicate Ae. notoscriptus probably transmit M. ulcerans in southeastern Australia and highlight mosquito control as a Buruli ulcer prevention measure., (© 2024. The Author(s).)

Objectives: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance., Methods: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context., Results: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs., Conclusion: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.

Objectives: Clinical interpretability of the gait speed and 5-times sit-to-stand (5-STS) tests is commonly established by comparing older adults with and without self-reported mobility limitations (SRML) on gait speed and 5-STS performance, and estimating clinical cutpoints for SRML using the receiver operating characteristics (ROC) method. Accumulating evidence, however, suggests that the adjusted predictive modeling (APM) method may be more appropriate to estimate these interpretational cutpoints. Thus, we aimed to compare, in community-dwelling older adults, gait speed and 5-STS cutpoints estimated using the ROC and APM methods., Design: Cross-sectional study., Setting and Participants: This study analyzed data from 955 community-dwelling independently walking older adults (73%women) aged ≥60 years (mean, 68; range, 60-88)., Methods: Participants completed the 10-metre gait speed and 5-STS tests. Participants were classified as having SRML if they responded "Yes" to either of the 2 questions regarding walking and stair climbing difficulty. Cutpoints for SRML and its component questions were estimated using ROC analysis with Youden criterion and the APM method., Results: The proportions of participants with self-reported walking difficulty, self-reported stair climbing difficulty, and SRML were 10%, 19%, and 22%, respectively. Gait speed and 5-STS time were moderately correlated with each other (r=-0.56) and with the self-reported measures (absolute r-values, 0.39-0.44). ROC-based gait speed cutpoints were 0.14 to 0.16 m/s greater than APM-based cutpoints (P < 0.05) whilst ROC-based 5-STS time cutpoints were 0.8 to 3.3 s lower than APM-based cutpoints (P < 0.05 for walking difficulty). Compared with ROC-based cutpoints, APM-based cutptoints were more precise and they varied monotonically with self-reported walking difficulty, self-reported stair climbing difficulty, and SRML., Conclusions and Implications: In a sample of 955 older adults, our findings of precise and biologically plausible gait speed and 5-STS cutpoints for SRML estimated using the APM method indicate that this promising method could potentially complement or even replace traditional ROC methods., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Buruli ulcer (BU) is a neglected tropical disease caused by infection of subcutaneous tissue with Mycobacterium ulcerans . BU is commonly reported across rural regions of Central and West Africa but has been increasing dramatically in temperate southeast Australia around the major metropolitan city of Melbourne, with most disease transmission occurring in the summer months. Previous research has shown that Australian native possums are reservoirs of M. ulcerans and that they shed the bacteria in their fecal material (excreta). Field surveys show that locales where possums harbor M. ulcerans overlap with human cases of BU, raising the possibility of using possum excreta surveys to predict the risk of disease occurrence in humans., Methods: We thus established a highly structured 12 month possum excreta surveillance program across an area of 350 km 2 in the Mornington Peninsula area 70 km south of Melbourne, Australia. The primary objective of our study was to assess using statistical modeling if M. ulcerans surveillance of possum excreta provided useful information for predicting future human BU case locations., Results: Over two sampling campaigns in summer and winter, we collected 2,282 possum excreta specimens of which 11% were PCR positive for M. ulcerans -specific DNA. Using the spatial scanning statistical tool SaTScan , we observed non-random, co-correlated clustering of both M. ulcerans positive possum excreta and human BU cases. We next trained a statistical model with the Mornington Peninsula excreta survey data to predict the future likelihood of human BU cases occurring in the region. By observing where human BU cases subsequently occurred, we show that the excreta model performance was superior to a null model trained using the previous year's human BU case incidence data (AUC 0.66 vs 0.55). We then used data unseen by the excreta-informed model from a new survey of 661 possum excreta specimens in Geelong, a geographically separate BU endemic area to the southwest of Melbourne, to prospectively predict the location of human BU cases in that region. As for the Mornington Peninsula, the excreta-based BU prediction model outperformed the null model (AUC 0.75 vs 0.50) and pinpointed specific locations in Geelong where interventions could be deployed to interrupt disease spread., Conclusions: This study highlights the One Health nature of BU by confirming a quantitative relationship between possum excreta shedding of M. ulcerans and humans developing BU. The excreta survey-informed modeling we have described will be a powerful tool for the efficient targeting of public health responses to stop BU., Funding: This research was supported by the National Health and Medical Research Council of Australia and the Victorian Government Department of Health (GNT1152807 and GNT1196396)., Competing Interests: KV, AB, JP, AV, JW, KB, MD, VB, JF, ET, PJ, SW, NG, TS No competing interests declared, (© 2023, Vandelannoote, Buultjens et al.)

