Medicine (RMH) - Research Publications

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    Treating Us Right: A summary report describing and evaluating Wadja’s New Model of Care for Aboriginal Children and Families at The Royal Children’s Hospital
    Knoche, D ; CLARKE, A ; SHANAHAN, N ; ROWLEY, K (Onemda VicHealth Koori Health Unit, The University of Melbourne, 2012)
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    Screening, Diagnosis and Management of Sarcopenia and Frailty in Hospitalized Older Adults: Recommendations from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group
    Daly, RM ; Iuliano, S ; Fyfe, JJ ; Scott, D ; Kirk, B ; Thompson, MQ ; Dent, E ; Fetterplace, K ; Wright, ORL ; Lynch, GS ; Zanker, J ; Yu, S ; Kurrle, S ; Visvanathan, R ; Maier, AB (SPRINGER FRANCE, 2022-05-31)
    Sarcopenia and frailty are highly prevalent conditions in older hospitalized patients, which are associated with a myriad of adverse clinical outcomes. This paper, prepared by a multidisciplinary expert working group from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR), provides an up-to-date overview of current evidence and recommendations based on a narrative review of the literature for the screening, diagnosis, and management of sarcopenia and frailty in older patients within the hospital setting. It also includes suggestions on potential pathways to implement change to encourage widespread adoption of these evidence-informed recommendations within hospital settings. The expert working group concluded there was insufficient evidence to support any specific screening tool for sarcopenia and recommends an assessment of probable sarcopenia/sarcopenia using established criteria for all older (≥65 years) hospitalized patients or in younger patients with conditions (e.g., comorbidities) that may increase their risk of sarcopenia. Diagnosis of probable sarcopenia should be based on an assessment of low muscle strength (grip strength or five times sit-to-stand) with sarcopenia diagnosis including low muscle mass quantified from dual energy X-ray absorptiometry, bioelectrical impedance analysis or in the absence of diagnostic devices, calf circumference as a proxy measure. Severe sarcopenia is represented by the addition of impaired physical performance (slow gait speed). All patients with probable sarcopenia or sarcopenia should be investigated for causes (e.g., chronic/acute disease or malnutrition), and treated accordingly. For frailty, it is recommended that all hospitalized patients aged 70 years and older be screened using a validated tool [Clinical Frailty Scale (CFS), Hospital Frailty Risk Score, the FRAIL scale or the Frailty Index]. Patients screened as positive for frailty should undergo further clinical assessment using the Frailty Phenotype, Frailty Index or information collected from a Comprehensive Geriatric Assessment (CGA). All patients identified as frail should receive follow up by a health practitioner(s) for an individualized care plan. To treat older hospitalized patients with probable sarcopenia, sarcopenia, or frailty, it is recommended that a structured and supervised multi-component exercise program incorporating elements of resistance (muscle strengthening), challenging balance, and functional mobility training be prescribed as early as possible combined with nutritional support to optimize energy and protein intake and correct any deficiencies. There is insufficient evidence to recommend pharmacological agents for the treatment of sarcopenia or frailty. Finally, to facilitate integration of these recommendations into hospital settings organization-wide approaches are needed, with the Spread and Sustain framework recommended to facilitate organizational culture change, with the help of 'champions' to drive these changes. A multidisciplinary team approach incorporating awareness and education initiatives for healthcare professionals is recommended to ensure that screening, diagnosis and management approaches for sarcopenia and frailty are embedded and sustained within hospital settings. Finally, patients and caregivers' education should be integrated into the care pathway to facilitate adherence to prescribed management approaches for sarcopenia and frailty.
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    Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study
    Tan, N ; Ngu, N ; Worland, T ; Lee, T ; Abrahams, T ; Pandya, K ; Freeman, E ; Hannah, N ; Gazelakis, K ; Madden, RG ; Lynch, KD ; Valaydon, Z ; Sood, S ; Dev, A ; Bell, S ; Thompson, A ; Ding, J ; Nicoll, AJ ; Liu, K ; Gow, P ; Lubel, J ; Kemp, W ; Roberts, SK ; Majeed, A (SPRINGER, 2022-06-03)
    BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.
