Medicine (Western Health) - Research Publications

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    The overlapping burden of the three leading causes of disability and death in sub-Saharan African children.
    Reiner, RC ; LBD Triple Burden Collaborators, ; Hay, SI (Springer Science and Business Media LLC, 2022-12-06)
    Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival.
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    Very early mobilization following acute stroke: Controversies, the unknowns, and a way forward
    Bernhardt, J (WOLTERS KLUWER MEDKNOW PUBLICATIONS, 2008-01)
    UNLABELLED: Evidence that organized stroke-unit care results in better outcome has led to positive changes in stroke service delivery around the world. It is well accepted that stroke rehabilitation should commence as early as possible for optimal recovery to be achieved. Exactly how early rehabilitation should start is controversial. Early mobilization (getting up out of bed within 24 h of stroke onset) is a wellestablished feature of acute stroke care in many Scandinavian hospitals. Elsewhere in the world, stroke protocols enforce bed rest for the first few days or foster long periods of bed rest after stroke. This paper aims to provide an overview of the topic of very early mobilization (VEM). It is divided into three sections: section 1 reviews the effects of bed rest and outlines arguments both for and against enforced bed rest after stroke; in section 2, VEM as a treatment for stroke and the limitations of existing literature in the field are described; and section 3 outlines the systematic approach that has been taken by our team of clinical researchers to the study the effect of VEM after stroke. CONCLUSION: VEM represents a simple, easy-to-deliver intervention, requiring little or no equipment. It is potentially deliverable to 85% of the acute stroke population and, if proven to be effective, may help reduce the significant personal and community burden of stroke. As current opinion about when mobilization should begin is divided, one way to move forward is through the conduct of a large high-quality clinical trial (such as A Very Early Rehabilitation Trial (AVERT)). Although some inroads have been made, further research in this field is clearly warranted.
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    Cadence Feedback and Video-Based Engagement Improves Motivation and Performance during Pedalling in Stroke Patients
    Soni, M ; Wijeratne, T ; Ackland, D (MDPI, 2022-07)
    Video and music as a dissociative attention stimulus during exercise is known to distract from the discomfort of physical exertion and improve exercise adherence; however, the influence of video-based feedback and engagement during pedalling on the performance and motivation of pedalling in stroke patients is poorly understood. The aim of this study was to employ a novel video-based engagement paradigm for pedalling in stroke patients and evaluate its capacity to influence the cadence control, physiological output, and perceived motivation and enjoyment. Thirteen stroke patients were recruited with low-to-moderate lower-limb disability (mean age: 64.0 yrs.). A reference group of 18 healthy young adult subjects (mean age: 27.7 yrs.) was also recruited to assess the broad applicability of the techniques to a contrasting non-pathological cohort. The participants pedalled at a slow (60 RPM) and fast (100 RPM) target speed with constant resistance in 15 min pedalling bouts that included (i) baseline pedalling with real-time visual feedback of cadence deviation from the target provided only in the first 20 s (ii) real-time visual feedback of cadence data over the entire pedalling session, and (iii) real-time engagement to maintain the playback rate of a prerecorded video by pedalling at the target speed. During low speed pedalling, stroke patients demonstrated significantly smaller absolute cadence deviation during pedalling with feedback (mean difference: 1.8 RPM, p = 0.014) and video-based engagement (mean difference: 2.4 RPM, p = 0.006) compared to the baseline pedalling. For the healthy adults, feedback and video-based engagement reduced cadence deviation significantly at all speeds (p < 0.05). All but one stroke patient either enjoyed or really enjoyed the video engagement during pedalling and felt motivated to undertake this form of exercise in therapy in the future. This proof-of-concept study showed that feedback and video-based engagement may improve the targeted pedalling performance in stroke patients, and by helping dissociate subjects from physical cues associated with fatigue, may ultimately improve exercise motivation and compliance.