Background & Aims: Handgrip strength is commonly normalized or stratified by body size to define subgroup-specific cut-points and reference limits values. However, it remains unclear which anthropometric variable is most strongly associated with handgrip strength. We aimed to, in older adults with no self-reported mobility limitations, determine whether height, weight, and body mass index (BMI) were meaningfully associated with handgrip strength., Methods: This cross-sectional study included community-dwelling ambulant participants, and we identified 775 older adults who reported no difficulty walking 100 m, climbing stairs, and rising from the chair. Handgrip strength was measured with a digital dynamometer. Bayesian linear regression was used to estimate the probabilities that the positive associations of height, weight, and BMI with handgrip strength exceeded 0 kg (the null value) and 2.5 kg (the clinically meaningful threshold value)., Results: Mean handgrip strength was 22.1 kg (SD, 4) for women and 32.9 kg (SD, 6) for men. Body height, weight, and BMI had >99.9% probabilities of a positive association with handgrip strength; however, the associations of per interquartile increase in body weight and BMI with handgrip strength had low probabilities (<5%) of exceeding the clinically meaningful threshold of 2.5 kg. In contrast, body height had the highest probability (99.6%) of a clinically meaningful association with handgrip strength: adjusting for age and gender, handgrip strength was 3.2 kg (95% CrI, 2.7 to 3.8) greater in older adults 1.61 m tall than in older adults 1.51 m tall., Conclusions: In a large sample of mobile-intact older adults, handgrip strength differed meaningfully by body height. Although requiring validation, our findings suggest that future efforts should be directed at normalizing handgrip strength by body height to better define subgroup-specific handgrip weakness. A web-based application (https://sghpt.shinyapps.io/ippts/) was created to allow interactive exploration of predicted values and reference limits of age-, gender-, and height-subgroups., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: The conventional count-based physical frailty phenotype (PFP) dichotomizes its criterion predictors-an approach that creates information loss and depends on the availability of population-derived cut-points. This study proposes an alternative approach to computing the PFP by developing and validating a model that uses PFP components to predict the frailty index (FI) in community-dwelling older adults, without the need for predictor dichotomization., Methods: A sample of 998 community-dwelling older adults (mean [SD], 68 [7] years) participated in this prospective cohort study. Participants completed a multi-domain geriatric screen and a physical fitness assessment from which the count-based PFP and the 36-item FI were computed. One-year prospective falls and hospitalization rates were also measured. Bayesian beta regression analysis, allowing for nonlinear effects of the non-dichotomized PFP criterion predictors, was used to develop a model for FI ("model-based PFP"). Approximate leave-one-out (LOO) cross-validation was used to examine model overfitting., Results: The model-based PFP showed good calibration with the FI, and it had better out-of-sample predictive performance than the count-based PFP (LOO-R 2 , 0.35 vs 0.22). In clinical terms, the improvement in prediction (i) translated to improved classification agreement with the FI (Cohen's k w , 0.47 vs 0.36) and (ii) resulted primarily in a 23% (95%CI, 18-28%) net increase in FI-defined "prefrail/frail" participants correctly classified. The model-based PFP showed stronger prognostic performance for predicting falls and hospitalization than did the count-based PFP., Conclusion: The developed model-based PFP predicted FI and clinical outcomes more strongly than did the count-based PFP in community-dwelling older adults. By not requiring predictor cut-points, the model-based PFP potentially facilitates usage and feasibility. Future validation studies should aim to obtain clear evidence on the benefits of this approach., (© 2023. The Author(s).)

Background: Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes., Methods: Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6-1.0, P = 0.094)., Conclusion: Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Moyo 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.)

Background: Intrinsic capacity (IC) and frailty are complementary in advancing disability prevention through maintaining functionality., Objectives: We examined the relationship between IC and frailty status at baseline and 1-year, and evaluated if IC decline predicts frailty onset among robust older adults. The secondary objectives investigated associations between IC, physical fitness and health-related outcomes., Design: Prospective cohort study., Setting: Community-based assessments., Participants: Older adults aged>55 years, who were independent in ambulation (walking aids permitted)., Measurements: 5 domains of IC were assessed at baseline: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Composite IC (0-10) was calculated, with higher scores representing greater IC. Frailty status was based on modified Fried criteria, with frailty progression defined as incremental Fried score at 1-year., Results: 809 participants (67.6+6.8 years) had complete data for all 5 IC domains. 489 (60.4%) participants were robust but only 213 (26.3%) had no decline in any IC domain. Pre-frail and frail participants were more likely to exhibit decline in all 5 IC domains (p<0.05), with decremental composite IC [9 (8-9), 8 (6-9), 5.5 (4-7.5), p<0.001] across robust, prefrail and frail. IC was significantly associated with fitness performance, independent of age and gender. Higher composite IC reduced risk for frailty progression (OR=0.62, 95% CI 0.48-0.80), and reduced frailty onset among robust older adults (OR=0.53, 95% CI 0.37-0.77), independent of age, comorbidities and social vulnerability. Participants with higher IC were less likely to experience health deterioration (OR=0.70, 95% CI 0.58-0.83), falls (OR=0.76, 95% CI 0.65-0.90) and functional decline (OR=0.64, 95% CI 0.50-0.83) at 1-year., Conclusion: Declining IC may present before frailty becomes clinically manifest, increasing risk for poor outcomes. Monitoring of IC domains potentially facilitates personalized interventions to avoid progressive frailty., Competing Interests: All the authors have no conflict of interest or financial disclosure of note.

Background: The differential risk profiles associated with prefrailty may be attributable to underlying intrinsic capacity (IC)., Objectives: We examine (i) effect of a multi-domain physical exercise and nutrition intervention on pre-frailty reversal in community-dwelling older adults at 1-year, and (ii) whether IC contributes to pre-frailty reversal., Methods: Prefrail participants in this non-randomized study were invited to attend a 4-month exercise and nutritional intervention following a frailty screen in the community. Prefrailty was operationalized as (i) FRAIL score 1-2 or (ii) 0 positive response on FRAIL but with weak grip strength or slow gait speed based on the Asian Working Group for Sarcopenia cut-offs. Participants who fulfilled operational criteria for prefrailty but declined enrolment in the intervention programme served as the control group. All participants completed baseline IC assessment: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Reversal of prefrailty was defined as achieving a FRAIL score of 0, with unimpaired grip strength and gait speed at 1-year follow-up., Results: Of 81 participants (70.0 ± 6.6 years, 79.0% female), 52 participants (64.2%) were enrolled in the multi-domain intervention, and 29 participants (35.8%) who declined intervention constituted the control group. There was no difference in age, gender and baseline composite IC between groups. Reversal to robustness at 1-year was similar between intervention and control groups (30.8% vs. 44.8% respectively, p = 0.206). Reduced prevalence of depression was observed among participants in the intervention group at 1-year relative to baseline (7.8% vs. 23.1%, p = 0.022). In multiple logistic regression, intervention had no effect on prefrailty reversal, while higher composite IC exhibited reduced likelihood of remaining prefrail at 1-year (OR = 0.67, 95% CI 0.45-1.00, p = 0.049)., Conclusion: Focusing only on the locomotion and vitality domains through a combined exercise and nutritional intervention may not adequately address component domain losses to optimize prefrailty reversal. Future studies should examine whether an IC-guided approach to target identified domain declines may be more effective in preventing frailty progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tay, Tay, Mah, Latib and Ng.)