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    Weight is More Informative than Body Mass Index for Predicting Postmenopausal Breast Cancer Risk: Prospective Family Study Cohort (ProF-SC)
    Ye, Z ; Li, S ; Dite, GS ; Nguyen, TL ; MacInnis, RJ ; Andrulis, IL ; Buys, SS ; Daly, MB ; John, EM ; Kurian, AW ; Genkinger, JM ; Chung, WK ; Phillips, K-A ; Thorne, H ; Winship, IM ; Milne, RL ; Dugue, P-A ; Southey, MC ; Giles, GG ; Terry, MB ; Hopper, JL (AMER ASSOC CANCER RESEARCH, 2022-03-01)
    We considered whether weight is more informative than body mass index (BMI) = weight/height2 when predicting breast cancer risk for postmenopausal women, and if the weight association differs by underlying familial risk. We studied 6,761 women postmenopausal at baseline with a wide range of familial risk from 2,364 families in the Prospective Family Study Cohort. Participants were followed for on average 11.45 years and there were 416 incident breast cancers. We used Cox regression to estimate risk associations with log-transformed weight and BMI after adjusting for underlying familial risk. We compared model fits using the Akaike information criterion (AIC) and nested models using the likelihood ratio test. The AIC for the weight-only model was 6.22 units lower than for the BMI-only model, and the log risk gradient was 23% greater. Adding BMI or height to weight did not improve fit (ΔAIC = 0.90 and 0.83, respectively; both P = 0.3). Conversely, adding weight to BMI or height gave better fits (ΔAIC = 5.32 and 11.64; P = 0.007 and 0.0002, respectively). Adding height improved only the BMI model (ΔAIC = 5.47; P = 0.006). There was no evidence that the BMI or weight associations differed by underlying familial risk (P > 0.2). Weight is more informative than BMI for predicting breast cancer risk, consistent with nonadipose as well as adipose tissue being etiologically relevant. The independent but multiplicative associations of weight and familial risk suggest that, in terms of absolute breast cancer risk, the association with weight is more important the greater a woman's underlying familial risk. PREVENTION RELEVANCE: Our results suggest that the relationship between BMI and breast cancer could be due to a relationship between weight and breast cancer, downgraded by inappropriately adjusting for height; potential importance of anthropometric measures other than total body fat; breast cancer risk associations with BMI and weight are across a continuum.
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    Impact of a Mediterranean diet on hepatic and metabolic outcomes in non-alcoholic fatty liver disease: The MEDINA randomised controlled trial
    George, ES ; Reddy, A ; Nicoll, AJ ; Ryan, MC ; Itsiopoulos, C ; Abbott, G ; Johnson, NA ; Sood, S ; Roberts, SK ; Tierney, AC (WILEY, 2022-04-26)
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is predominantly managed by lifestyle intervention, in the absence of effective pharmacotherapies. Mediterranean diet (MedDiet) is the recommended diet, albeit with limited evidence. AIMS: To compare an ad libitum MedDiet to low-fat diet (LFD) in patients with NAFLD for reducing intrahepatic lipids (IHL) by proton magnetic resonance spectroscopy (1 H-MRS). Secondary outcomes include insulin resistance by homeostatic model of assessment (HOMA-IR), visceral fat by bioelectrical impedance analysis (BIA), liver stiffness measurement (LSM) and other metabolic outcomes. METHODS: In this parallel multicentre RCT, subjects were randomised (1:1) to MedDiet or LFD for 12 weeks. RESULTS: Forty-two participants (25 females [60%], mean age 52.3 ± 12.6 years) were included, 23 randomised to LFD and 19 to MedDiet.; 39 completed the study. Following 12 weeks, there were no between-group differences. IHL improved significantly within the LFD group (-17% [log scale]; p = .02) but not within the MedDiet group (-8%, p = .069). HOMA-IR reduced in the LFD group (6.5 ± 5.6 to 5.5 ± 5.5, p < .01) but not in the MedDiet group (4.4 ± 3.2 to 3.9 ± 2.3, p = .07). No differences were found for LSM (MedDiet 7.8 ± 4.0 to 7.6 ± 5.2, p = .429; LFD 11.8 ± 14.3 to 10.8 ± 10.2 p = .99). Visceral fat reduced significantly in both groups; LFD (-76% [log scale], p = <.0005), MedDiet (-61%, p = <.0005). CONCLUSIONS: There were no between-group differences for hepatic and metabolic outcomes when comparing MedDiet to LFD. LFD improved IHL and insulin resistance. Significant improvements in visceral fat were seen within both groups. This study highlights provision of dietary interventions in free-living adults with NAFLD is challenging.
