Medicine (RMH) - Research Publications
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ItemNo Preview AvailableSustained benefits for thrombectomy triage using the act-fast algorithm after real-world implementation(SAGE, 2022-10-01)Background and Aims: The severity-based ACT-FAST algorithm for pre-hospital triage of large vessel occlusion (LVO) has previously been validated in a large paramedic-led study. We examined the subsequent real-world diagnostic utility of this tool for ambulance triage in the western metropolitan region of Melbourne, Australia. Methods: A manual audit was conducted of all patients presenting to a central comprehensive center for patients in the catchment of two spoke primary centers where ACT-FAST bypass was active from April 2020 to March 2021. Diagnostic performance was determined for LVO and overall need for comprehensive center care, including and excluding concurrent mobile stroke unit (MSU) cases. Results: Of 1222 presentations screened, 182 (15%) patients were in the bypass zone. These included 15 secondary inter-hospital LVO transfers, of which 9 had high severity (NIHSS⩾10). In contrast, 23 ACTFAST- Positive LVOs were bypassed (6 MSU-facilitated) in addition to 11 ICH and 1 intracerebral tumour. There were 8 bypassed false-positives (6 infarcts, 2 mimics) of which only 1 received thrombolysis. Bypassed patients received significantly faster EVT from ambulance dispatch (median 177min vs 237 min, p=0.001) whereas there was no significant difference in thrombolysis time (113min vs 101min, p=0.486). Conclusions: Implementation of ACT-FAST triaging avoided >70% of secondary transfers for high-severity LVO with significant time savings to thrombectomy and low rates of false-positive bypass (<1/month). Thrombolysis delay was minimal in our metropolitan setting and triage benefit was complementary to that provided by an active MSU service in the area.
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ItemNo Preview AvailableDUPILUMAB LEADS TO CLINICAL ASTHMA REMISSION INDICATIVE OF COMPREHENSIVE IMPROVEMENT IN PATIENTS WITH ASTHMA: RESULTS FROM THE LIBERTY ASTHMA QUEST AND TRAVERSE STUDIES(WILEY, 2022-10-01)Introduction: Asthma treatment response is ascertained by improvement in several important outcomes: exacerbations, symptom control, and lung function. A recent consensus framework defined criteria for remission in severe asthma. This post hoc analysis assessed clinical asthma remission following dupilumab treatment in the phase 3 QUEST (NCT02414854) and TRAVERSE (NCT02134028) studies using a multicomponent endpoint. Method: Patients with uncontrolled, non-OCS dependent, moderate-to-severe asthma received add-on dupilumab 200 mg or 300 mg every 2 weeks (q2w) or matched placebo for 52 weeks in QUEST, followed by add-on dupilumab 300 mg q2w for up to 96 weeks in TRAVERSE (dupilumab/dupilumab and placebo/dupilumab groups, respectively). Clinical asthma remission (no exacerbations and 5-item Asthma Control Questionnaire [ACQ-5] total score <1.5 and improvement in pre-bronchodilator forced expiratory volume in 1 second [FEV1] ≥ 100 mL [TRAVERSE] or either improvement in pre-bronchodilator FEV1 ≥ 100 mL, or post-bronchodilator percent predicted FEV1 ≥ 80% and no OCS use [QUEST]) was assessed at QUEST Week 52 and TRAVERSE Week 48 in patients with baseline eosinophils ≥150 cells/μL or FeNO ≥ 25 ppb. Results: 1519 patients from QUEST (dupilumab: n = 992; placebo: n = 527) and 1,227 QUEST patients who enrolled in TRAVERSE (dupilumab/dupilumab: n = 804; placebo/dupilumab: n = 423) were included in this post hoc analysis. At Week 52 of QUEST, 31.7% (314) dupilumab-treated vs. 17.7% (93) placebo-treated patients achieved all four criteria, meeting the requirements for clinical remission. At Week 48 of TRAVERSE, 36.4% (293) and 29.6% (125) of dupilumab/dupilumab and placebo/dupilumab patients met all criteria for clinical remission. Conclusion: Approximately 32% of patients in QUEST with elevated type 2 biomarkers and uncontrolled, moderate-to-severe asthma achieved a multicomponent endpoint representing clinical asthma remission after 1 year of dupilumab treatment. This percentage increased to 36% after an additional 48 weeks of treatment in TRAVERSE.