In recent years reported cases of Buruli ulcer, caused by Mycobacterium ulcerans, have increased substantially in Victoria, Australia, with the epidemic also expanding geographically. To develop an understanding of how M. ulcerans circulates in the environment and transmits to humans we analyzed environmental samples collected from 115 properties of recent Buruli ulcer cases and from 115 postcode-matched control properties, for the presence of M. ulcerans. Environmental factors associated with increased odds of M. ulcerans presence at a property included certain native plant species and native vegetation in general, more alkaline soil, lower altitude, the presence of common ringtail possums (Pseudocheirus peregrinus) and overhead powerlines. However, only overhead powerlines and the absence of the native plant Melaleuca lanceolata were associated with Buruli ulcer case properties. Samples positive for M. ulcerans were more likely to be found at case properties and were associated with detections of M. ulcerans in ringtail possum feces, supporting the hypothesis that M. ulcerans is zoonotic, with ringtail possums the strongest reservoir host candidate. However, the disparity in environmental risk factors associated with M. ulcerans positive properties versus case properties indicates the involvement of human behavior or the influence of other environmental factors in disease acquisition that requires further study., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Slow gait speed and sit-to-stand performance are associated with adverse clinical outcomes in older adults. Identifying older adults with functional performance "below norms" is the first step toward prevention. We aimed to (1) examine the associations of age, body height, and gender with gait speed and sit-to-stand performance and (2) develop subgroup-specific reference ranges in older adults with no self-reported mobility limitations., Design: Cross-sectional study., Setting and Participants: This study analyzed data from 775 community-dwelling older adults who reported no difficulty walking 100 m, climbing stairs, and rising from the chair., Methods: Gait speed and sit-to-stand performance were measured by the 10-m gait speed test and 5-times sit-to-stand test, respectively. Bayesian linear regression was used to derive 95% reference ranges for gait speed and sit-to-stand performance, defined by different levels of age, body height, and gender., Results: Overall, 95% reference range was 0.89-1.79 m/s for habitual gait speed and 7.4-27.9 stands/30 s for sit-to-stand pace. Age had the highest posterior probability (>99%) of a meaningful association with both functional outcomes. Additionally, height was strongly associated with gait speed: a 10-cm increase in height was associated with 0.07 m/s (95% credible interval, 0.05-0.10) faster gait speed. For sit-to-stand test, the lower 95% reference range limits tended to be similar across gender and gender-specific height subgroups, owing to the associations of faster sit-to-stand pace with shorter height and male gender. Because extensive tables of reference ranges are impractical, a web-based application (https://sghpt.shinyapps.io/ippts/) is created to provide subgroup-specific reference ranges., Conclusions and Implications: In a large sample of mobile-intact older adults, reference ranges for gait speed and sit-to-stand performance differed meaningfully by age. Furthermore, gait speed was stature dependent. Although requiring validation, our findings may be used to define subgroup-specific "below-range" values and to complement existing universal clinical cut points for gait speed and sit-to-stand performance., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Whole genome sequencing (WGS) is increasingly used by tuberculosis (TB) programs to monitor Mycobacterium tuberculosis ( Mtb ) transmission. We aimed to characterise the molecular epidemiology of TB and Mtb transmission in the low-incidence setting of Victoria, Australia, and assess the utility of WGS., Methods: WGS was performed on all first Mtb isolates from TB cases from 2017 to 2020. Potential clusters (≤12 single nucleotide polymorphisms [SNPs]) were investigated for epidemiological links. Transmission events in highly-related (≤5 SNPs) clusters were classified as likely or possible, based on the presence or absence of an epidemiological link, respectively. Case characteristics and transmission settings (as defined by case relationship) were summarised. Poisson regression was used to examine associations with secondary case number., Findings: Of 1844 TB cases, 1276 (69.2%) had sequenced isolates, with 182 (14.2%) in 54 highly-related clusters, 2-40 cases in size. Following investigation, 140 cases (11.0% of sequenced) were classified as resulting from likely/possible local-transmission, including 82 (6.4%) for which transmission was likely. Common identified transmission settings were social/religious (26.4%), household (22.9%) and family living in different households (7.1%), but many were uncertain (41.4%). While household transmission featured in many clusters ( n  = 24), clusters were generally smaller (median = 3 cases) than the fewer that included transmission in social/religious settings ( n  = 12, median = 7.5 cases). Sputum-smear-positivity was associated with higher secondary case numbers., Interpretation: WGS results suggest Mtb transmission commonly occurs outside the household in our low-incidence setting. Further work is required to optimise the use of WGS in public health management of TB., Funding: The Victorian Tuberculosis Program receives block funding for activities including case management and contact tracing from the Victorian Department of Health. No specific funding for this report was received by manuscript authors or the Victorian Tuberculosis Program, and the funders had no role in the study design, data collection, data analysis, interpretation or report writing., Competing Interests: None to declare., (© 2022 The Authors.)

Aim: In order to account for the variability in gait speed due to demographic factors, an observed gait speed value can be compared with its predicted value based on age, sex, and body height (observed gait speed divided by predicted gait speed, termed "GS%predicted" henceforth). This study aimed to examine the screening accuracy of an optimal GS%predicted threshold for prefrailty/frailty., Methods: This cross-sectional study included 998 community-dwelling ambulant participants aged >50 years (mean age = 68 years). Participants completed a multi-domain geriatric screen and a physical fitness assessment, from which the 10-m habitual gait speed, GS%predicted, Physical Frailty Phenotype (PFP) index, and 36-item Frailty Index (FI) were computed., Results: Based on the FI, ~49% of participants had pre-frailty or frailty. The optimal threshold of GS%predicted (0.93) had greater screening accuracy than the 1.0 m/s fixed threshold for gait speed (AUC, 0.65 vs. 0.60; DeLong's P < 0.001). Replacing gait speed with GS%predicted in the PFP improved its overall discrimination (AUC, 0.70 vs. 0.67 of original PFP; DeLong's P < 0.001)., Conclusions: Defining a "slow" gait speed by a GS%predicted value of <0.93 provided greater screening accuracy than the traditional 1.0 m/s threshold for gait speed. Our results also support the use of GS%predicted-derived PFP to identify older adults at risk of prefrailty/frailty. Geriatr Gerontol Int 2022; 22: 575-580., (© 2022 Japan Geriatrics Society.)