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    Systematic Review of Existing Stroke Guidelines: Case for a Change
    Wijeratne, T ; Sales, C ; Wijeratne, C ; Karimi, L ; Jakovljevic, M ; Rahman Al-Tawaha, A (HINDAWI LTD, 2022-06-15)
    METHODS: We systematically searched for guideline recommendation on the day-to-day use of peripheral inflammatory markers such as NLR published in the English language between January 1, 2005, and October 2020. Any other evidence of system biology-based approach or recommendation was explored within the selected guidelines for this scoping review. Only the latest guideline per writing group was selected. Each guideline was analyzed independently by 2 to 4 authors to determine clinical scenarios explained/given, scientific evidence used, and recommendations presented in the context of system biology. RESULTS: The scoping review found 2,911 titles at the beginning of the search. Final review included with 15 guidelines. Stroke-related organizations wrote sixty-five percent of the guidelines while national ministries wrote a fewer number of guidelines. We were primarily interested in recommendations for acute management in AIS published in the English language. Fifteen eligible guidelines were identified from 15 different countries/regions. None of the guidelines recommended the routine use of peripheral markers of inflammation, such as NLR, among their acute assessment and management recommendations. None of the existing guidelines explored the system biology approach to one of the most complex diseases affecting the human brain, stroke. CONCLUSIONS: This systematic review has identified a significant evidence-practice gap in all existing national stroke guidelines published in English medium as of October 2020. These guidelines included the only current "living stroke guidelines," stroke guidelines from Australia with a real opportunity to modernize the living stroke guidelines with systems biology approach, and provide 2020 vision towards better stroke care globally. Investigation of complex disease such as stroke is best served through a systems biology approach. One of the easiest places to start is simple blood tests such as total white cell count and NLR. Systems biology approach point us towards simple tools such immune-inflammatory index (SII) and serial systemic immune inflammatory indices (SSIIi) which should pave the way for the stroke physician community address the challenges in systems biology approach in stroke care. These challenges include translating bench research to the bedside, managing big data (continuous pulse, blood pressure, sleep, oxygen saturation, progressive changes in NLR, SII, SSIIi, etc.). Working with an interdisciplinary team also provides a distinct advantage. Recent adoption of historic WHO-IGAP calls for immediate action. The 2022 World Brain Day campaign on Brain Health for All is the perfect opportunity to raise awareness and start the process.
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    Carotid artery stenosis and inflammatory biomarkers: the role of inflammation-induced immunological responses affecting the vascular systems
    Wijeratne, T ; Menon, R ; Sales, C ; Karimi, L ; Crewther, S (AME PUBLISHING COMPANY, 2020-10)
    The death, disability and economic cost of stroke are enormous. Indeed, among the 16 million people worldwide who suffer a stroke' annually, nearly six million die, and another five million are left permanently disabled making prevention of stroke one of the most important priorities in healthcare. Currently carotid artery stenosis (CS) or narrowing of the common carotid artery (CCA) or internal carotid artery (ICA) due to atherosclerotic plaque, accounts for 20-30% of all ischemic strokes. Atherosclerosis is now regarded as a chronic inflammatory disease in response to vascular compromise especially from hypertension. This has long been known to lead to inflammation and atherosclerotic plaque formation in the blood vessels. This mini-review aims to highlight the role of inflammation and neuro-immunological processes in carotid artery disease. Various cellular elements of inflammation and advanced imaging techniques have been identified as potential markers of plaque progression. Therapies related to decreasing and modulating immune-responsive inflammation in the carotid vessels have been shown to translate into decreased occurrence of acute neurologic events and improvement of clinical outcomes.
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    Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials
    Almekhlafi, MA ; Goyal, M ; Dippel, DWJ ; Majoie, CBLM ; Campbell, BCV ; Muir, KW ; Demchuk, AM ; Bracard, S ; Guillemin, F ; Jovin, TG ; Mitchell, P ; White, P ; Hill, MD ; Brown, S ; Saver, JL (AMER MEDICAL ASSOC, 2021-06)
    IMPORTANCE: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. OBJECTIVE: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). DATA SOURCES: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. STUDY SELECTION: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. DATA EXTRACTION/SYNTHESIS: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. MAIN OUTCOMES AND MEASURES: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. RESULTS: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. CONCLUSIONS AND RELEVANCE: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
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    Using electronic medical record data to assess chronic kidney disease, type 2 diabetes and cardiovascular disease testing, recognition and management as documented in Australian general practice: a cross-sectional analysis
    Jones, JL ; Lumsden, NG ; Simons, K ; Ta'eed, A ; de Courten, MP ; Wijeratne, T ; Cox, N ; Neil, CJA ; Manski-Nankervis, J-A ; Hamblin, PS ; Janus, ED ; Nelson, CL (BMJ PUBLISHING GROUP, 2022-02)
    OBJECTIVES: To evaluate the capacity of general practice (GP) electronic medical record (EMR) data to assess risk factor detection, disease diagnostic testing, diagnosis, monitoring and pharmacotherapy for the interrelated chronic vascular diseases-chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease. DESIGN: Cross-sectional analysis of data extracted on a single date for each practice between 12 April 2017 and 18 April 2017 incorporating data from any time on or before data extraction, using baseline data from the Chronic Disease early detection and Improved Management in PrimAry Care ProjecT. Deidentified data were extracted from GP EMRs using the Pen Computer Systems Clinical Audit Tool and descriptive statistics used to describe the study population. SETTING: Eight GPs in Victoria, Australia. PARTICIPANTS: Patients were ≥18 years and attended GP ≥3 times within 24 months. 37 946 patients were included. RESULTS: Risk factor and disease testing/monitoring/treatment were assessed as per Australian guidelines (or US guidelines if none available), with guidelines simplified due to limitations in data availability where required. Risk factor assessment in those requiring it: 30% of patients had body mass index and 46% blood pressure within guideline recommended timeframes. Diagnostic testing in at-risk population: 17% had diagnostic testing as per recommendations for CKD and 37% for T2D. Possible undiagnosed disease: Pathology tests indicating possible disease with no diagnosis already coded were present in 6.7% for CKD, 1.6% for T2D and 0.33% familial hypercholesterolaemia. Overall prevalence: Coded diagnoses were recorded in 3.8% for CKD, 6.6% for T2D, 4.2% for ischaemic heart disease, 1% for heart failure, 1.7% for ischaemic stroke, 0.46% for peripheral vascular disease, 0.06% for familial hypercholesterolaemia and 2% for atrial fibrillation. Pharmaceutical prescriptions: the proportion of patients prescribed guideline-recommended medications ranged from 44% (beta blockers for patients with ischaemic heart disease) to 78% (antiplatelets or anticoagulants for patients with ischaemic stroke). CONCLUSIONS: Using GP EMR data, this study identified recorded diagnoses of chronic vascular diseases generally similar to, or higher than, reported national prevalence. It suggested low levels of extractable documented risk factor assessments, diagnostic testing in those at risk and prescription of guideline-recommended pharmacotherapy for some conditions. These baseline data highlight the utility of GP EMR data for potential use in epidemiological studies and by individual practices to guide targeted quality improvement. It also highlighted some of the challenges of using GP EMR data.