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ItemNo Preview AvailableLet's CHAT (Community Health Approaches to) Dementia in Aboriginal and Torres Strait Islander Community Controlled Primary Care: Baseline audit results of a stepped-wedge cluster randomised controlled trial(WILEY, 1/05/2021)Aim: This study describes baseline audit results documenting cognitive impairment not dementia (CIND) and dementia and associated risk factors in Aboriginal and Torres Strait Islander peoples aged ≥50 years attending Aboriginal Community Controlled Health Services (ACCHSs). Method: A specialised chart audit tool was designed to identify documented dementia and CIND, and relevant risk factor profiles in patient health records. The audits were conducted as part of a stepped-wedge cluster randomised controlled trial. Twelve Aboriginal Controlled Community Health Services (ACCHSs) in four states across Australia were recruited and medical records of 1,662 patients aged >50 years were audited. The primary outcome measure is documentation of CIND and dementia along with the associated risk factors. Results: The mean age was 60.2 +/-8.2 years and 56% were female. The overall prevalence of documented CIND or dementia was low, reported for only 57 (3.4%) patients audited. The prevalence of risk factors was high, with nearly two-thirds (64.1%,) having ≥4 risk factors. These included high rates of hypertension (52.5%), diabetes (44.3%), dyslipidemia (42.3%), obesity (35.3%) and current smoking (35.3%). Conclusion: Our previous work demonstrated the true prevalence of dementia was 10% and CIND was 10% in Indigenous communities. The low detection of these conditions in the primary care setting, accompanied by high prevalence of associated risk factors for cognitive impairment, demonstrates the need for dementia specific culturally responsive primary care interventions that optimise brain health and support identification of cognitive impairment and dementia, using a community wide and holistic approach across the lifespan.
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ItemDiagnosis, differential diagnosis and misdiagnosis of Susac syndrome(WILEY, 2022-06)BACKGROUND AND PURPOSE: Susac syndrome (SuS) is an inflammatory condition of the brain, eye and ear. Diagnosis can be challenging, and misdiagnosis is common. METHODS: This is a retrospective review of the medical records of 32 adult patients from an Australasian cohort of SuS patients. RESULTS: An alternative diagnosis prior to SuS was made in 30 patients (94%) with seven patients receiving two or more diagnoses. The median time to diagnosis of SuS was 3 months (range 0.5-100 months). The commonest misdiagnoses were migraine in 10 patients (31%), cerebral vasculitis in six (19%), multiple sclerosis in five (16%) and stroke in five (16%). Twenty-two patients were treated for alternative diagnoses, 10 of whom had further clinical manifestations prior to SuS diagnosis. At presentation seven patients (22%) met criteria for definite SuS, 19 (59%) for probable SuS and six (19%) for possible SuS. Six patients (19%) presented with brain-eye-ear involvement, 14 with brain-ear (44%), six with brain-eye (19%) and six (19%) with only brain involvement. In patients with the complete triad of symptoms the median delay to diagnosis was 3 months (range 1-9 months) compared to 5.25 months (range 0.5-100 months) for patients with encephalopathy and ocular symptoms at presentation. CONCLUSIONS: Susac syndrome patients are frequently misdiagnosed at initial presentation, despite many having symptoms or radiological features that are red flags for the diagnosis. Delayed diagnosis can lead to patient morbidity. The varied ways in which SuS can present, and clinician failure to consider or recognize SuS, appear to be the main factors leading to misdiagnosis.