Background: Biodegradable polymer drug eluting stents (BP-DES) may offer the advantage of vascular healing in ST-segment elevation myocardial infarction (STEMI). Long-term outcome data comparing BP-DES and second-generation durable polymer drug eluting stents (DP-DES) in STEMI is lacking. This study aims to compare the long-term clinical outcomes of BP-DES versus second-generation DP-DES in STEMI., Methods: This is an observational study of consecutive patients with STEMI who received either BP-DES (n = 854) or DP-DES (n = 708) during primary percutaneous coronary intervention (PCI) from 1st February 2007 to 31st December 2016. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (MI), and target lesion revascularization with follow up till 30th November 2019., Results: The baseline demographics, lesion and procedural characteristic were similar between the two groups except for more prior MI and chronic obstructive pulmonary disease in the BP-DES group. At a median follow up of 4.2 years (interquartile range: 2.6-6.2 years), the incidence of TLF was similar between BP-DES and DP-DES (adjusted hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26). Likewise, incidence of major adverse cardiovascular events (MACE: all-cause death, any MI or target vessel revascularization) and definite stent thrombosis were similar in both groups (MACE: adjusted HR 1.04, 95% CI 0.82-1.32; definite stent thrombosis: adjusted HR 1.06, 95% CI 0.31-3.64)., Conclusion: Among patients with STEMI who underwent primary PCI, BP-DES and DP-DES implantation was associated with similar long-term clinical outcomes., Competing Interests: Declaration of competing interest Dr. Joshua P. Loh and Dr. Huay Cheem Tan received institutional research grant from Boston Scientific., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ 2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF., Competing Interests: The department of Cardiology at Leiden University receives unrestricted research grants from Abbott Vascular, Bayer, Biotronik, BIoventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis and Medtronic. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, MSD, Medtronic and Novartis. JJB received speaker fees from Abbott Vascular. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Le, Huang, Singh, Toh, Ewe, Tang, Loo, Bryant, Ang, Tay, Soo, Yip, Oon, Gong, Lunaria, Yong, Lee, Yeo, Chai, Goh, Ling, Ong, Richards, Delgado, Bax, Ding, Ling and Chin.)

Aims: Pulmonary artery pulsatility index (PAPi), defined as [(pulmonary artery systolic pressure - diastolic pulmonary artery pressure)/mean right atrial pressure], is a novel haemodynamic index that predicts right ventricular failure after myocardial infarction and left ventricular assist device implantation. We analysed if a low PAPi is associated with death in our 14 - ​year pulmonary arterial hypertension (PAH) registry., Methods: Consecutive patients with newly diagnosed PAH and complete haemodynamic data were prospectively enrolled into our standing registry between January 2003 and December 2016. PAPi was calculated from baseline invasive right heart catheterization data. A prognostic cut-off value was determined with a decision tree. Baseline characteristics of 'high' and 'low' PAPi groups based on this cut-off were compared, as well as odds of death and time-to-death., Results: One hundred and two patients were included. Mean age was 53 years, and 77% were women. Our multi-ethnic cohort was 64% Chinese, 23% Malay, and 10% Indian. The aetiologies were idiopathic (33%), connective tissue disease (31%), congenital heart disease (24%), and others (12%). The low PAPi group (<5.3) had a greater age (56 years vs. 49 years), lower pulmonary artery systolic pressure (71 mmHg vs. 85 mmHg), and higher mean right atrial pressure (14 mmHg vs. 6 mmHg). Mortality risk was higher in the low PAPi group (adjusted odds ratio: 2.98 and adjusted hazard ratio: 2.23). Mean right atrial pressure was the strongest predictor (hazard ratio 1.114, P = 0.009) when components of PAPi were analysed., Conclusions: Pulmonary artery pulsatility index was found to be predictive of mortality in PAH and may be a valuable marker for risk stratification. Its prognostic strength may be driven by mean right atrial pressure., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Left ventricular thrombus (LVT) is a common complication of acute myocardial infarction and is associated with morbidity from embolic complications. Predicting which patients will develop death or persistent LVT despite anticoagulation may help clinicians identify high-risk patients. We developed a random forest (RF) model that predicts death or persistent LVT and evaluated its performance. This was a single-center retrospective cohort study in an academic tertiary center. We included 244 patients with LVT in our study. Patients who did not receive anticoagulation (n = 8) or had unknown (n = 31) outcomes were excluded. The primary outcome was a composite outcome of death, recurrent LVT and persistent LVT. We selected a total of 31 predictors collected at the point of LVT diagnosis based on clinical relevance. We compared conventional regularized logistic regression with the RF algorithm. There were 156 patients who had resolution of LVT and 88 patients who experienced the composite outcome. The RF model achieved better performance and had an AUROC of 0.700 (95% CI 0.553-0.863) on a validation dataset. The most important predictors for the composite outcome were receiving a revascularization procedure, lower visual ejection fraction (EF), higher creatinine, global wall motion abnormality, higher prothrombin time, higher body mass index, higher activated partial thromboplastin time, older age, lower lymphocyte count and higher neutrophil count. The RF model accurately identified patients with post-AMI LVT who developed the composite outcome. Further studies are needed to validate its use in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: To evaluate care cascades for programmatic active case finding and latent TB infection (LTBI) management in young child TB contacts (aged <5 years) in Victoria, Australia., Design: This was a retrospective review of public health surveillance data to identify contacts of all pulmonary TB cases notified from 2016 to 2019., Results: Contact tracing identified 574 young child contacts of 251 pulmonary TB cases. Active TB was found in 28 (4.9%) contacts, none of whom had previously received bacille Calmette-Guérin vaccination, and 529 were tested for TB infection using the tuberculin skin test (TST). The overall TST positivity was 15.3% (95% CI 0.1-0.2). Among the 574 children, 150 (26.1%) were close contacts of sputum smear-positive cases and 25 (16.7%) of these were not referred to TB clinics. Of the 125 referred, 81 were considered to have LTBI, 79 agreed to commence TB preventive treatment (TPT) and 71 (89.9%) completed TPT. Following completion of TPT, no child was subsequently diagnosed with active TB., Conclusion: There was a high yield from active case finding and uptake of TPT. Notable losses in the cascade of care occurred around referral to tertiary clinics, but high treatment completion rates and good outcomes were found in those prescribed treatment., Competing Interests: Conflict of interests: none declared., (© 2021 The Union.)