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    Estimating the long-term effects of mass screening for latent and active tuberculosis in the Marshall Islands.
    Ragonnet, R ; Williams, BM ; Largen, A ; Nasa, J ; Jack, T ; Langinlur, MK ; Ko, E ; Rahevar, K ; Islam, T ; Denholm, JT ; Marais, BJ ; Marks, GB ; McBryde, ES ; Trauer, JM (Oxford University Press (OUP), 2022-10-13)
    BACKGROUND: Ambitious population-based screening programmes for latent and active tuberculosis (TB) were implemented in the Republic of the Marshall Islands in 2017 and 2018. METHODS: We used a transmission dynamic model of TB informed by local data to capture the Marshall Islands epidemic's historical dynamics. We then used the model to project the future epidemic trajectory following the active screening interventions, as well as considering a counterfactual scenario with no intervention. We also simulated future scenarios including periodic interventions similar to those previously implemented, to assess their ability to reach the End TB Strategy targets and TB pre-elimination in the Marshall Islands. RESULTS: The screening activities conducted in 2017 and 2018 were estimated to have reduced TB incidence and mortality by around one-third in 2020, and are predicted to achieve the End TB Strategy milestone of 50% incidence reduction by 2025 compared with 2015. Screening interventions had a considerably greater impact when latent TB screening and treatment were included, compared with active case finding alone. Such combined programmes implemented at the national level could achieve TB pre-elimination around 2040 if repeated every 2 years. CONCLUSIONS: Our model suggests that it would be possible to achieve TB pre-elimination by 2040 in the Marshall Islands through frequent repetition of the same interventions as those already implemented in the country. It also highlights the importance of including latent infection testing in active screening activities.
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    HALO CleanSpace PAPR evaluation: Communication, respiratory protection, and usability
    Ng, I ; Lee, K ; Kave, B ; Kluger, M ; Paynter, C ; Segal, R ; Krieser, RB ; Mezzavia, PM ; Hung, S ; Chen, Y ; Sindoni, T ; Williams, DL (CAMBRIDGE UNIV PRESS, 2022-04-01)
    OBJECTIVE: To evaluate a relatively new half-face-piece powered air-purifying respirator (PAPR) device called the HALO (CleanSpace). We assessed its communication performance, its degree of respiratory protection, and its usability and comfort level. DESIGN AND SETTING: This simulation study was conducted at the simulation center of the Royal Melbourne Hospital. PARTICIPANTS: In total, 8 voluntary healthcare workers participated in the study: 4 women and 4 men comprising 3 nursing staff and 5 medical staff. METHODS: We performed the modified rhyme test, outlined by the National Institute for Occupational Safety and Health (NIOSH), for the communication assessment. We conducted quantitative fit test and simulated workplace protection factor studies to assess the degree of respiratory protection for participants at rest, during, and immediately after performing chest compression. We also invited the participants to complete a usability and comfort survey. RESULTS: The HALO PAPR met the NIOSH minimum standard for speech intelligibility, which was significantly improved with the addition of wireless communication headsets. The HALO provided consistent and adequate level of respiratory protection at rest, during and after chest compression regardless of the device power mode. It was rated favorably for its usability and comfort. However, participants criticized doffing difficulty and perceived communication interference. CONCLUSIONS: The HALO device can be considered as an alternative to a filtering face-piece respirator. Thorough doffing training and mitigation planning to improve the device communication performance are recommended. Further research is required to examine its clinical outcomes and barriers that may potentially affect patient or healthcare worker safety.
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    Integrating the Biology of Cardiovascular Disease into the Epidemiology of Economic Decision Modelling via Mendelian Randomisation.