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ItemNo Preview AvailableAssociations of DMT therapies with COVID-19 severity in multiple sclerosis(OXFORD UNIV PRESS, 2021-09)Abstract Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer-acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other) covariates were queried, alongside COVID-19 hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS phenotype, and EDSS. Results 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed/confirmed-only COVID-19, 20.9%/26.9% were hospitalised, 5.4%/7.2% were admitted to ICU, 4.1%/5.4% required artificial ventilation, and 3.2%/3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions Despite the cross-sectional design of this study, the internal and external consistency of these results with prior studies suggests their use may be a risk factor for more severe COVID-19. Key messages Anti-CD20 DMTs may be associated with worse COVID-19 severity amongst people with multiple sclerosis.
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ItemOutcomes of women at high familial risk for breast cancer: An 8-year single-center experience(WILEY, 2020-04)OBJECTIVES: The value of a high-risk surveillance program for mutation carriers and women at high familial breast cancer risk has not been extensively studied. A Breast and Ovarian Cancer Risk Management Clinic (BOCRMC) was established at the Royal Melbourne Hospital in 2010 to provide multimodality screening and risk management strategies for this group of women. The aims of this study were to evaluate the program and describe breast cancer diagnoses for BRCA1, BRCA2, and other germline mutation carriers as well as high-risk noncarriers attending the BOCRMC. METHODS: Clinical data from mutation carriers and noncarriers with a ≥25% lifetime risk of developing breast cancer who attended between 2010 and 2018 were extracted from clinic records and compared. The pattern and mode of detection of cancer were determined. RESULTS: A total of 206 mutation carriers and 305 noncarriers attended the BOCRMC and underwent screening on at least one occasion. Median age was 37 years. After a median follow-up of 34 months, 15 (seven invasive) breast cancers were identified in mutation carriers, with seven (six invasive) breast cancers identified in noncarriers. Of these, 20 (90.9%) were detected by annual screening, whereas two (9.1%) were detected as interval cancers (both in BRCA1 mutation carriers). Median size of the invasive breast cancers was 11 mm (range: 1.5-30 mm). The majority (76.9%) were axillary node negative. In women aged 25-49 years, the annualized cancer incidence was 1.6% in BRCA1, 1.4% in BRCA2 mutation carriers, and 0.5% in noncarriers. This compares to 0.06% annualized cancer incidence in the general Australian population. CONCLUSIONS: Screening was effective at detecting early-stage cancers. The incidence of events in young noncarriers was substantially higher than in the general population. This potentially justifies ongoing management through a specialty clinic, although further research to better personalize risk assessment in noncarriers is required.
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ItemNo Preview AvailableChallenges in data linkage - experiences from an upper gastrointestinal cancer data linkage study(OXFORD UNIV PRESS, 2021-09)Abstract Background Linked, population-level data is valuable for mapping patterns of care and evaluating health service utilisation, particularly in difficult-to-reach populations. Upper gastrointestinal (UGI) cancers have a dismal prognosis, creating difficulties engaging patients in research. The utility of a linked dataset in this population is of high value. Methods Key objectives included identifying the operational and feasibility issues associated with linking Australian state-based administrative and registry data for understanding health service utilisation in UGI cancers. Datasets pertained to hospital admissions, radiotherapy, community health, primary care, palliative care, Medicare and Pharmaceutical Benefits Schedule’s and UGI cancers. Results From a logistical perspective, data access request approval processes varied, with some requiring consent to be sought from individual services contributing data. The availability of unique person-level identifying information varied widely. Additionally, the time period of data capture differed between and within datasets, limiting the quality of the linked data. Significant costs were associated with linking with primary care and Medicare and Pharmaceutical Benefits Schedule’s. Federal dataset linkage required at least a one-year waiting period. Conclusions Whilst in theory data linkage is a powerful mechanism for obtaining population-level data, in reality, there are many logistical and financial barriers to linking multiple datasets. Consequently, critical data, which has the potential to inform policy and improve patient outcomes, cannot be procured. Key messages Logistical and financial challenges are associated with linking administrative and registry datasets for research, limiting the potential of data linkage.
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ItemNo Preview AvailableIntegrating Shared Survivorship Care into an Allogeneic Bone Marrow Transplant Long Term Follow up Service(ELSEVIER SCIENCE INC, 2020-03)
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