Background: Left ventricular thrombus (LVT) formation is a significant complication of acute myocardial infarction (AMI) due to its embolic potential. However, managing LVT requires balancing therapeutic benefits against bleeding risks. Our study provides a risk-benefit analysis of various antithrombotic regimens on long-term outcomes in treating post-AMI LVT patients., Methods: We conducted a comprehensive literature search in Medline, Embase and SCOPUS up to 1 April 2020. All studies reporting outcomes of post-AMI LVT patients were included., Results: 17 studies were included in total. Anticoagulation (47-100%) and triple therapy use (38-100%) varied largely across studies. On meta-analysis, administration of anticoagulation (OR 0.14, 95% CI 0.05-0.36, p < 0.001) and triple therapy (OR 0.22, 95% CI 0.07-0.66, p < 0.001) resulted in lower odds of mortality. Neither anticoagulation (p = 0.24) nor triple therapy (p = 0.73) was associated with bleeding. Triple therapy was associated with LVT resolution on meta-analysis (OR 2.53, 95% CI 1.53-4.19, p < 0.001) and regression analysis (OR 1.28, 95% CI 1.03-1.58, p = 0.03). Anticoagulation and triple therapy were independent predictors of systemic embolism ([OR 0.67, 95% CI 0.49-0.93, p = 0.02] and [OR 0.82, 95% CI 0.73-0.93, p = 0.001]) and stroke ([OR 0.62, 95% CI 0.41-0.94, p = 0.03] and [OR 0.73, 95% CI 0.55-0.96, p = 0.03])., Conclusions: While there is clear therapeutic benefit in anticoagulation for post-AMI LVT, the extent of bleeding risk is uncertain. Future trials are necessary to determine the optimal antithrombotic strategy for post-AMI LVT management., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Preventing frailty is important to avoid adverse health outcomes. Intervention studies have largely focused on frail elderly, although the intermediate pre-frail state may be more amenable to improvement., Objectives: This study aims to assess how physical performance may change among pre-frail elderly enrolled in a pragmatic non-controlled exercise and nutritional intervention programme., Methods: This is a non-controlled study involving a 4-month exercise and nutritional intervention for community dwelling pre-frail older adults. Pre-frailty was defined as the presence of 1 or 2 positive responses on the FRAIL questionnaire, or evidence of weak grip strength (<26kg for males; <18kg for females) or slow gait speed (<0.8m/s) amongst participants who were asymptomatic on FRAIL. Physical performance in flexibility, grip and lower limb strength, endurance, balance, and Short Physical Performance Battery were measured at 3 time-points: baseline, 3-month from recruitment (without intervention), and immediate post-intervention. Repeated measures mixed model analysis was performed to compare physical performance measures across the 3 time-points., Results: 94 pre-frail participants were eligible for intervention, of whom 59 (mean age = 70.9±7.2 years) were ready for the post-intervention review. 21 (35.6%) transitioned to robust phenotype while 32 (54.2%) remained as pre-frail. Significant improvement post-intervention was observed in lower limb strength and power, evident on reduction in time taken for 5 sit-to-stand repetitions (0.46±0.20s, p=0.03). There was no significant change to the other physical performance measures examined., Conclusion: We observed reversibility of pre-frailty, and the benefit of multi-component intervention in improving physical performance of pre-frail older adults. The findings in this non-controlled study will need to be corroborated with future controlled trials., Competing Interests: The authors have no conflicts of interest to declare, financial or otherwise., (© 2021 - JARLIFE.)

Background: Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI)., Methods and results: This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000-1.011, P=0.029)., Conclusions: The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.

Background: The sit-to-stand (STS) test has been deployed as surrogate measures of strength or physical performance in sarcopenia diagnosis. This study examines the relationship of two common STS variants - Five Times Sit-to-Stand Test (5TSTS) and 30 s Chair Stand Test (30CST) - with grip strength, muscle mass and functional measures, and their impact on sarcopenia prevalence in community-dwelling older adults., Methods: This is a cross-sectional analysis of 887 community-dwelling adults aged ≥50 years. Participants completed a battery of physical fitness tests - 5TSTS, 30CST, grip strength, gait speed, Timed-Up-and-Go (TUG) for dynamic balance and six-minute walk test (6MWT) for cardiorespiratory endurance. Muscle mass was measured using multi-frequency segmental bioelectrical impedance analysis (BIA). We performed correlation analysis between STS performance and other fitness measures and muscle mass, followed by multiple linear regression for the independent determinants of STS performance., Results: Mean participant age was 67.3±7 years, with female predominance (72.9%). STS tests exhibited weak correlations with grip strength (30CST, r = 0.290; 5TSTS, r = - 0.242; both p< 0.01), and stronger correlations with gait speed (30CST, r = 0.517; 5TSTS, r = - 0.533; both p< 0.01), endurance (30CST, r = 0.558; 5TSTS, r = - 0.531; both p < 0.01) and dynamic balance (30CST, r = - 0.501; 5TSTS, r = 0.646; both p< 0.01). Muscle mass correlated with grip strength but not STS. In multiple regression analysis, all fitness measures were independently associated with 30CST performance. Performance in both STS tests remained independent of muscle mass. There was no significant difference in prevalence of possible sarcopenia diagnosis using grip strength or STS (30CST, 25.0%; 5TSTS, 22.1%; grip strength, 22.3%; p = 0.276). When both measures are used, prevalence is significantly higher (42.0%; p = 0.276). Prevalence of confirmed sarcopenia with inclusion of muscle mass was significantly lower using STS compared with grip strength (30CST, 4.6%; 5TSTS, 4.1% vs. grip strength, 7.1%; p< 0.05)., Conclusion: In the sarcopenia construct, STS tests better represents muscle physical performance rather than muscle strength. Different subsets of population with possible sarcopenia are identified depending on the test used. The lack of association of STS performance with muscle mass results in a lower prevalence of confirmed sarcopenia compared with grip strength, but may better reflect changes in muscle quality.

Background: Gender differences in valvular heart disease are increasingly recognised. A prior study has suggested better surgical outcomes in women with symptomatic aortic stenosis (AS). We investigate gender differences in medically managed severe AS., Method: We studied 347 patients with severe AS (aortic valve area index <0.6 cm 2 /m 2 ) in terms of baseline clinical background, echocardiographic characteristics, and clinical outcomes. Appropriate univariate and multivariate models were employed, while Kaplan-Meier curves were constructed to compare mortality outcomes., Results: In total, 205 (59%) patients were women. Despite higher incidences of hypertension (75.6% vs 47.3%) and diabetes mellitus (46.5% vs 29.5%) in women, women had improved survival (Kaplan-Meier log-rank = 6.24, p = 0.012). After adjusting for age (hazard ratio [HR], 1.034; 95% confidence interval [CI], 1.014-1.054), hypertension (HR, 1.469; 95% CI, 0.807-2.673), diabetes (HR, 1.219; 95% CI, 0.693-2.145), and indexed aortic valve area (HR 0.145, 95% CI 0.031-0.684) on multivariate analyses, female gender remained independently associated with lower mortality (HR, 0.561; 95%, CI 0.332-0.947). Women tended to have smaller body surface area (BSA), left ventricular (LV) internal diastolic diameter, and smaller LV outflow tract diameter but were similar to men in terms of LV ejection fraction, AS severity, and patterns of LV remodelling., Conclusions: Women appeared to have better outcomes compared to men in medically managed severe AS. These gender differences warrant further study and may affect prognosis, follow-up, and timing of valve surgery., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Abstract: Laboratory-confirmed infection with Mycobacterium ulcerans is currently notifiable to health departments in several jurisdictions. Accurate surveillance is imperative to understanding current and emerging areas of endemicity and to facilitate research into a neglected tropical disease with poorly-understood transmission dynamics. The state of Victoria currently reports some of the highest numbers of M. ulcerans cases in the world each year, with 340 cases notified in 2018 (an incidence of 5.5 per 100,000 population). In May 2019, a group of clinical, laboratory and public health experts met to discuss a new case definition for the surveillance of M. ulcerans disease in Victoria, incorporating clinical and epidemiological elements. The new case definition supports important public health messaging and actions for residents and visitors to popular tourist areas in Victoria., (© Commonwealth of Australia CC BY-NC-ND.)