    Ademi, Z ; Morton, JI ; Liew, D ; Nicholls, SJ ; Zoungas, S ; Ference, BA (Springer Science and Business Media LLC, 2022-11)
    Health economic analyses are essential for health services research, providing decision-makers and payers with evidence about the value of interventions relative to their opportunity cost. However, many health economic approaches are still limited, especially regarding the primary prevention of cardiovascular disease (CVD). In this article, we discuss some limitations to current health economic models and then outline an approach to address these via the incorporation of genomics into the design of health economic models for CVD. We propose that when a randomised clinical trial is not possible or practical, health economic models for primary prevention of CVD can be based on Mendelian randomisation analyses, a technique to assess causality in observational data. We discuss the advantages of this approach, such as integrating well-known disease biology into health economic models and how this may overcome current statistical approaches to assessing the benefits of interventions. We argue that this approach may provide the economic argument for integrating genomics into clinical practice and the efficient targeting of newer therapeutics, transforming our approach to the primary prevention of CVD, thereby moving from reactive to preventive healthcare. We end by discussing some limitations and potential pitfalls of this approach.
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    Moving the field forward: detection of epileptiform abnormalities on scalp electroencephalography using deep learning-clinical application perspectives.
    Janmohamed, M ; Nhu, D ; Kuhlmann, L ; Gilligan, A ; Tan, CW ; Perucca, P ; O'Brien, TJ ; Kwan, P (Oxford University Press (OUP), 2022)
    The application of deep learning approaches for the detection of interictal epileptiform discharges is a nascent field, with most studies published in the past 5 years. Although many recent models have been published demonstrating promising results, deficiencies in descriptions of data sets, unstandardized methods, variation in performance evaluation and lack of demonstrable generalizability have made it difficult for these algorithms to be compared and progress to clinical validity. A few recent publications have provided a detailed breakdown of data sets and relevant performance metrics to exemplify the potential of deep learning in epileptiform discharge detection. This review provides an overview of the field and equips computer and data scientists with a synopsis of EEG data sets, background and epileptiform variation, model evaluation parameters and an awareness of the performance metrics of high impact and interest to the trained clinical and neuroscientist EEG end user. The gold standard and inter-rater disagreements in defining epileptiform abnormalities remain a challenge in the field, and a hierarchical proposal for epileptiform discharge labelling options is recommended. Standardized descriptions of data sets and reporting metrics are a priority. Source code-sharing and accessibility to public EEG data sets will increase the rigour, quality and progress in the field and allow validation and real-world clinical translation.
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    Incidence and risk factors of posttraumatic epilepsy following pediatric traumatic brain injury: A systematic review and meta-analysis
    Mariajoseph, FP ; Chen, Z ; Sekhar, P ; Rewell, SS ; O'Brien, TJ ; Antonic-Baker, A ; Semple, BD (WILEY, 2022-09-04)
    Posttraumatic epilepsy (PTE) is a well-known chronic complication following traumatic brain injury (TBI). Despite some evidence that age at the time of injury may influence the likelihood of PTE, the incidence of PTE in pediatric populations remains unclear. We therefore conducted a systematic review to determine the overall reported incidence of PTE, and explore potential risk factors associated with PTE after pediatric TBI. A comprehensive literature search of the PubMed, Embase, and Web of Science databases was conducted, including randomized controlled trials and cohort studies assessing the incidence of PTE in TBI pediatric patients. We excluded studies with a sample size of <10 patients and those in which a pediatric cohort was not clearly discernable. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We found that the overall incidence of PTE following pediatric TBI was 10% (95% confidence interval [CI] = 5.9%-15%). Subgroup analysis of a small number of studies demonstrated that the occurrence of early seizures (cumulative incidence ratio [CIR] = 7.28, 95% CI = 1.09-48.4, p = .040), severe TBI (CIR = 1.81, 95% CI = 1.23-2.67, p < .001), and intracranial hemorrhage (CIR = 1.60, 95% CI = 1.06-2.40, p = .024) increased the risk of PTE in this population. Other factors, including male sex and neurosurgical intervention, were nonsignificantly associated with a higher incidence of PTE. In conclusion, PTE is a significant chronic complication following childhood TBI, similar to in the adult population. Further standardized investigation into clinical risk factors and management guidelines is warranted. PROSPERO ID# CRD42021245802.