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    Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study
    Mekkawy, DA ; Hamdy, S ; Abdel-Naseer, M ; Shehata, HS ; Halfawy, AA ; Shalaby, NM ; Shehata, GA ; Ali, AM ; Elmazny, A ; Ahmed, SM ; Ismail, JH ; Ibraheim, A ; Abdel-Hamid, HM ; Magdy, R ; Kabara Ayoub, Y ; Taha, AE ; Merghany, N ; Soliman, NM ; Elshebawy, H ; Abdelal, SES ; El-Ghoneimy, L ; Al-Athwari, A ; Kishk, NA ; Nada, MAF ; Farghaly, M ; Hassan, A ; Hegazy, MI ; Abdelalim, A ; Mourad, HS ; Hassouna, A ; Othman, AS ; Wijeratne, T (MDPI, 2022-01)
    BACKGROUND: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. METHODS: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. RESULTS: The patients' mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18-4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48-5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). CONCLUSIONS: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.
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    Vaccine Hesitancy during the Coronavirus Pandemic-Lessons from Polio
    Gunasekera, L ; Wijeratne, T (MDPI, 2021-11)
    The COVID-19 pandemic continues to cause disruptions to families, businesses and healthcare systems globally [...].
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    Disparities in Care and Outcome of Stroke Patients from Culturally and Linguistically Diverse Communities in Metropolitan Australia
    Rezania, F ; Neil, CJA ; Wijeratne, T (MDPI, 2021-12)
    Acute stroke is a time-critical emergency where diagnosis and acute management are highly dependent upon the accuracy of the patient's history. We hypothesised that the language barrier is associated with delayed onset time to thrombolysis and poor clinical outcomes. This study aims to evaluate the effect of language barriers on time to thrombolysis and clinical outcomes in acute ischemic stroke. Concerning the method, this is a retrospective study of all patients admitted to a metropolitan stroke unit (Melbourne, Victoria, Australia) with an acute ischemic stroke treated with tissue plasminogen activator between 1/2013 and 9/2017. Baseline characteristics, thrombolysis time intervals, length of stay, discharge destination, and in-hospital mortality were compared among patients with and without a language barrier using multivariate analysis after adjustment for age, sex, stroke severity, premorbid modified Rankin Scale (mRS), and Charlson Comorbidity Index (CCI). Language barriers were defined as a primary language other than English. A total of 374 patients were included. Our findings show that 76 patients (20.3%) had a language barrier. Mean age was five years older for patients with language barriers (76.7 vs. 71.8 years, p = 0.004). Less non-English speaking patients had premorbid mRS score of zero (p = 0.002), and more had premorbid mRS score of one or two (p = 0.04). There was no statistically significant difference between the two groups in terms of stroke severity on presentation (p = 0.06). The onset to needle time was significantly longer in patients with a language barrier (188 min vs. 173 min, p = 0.04). Onset to arrival and door to imaging times were reassuringly similar between the two groups. However, imaging to needle time was 9 min delayed in non-English speaking patients with a marginal p value (65 vs. 56 min, p = 0.06). Patients with language barriers stayed longer in the stroke unit (six vs. four days, p = 0.02) and had higher discharge rates than residential aged care facilities in those admitted from home (9.2% vs. 2.3%, p = 0.02). In-hospital mortality was not different between the two groups (p = 0.8). In conclusion, language barriers were associated with almost 14 min delay in thrombolysis. The delay was primarily attributable to imaging to needle time. Language barriers were also associated with poorer clinical outcomes.