Background: Left ventricular thrombosis (LVT) is a potentially devastating complication in post-acute myocardial infarction (AMI) patients. Previous studies have demonstrated that inflammation may contribute to thrombus formation, but its role on thrombus resolution is uncertain. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are easily accessible haematological markers of inflammation., Objectives: We aimed to identify differences between post-AMI LVT patients with and without LVT resolution, and to evaluate the utility of NLR and PLR in predicting LVT resolution., Methods: We included 289 consecutive post-AMI patients with LVT. Acute LVT was diagnosed based on echocardiogram. Patients were stratified based on LVT resolution. Logistic regression was performed to evaluate for independent predictors of thrombus resolution., Results: Compared to post-AMI patients with eventual LVT resolution, those with unresolved LVT had more co-morbidities such as hypertension (p = 0.003) and ischaemic heart disease (p < 0.001), fewer underwent percutaneous coronary intervention (PCI) (p < 0.001) or were treated with triple therapy (p < 0.001). NLR (p = 0.064) and PLR (p = 0.028) were higher in unresolved LVT patients. In non-PCI patients, NLR (OR 0.818, 95% CI 0.674-0.994, p = 0.043) and PLR (OR 0.989, 95% CI 0.979-0.999, p = 0.026) were independent predictors of thrombus resolution after adjustment for age and anticoagulation use., Conclusions: Post-AMI patients not receiving PCI may have a greater inflammatory response and a higher NLR and PLR, which is associated with less LVT resolution despite anticoagulation. Further studies are required to study this association., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The impact of the COVID-19 pandemic on the treatment of patient with aortic valve stenosis is unknown and there is uncertainty on the optimal strategies in managing these patients., Methods: This study is supported and endorsed by the Asia Pacific Society of Interventional Cardiology. Due to the inability to have face to face discussions during the pandemic, an online survey was performed by inviting key opinion leaders (cardiac surgeon/interventional cardiologist/echocardiologist) in the field of transcatheter aortic valve implantation (TAVI) in Asia to participate. The answers to a series of questions pertaining to the impact of COVID-19 on TAVI were collected and analyzed. These led subsequently to an expert consensus recommendation on the conduct of TAVI during the pandemic., Results: The COVID-19 pandemic had resulted in a 25% (10-80) reduction of case volume and 53% of operators required triaging to manage their patients with severe aortic stenosis. The two most important parameters used to triage were symptoms and valve area. Periprocedural changes included the introduction of teleconsultation, preprocedure COVID-19 testing, optimization of protests, and catheterization laboratory set up. In addition, length of stay was reduced from a mean of 4.4 to 4 days., Conclusion: The COVID-19 pandemic has impacted on the delivery of TAVI services to patients in Asia. This expert recommendation on best practices may be a useful guide to help TAVI teams during this period until a COVID-19 vaccine becomes widely available., (© 2020 Wiley Periodicals LLC.)

Background/purpose: Percutaneous coronary intervention (PCI) of diffuse coronary artery disease (CAD) is associated with higher adverse clinical events. This study aimed to compare the clinical outcomes of patients treated with single long 48 mm contemporary drug eluting stents (SL-DES) versus two overlapping contemporary drug eluting stents (OL-DES) for very-long CAD., Methods/materials: We analyzed the clinical outcome of 117 patients with SL-DES and 101 patients with OL-DES who underwent PCI between 1st July 2013 to 31st December 2016. The primary endpoint was target lesion failure (TLF) at two years, defined as a composite of cardiac mortality, target vessel myocardial infarction and target lesion revascularization., Results: Mean age was 60.8 ± 10.5 years for SL-DES group and 60.5 ± 11.9 years in the OL-DES group. SL-DES has longer mean lesion length as compared to OL-DES (43.1 ± 3.7 mm vs. 41.83 ± 2.3 mm p = 0.003). There was no difference in TLF at two years between SL-DES and OL-DES (5.3% vs. 6.4%, adjusted odds ratio 1.43, 95% CI 0.50-4.11). There was one case of probable ST in each group. Contrast volume usage was lower for SL-DES than OL-DES in patients who underwent single vessel PCI., Conclusions: Treatment of very-long CAD showed comparable TLF at two years for SL-DES versus OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Compare the diagnostic performance of FRAIL against Fried Phenotype and Frailty Index (FI), and identify clinical factors associated with pre-frailty/frailty., Design: Cross-sectional analysis., Setting: Community-based screenings in Senior Activity Centres, Residents' Corners and Community Centres in northeast Singapore., Participants: 517 community dwelling participants aged >55 years and ambulant independently (with/ without walking aids) were included in this study. Residents of sheltered or nursing homes, and seniors unable to ambulate at least four meters independently were excluded., Measurements: The multidomain geriatric screen included assessments for social vulnerability, mood, cognition, sarcopenia and nutrition. Participants completed a battery of physical fitness tests for grip strength, gait speed, lower limb strength and power, flexibility, balance and endurance, with overall physical performance represented by Short Physical Performance Battery (SPPB). Frailty status was assigned on FRAIL, Fried and 35-item FI., Results: Prevalence of frailty was 1.3% (FRAIL) to 3.1% (FI). Pre-frailty prevalence ranged from 17.0% (FRAIL) to 51.2% (FI). FRAIL demonstrated poor agreement with FI (kappa=0.171, p<0.0001), and Fried (kappa=0.194, p<0.0001). A lower FRAIL cut-off ≥1 yielded significantly improved AUC of 0.70 (95%CI 0.55 to 0.86, p=0.009) against Fried, and 0.71 (95%CI 0.55 to 0.86, p=0.008) against FI. All 3 frailty measures were diagnostic of impaired physical performance on SPPB, with AUCs ranging from 0.69 on FRAIL to 0.77 on Fried (all p values <0.01). Prevalence of low socio-economic status, depression, malnutrition and sarcopenia increased significantly, while fitness measures of gait speed, balance, and endurance declined progressively across robust, pre-frail and frail on all 3 frailty instruments (p <0.05)., Conclusions: Our results suggest that different frailty instruments may capture over-lapping albeit distinct constructs, and thus may not be used interchangeably. FRAIL has utility for quick screening, and any positive response should trigger further assessment, including evaluation for depression, social vulnerability and malnutrition., Competing Interests: All the authors have no conflict of interest or financial disclosure of note.

Background/purpose: Primary percutaneous coronary intervention (PCI) during acute ST-segment elevation myocardial infarction (STEMI) represents a thrombotic milieu and is associated with delayed healing after stenting. The pro-healing combination sirolimus eluting endothelial progenitor cell (EPC) capture stents encourage early endothelialization after stenting and may be beneficial in the STEMI population. We aim to evaluate the clinical outcomes one year and beyond for patients with STEMI who received the combination sirolimus eluting EPC capture stents during primary PCI., Methods/material: All STEMI patients implanted with combination sirolimus eluting EPC capture stents during primary PCI from November 2013 to December 2016 were enrolled. The primary outcome was target lesion failure (TLF) at in-hospital, one-month, one-year and beyond one year., Results: A total of 260 consecutive STEMI patients (283 lesions) were implanted with 313 combination sirolimus eluting EPC capture stents during primary PCI. Mean age was 56.1 ± 11.2 years and 88.8% were male. One in ten patients (10.9%) had cardiogenic shock on presentation, 7.3% needed mechanical ventilation and 7.7% had intra-aortic balloon pump inserted. A total of 97.9% of lesions achieve final TIMI 3 flow. Device success was seen in all patients. At extended follow up period (median 23.4 months), the clinical outcomes were TLF 8.8%, major adverse cardiovascular events 10.8%, cardiac mortality 4.2%, target vessel myocardial infarction 3.4%, target lesion revascularization 3.8%, and definite stent thrombosis 1.9%., Conclusions: This study demonstrated acceptable clinical outcomes for an all-comers STEMI patients undergoing primary PCI with the use of combination sirolimus eluting EPC cell capture stents., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Uncertainty regarding transmission pathways and control measures makes prompt presentation and diagnosis for Buruli ulcer critical. To examine presentation and diagnosis delays in Victoria, Australia, we conducted a retrospective study of 703 cases notified between 2011 and 2017, classified as residing in an endemic (Mornington Peninsula; Bellarine Peninsula; South-east Bayside and Frankston) or non-endemic area. Overall median presentation delay was 30 days (IQR 14-60 days), with no significant change over the study period ( p = 0.11). There were significant differences in median presentation delay between areas of residence ( p = 0.02), but no significant change over the study period within any area. Overall median diagnosis delay was 10 days (IQR 0-40 days), with no significant change over the study period ( p = 0.13). There were significant differences in median diagnosis delay between areas ( p < 0.001), but a significant decrease over time only on the Mornington Peninsula ( p < 0.001). On multivariable analysis, being aged <15 or >65 years; having non-ulcerative disease; and residing in the Bellarine Peninsula or South-East Bayside (compared to non-endemic areas) were significantly associated with shorter presentation delay. Residing in the Bellarine or Mornington Peninsula and being notified later in the study period were significantly associated with shorter diagnosis delay. To reduce presentation and diagnosis delays, awareness of Buruli ulcer must be raised with the public and medical professionals, particularly those based outside established endemic areas.

Acute ischemic stroke (AIS) is a feared complication in post-acute myocardial infarction (AMI) patients who develop left ventricular (LV) thrombus. There is limited data available on the incidence of stroke in this population, and characterisation of stroke subtypes has not been previously reported. Our study aims to evaluate the incidence of AIS in post-AMI patients with LV thrombus and to characterise the pattern of stroke subtypes. We screened 5829 patients with echocardiogram reports containing the "thrombus" keyword from August 2006 to September 2017. AIS that occurred after LV thrombosis was captured and relevant clinical data was collected. We identified 289 post-AMI patients with acute LV thrombus formation. Mean age was 59.3 ± 13.4 years. AIS occurred in 34 patients (11.8%), median duration of 20.5 days (IQR = 5.5-671.8) after LV thrombosis. Despite initial thrombus resolution, nine (5.2%) encountered AIS subsequently. Cardioembolic stroke subtype was identified in 76.5% of AIS, whilst 14.7% was small vessel disease and 8.8% was of large artery atherosclerosis subtype. Presence of thrombus protrusion (HR 3.04, 95% CI 1.25-7.41, p = 0.01), failure of initial thrombus resolution (HR 3.03, 95% CI 1.23-7.45, p = 0.02) and thrombus recurrence (HR 4.20, 95% CI 1.46-12.11, p < 0.01) were significant independent predictors for stroke. Incidence of AIS in this Asian population of post-AMI patients with LV thrombus was 11.8%. Duration of anticoagulation may need to be individualised for patients with higher risk for stroke occurrence after LV thrombosis.

Introduction: Frailty begins in middle life and manifests as a decline in functional fitness. We described a model for community frailty screening and factors associated with prefrailty and frailty and fitness measures to distinguish prefrail/frail from robust older adults. We also compared the Fatigue, Resistance, Ambulation, Illnesses and Loss of weight (FRAIL) scale against Fried frailty phenotype and Frailty Index (FI)., Materials and Methods: Community-dwelling adults ≥55 years old were designated robust, prefrail or frail using FRAIL. The multidomain geriatric screen included social profiling and cognitive, psychological and nutritional assessments. Physical fitness assessments included flexibility, grip strength, upper limb dexterity, lower body strength and power, tandem and dynamic balance and cardiorespiratory endurance., Results: In 135 subjects, 99 (73.3%) were robust, 34 (25.2%) were prefrail and 2 (1.5%) were frail. After adjusting for age and sex, depression (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.05-7.90; P = 0.040) and malnutrition (OR, 6.07; 95% CI, 2.52-14.64; P <0.001) were independently associated with prefrailty/frailty. Prefrail/frail participants had significantly poorer performance in upper limb dexterity ( P = 0.030), lower limb power ( P = 0.003), tandem and dynamic balance ( P = 0.031) and endurance ( P = 0.006). Except for balance and flexibility, all fitness measures differentiated prefrail/frail from robust women. In men, only lower body strength was significantly associated with frailty. Area under receiver operating characteristic curves for FRAIL against FI and Fried were 0.808 (0.688-0.927, P <0.001) and 0.645 (0.546-0.744, P = 0.005), respectively., Conclusion: Mood and nutrition are targets in frailty prevention. Physical fitness declines early in frailty and manifests differentially in both genders.

Right ventricle to pulmonary artery (RV-PA) conduits have been used for the surgical repair of congenital heart defects. These conduits frequently become stenosed or develop insufficiency with time, necessitating reoperations. Percutanous pulmonary valve implantation (PPVI) can delay the need for repeated surgeries in patients with congenital heart defects and degenerated RV-PA conduits. We presented our first experience with PPVI and described in detail the procedural methods and the considerations that are needed for this intervention to be successful. Immediate and short-term clinical outcomes of our patients were reported. Good haemodynamic results were obtained, both angiographically and on echocardiography. PPVI provides an excellent alternative to repeat open-heart surgery for patients with congenital heart defects and degenerated RV-PA conduits. This represents a paradigm shift in the management of congenital heart disease, which is traditionally managed by open-heart surgery., (Copyright: © Singapore Medical Association.)

Background: In current epidemiology of tuberculosis (TB), heterogeneity in infectiousness among TB patients is a challenge, which is not well studied. We aimed to quantify this heterogeneity and the presence of "super-spreading" events that can assist in designing optimal public health interventions., Methods: TB epidemiologic investigation data notified between 1 January 2005 and 31 December 2015 from Victoria, Australia were used to quantify TB patients' heterogeneity in infectiousness and super-spreading events. We fitted a negative binomial offspring distribution (NBD) for the number of secondary infections and secondary active TB disease each TB patient produced. The dispersion parameter, k, of the NBD measures the level of heterogeneity, where low values of k (e.g. k < 1) indicate over-dispersion. Super-spreading was defined as patients causing as many or more secondary infections as the 99th centile of an equivalent homogeneous distribution. Contact infection was determined based on a tuberculin skin test (TST) result of ≥10 mm. A NBD model was fitted to identify index characteristics that were associated with the number of contacts infected and risk ratios (RRs) were used to quantify the strength of this association., Results: There were 4190 (2312 pulmonary and 1878 extrapulmonary) index TB patients and 18,030 contacts. A total of 15,522 contacts were tested with TST, of whom 3213 had a result of ≥10 mm. The dispersion parameter, k for secondary infections was estimated at 0.16 (95%CI 0.14-0.17) and there were 414 (9.9%) super-spreading events. From the 3213 secondary infections, 2415 (75.2%) were due to super-spreading events. There were 226 contacts who developed active TB disease and a higher level of heterogeneity was found for this outcome than for secondary infection, with k estimated at 0.036 (95%CI 0.025-0.046). In regression analyses, we found that infectiousness was greater among index patients found by clinical presentation and those with bacteriological confirmation., Conclusion: TB transmission is highly over dispersed and super-spreading events are responsible for a substantial majority of secondary infections. Heterogeneity of transmission and super-spreading are critical issues to consider in the design of interventions and models of TB transmission dynamics.

Background and Objective: Pulmonary arterial hypertension (PAH) is a rare and fatal disease. Data from Asia are lacking compared with the West. We aim to describe disease characteristics in an ethnically diverse South-East Asian population and assess predictors for survival., Methods: We consecutively enrolled patients with PAH referred to our pulmonary hypertension specialty centre from January 2003 to December 2016. Baseline characteristics and survival were analysed. Based on a forward predictor selection procedure, a multi-level structural equation model was applied to identify predictors associated with mortality., Results: Out of 148 patients enrolled, 77% were females and mean age was 50.8 ± 15.9 years. Racial distribution was consistent with our population census. The most common aetiologies were congenital heart disease-associated PAH (35.8%), idiopathic PAH (29.7%) and then connective tissue disease-associated PAH (24.3%). Most patients presented in World Health Organization (WHO) Functional Class (FC) II (48.6%), followed by FC III (28.8%). Majority of patients (54.1%) were on phosphodiesterase type 5 (PDE5) inhibitor monotherapy. Survival rates were 85.8% at the end of the first year, 70.9% at 3 years, 66.9% at 5 years, 61.5% at 7 years and 55.4% at 10 years. The Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL) score (RS) was found to be the best predictor of mortality. A score > 6 was identified as a cut-off. Other predictors include mean right atrial pressure, heart rate, aetiology, age and N-terminal pro-brain natriuretic peptide., Conclusion: In this first registry study from a South-East Asian population, our survival rates are comparable with other national registries. The RS is validated in our population to be a good predictor of mortality., (© 2018 Asian Pacific Society of Respirology.)

Objectives: To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population., Background: Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months., Methods: This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015. The primary outcome was the incidence of TLF, defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization (TLR) at 1 year., Results: A total of 807 patients received the SYNERGY stent during the study period. One-year clinical outcome data was available for 765 patients (94.8%) and were considered for statistical analysis. The mean age was 60.7 ± 10.8 years, and 83.4% were males. Patients with acute myocardial infarction consisted of 50.3% (ST-segment elevation myocardial infarction: 23.0%, Non-ST-segment elevation myocardial infarction: 27.3%) of the study population. The treated lesions were complex (ACC/AHA type B2/C: 72.7%). The primary end point of TLF at 1 year was 5.8%. Rates of cardiac mortality, target vessel myocardial infarction, and TLR were 4.2, 1.0, and 1.3%, respectively, at 1 year. Predictors of the incidence and time to early TLF were female gender, Malay ethnicity, diabetes mellitus, acute myocardial infarction at presentation, a prior history of coronary artery bypass surgery and the presence of lesion calcification. The incidence of definite stent thrombosis was 0.4% at 1 year., Conclusions: In this registry, the use of the SYNERGY stent was associated with low rates of TLF at 1 year., (© 2018 Wiley Periodicals, Inc.)