Publications by authors named "Leonid Churilov"

319 Publications

Cation leak underlies neuronal excitability in an HCN1 developmental and epileptic encephalopathy.

Brain 2021 Apr 1. Epub 2021 Apr 1.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.

Pathogenic variants in HCN1 are associated with developmental and epileptic encephalopathies. The recurrent de novo HCN1 M305L pathogenic variant is associated with severe developmental impairment and drug-resistant epilepsy. We engineered the homologue Hcn1 M294L heterozygous knock-in (Hcn1M294L) mouse to explore the disease mechanism underlying an HCN1 developmental and epileptic encephalopathy. The Hcn1M294L mouse recapitulated the phenotypic features of patients with the HCN1 M305L variant, including spontaneous seizures and a learning deficit. Active epileptiform spiking on the electrocorticogram and morphological markers typical of rodent seizure models were observed in the Hcn1M294L mouse. Lamotrigine exacerbated seizures and increased spiking, whereas sodium valproate reduced spiking, mirroring drug responses reported in a patient with this variant. Functional analysis in Xenopus laevis oocytes and layer V somatosensory cortical pyramidal neurons in ex vivo tissue revealed a loss of voltage dependence for the disease variant resulting in a constitutively open channel that allowed for cation 'leak' at depolarised membrane potentials. Consequently, Hcn1M294L layer V somatosensory cortical pyramidal neurons were significantly depolarised at rest. These neurons adapted through a depolarising shift in action potential threshold. Despite this compensation, layer V somatosensory cortical pyramidal neurons fired action potentials more readily from rest. A similar depolarised resting potential and left-shift in rheobase was observed for CA1 hippocampal pyramidal neurons. The Hcn1M294L mouse provides insight into the pathological mechanisms underlying hyperexcitability in HCN1 developmental and epileptic encephalopathy, as well as being a preclinical model with strong construct and face validity, on which potential treatments can be tested.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awab145DOI Listing
April 2021

Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial.

J Clin Neurosci 2021 Apr 2;86:103-109. Epub 2021 Feb 2.

Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia. Electronic address:

Aims: Pre-diabetes is a common condition that affects about 16.4% of Australian adults. Hyperglycaemia is a strong risk factor for the development of stroke. Metformin XR is an approved medication to treat type 2 diabetes in Australia but not pre-diabetes. Additionally, whether it is tolerated following a stroke is unclear. In this pilot study, we aimed to assess the feasibility of Metformin XR in people with stroke and pre-diabetes.

Methods: In this PROBE design trial, people who had recent stroke (within 3 months) with pre-diabetes were randomized to either the active arm (n = 13) receiving usual care plus Metformin XR (500 mg daily increased to a total daily dose of 1500 mg) or the control group receiving only usual care (n = 13). At baseline & after four months of intervention, clinical and biomedical characteristics, cardiovascular risk factors and medication data were recorded. At one month and 2.5 months into the study, compliance rateandside effects were determined.

Results: This trial showed that it is feasible to recruit, retain and monitor participants. However, the compliance rate was low. Adherence to metformin XR was 52% (IQR:42% to 61%) based on the remaining tablets in the container after 4 months of intervention. None of the reported side effects were deemed to be related to the study treatment and no significant differences were observed between the metformin XR and the control group.

Conclusion: Treatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe. Strategies are needed to improve adherence in future trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2021.01.006DOI Listing
April 2021

Safety of megadose of vitamin D in patients with nephrolithiasis.

Nutrition 2021 Feb 12;87-88:111201. Epub 2021 Feb 12.

Laboratory of the Mosaic of Autoimmunity, Saint Petersburg State University, Saint Petersburg, Russia.

Objective: This article describes two patients with renal lithiasis who received a megadose of 25-hydroxy vitamin D (25[OH]D) and had a good outcome.

Methods: The first case reports a 74-year-old man with a long-term history of renal lithiasis and about four episodes of renal crisis. He was treated once with extracorporeal shock wave lithotripsy. He also had a history of dyslipidemia, myocardial infarction, and stroke. Laboratory tests demonstrated 25(OH)D of 28 ng/mL (normal range (nr): >30 ng/mL), normal lipid levels, creatinine of 1.1 mg/dL, and homocysteine of 26.6 mcmol/L (nr: 5-15 mcmol/L); parathyroid hormone (PTH) was high at 67.3 pg/mL (nr: 10-65 pg/mL), serum total calcium was 8.6 mg/dL, 24-h urinary calcium was 139 mg/d (normal range 100-300 mg/d), and urinary sediment was normal. He received 50 000 IU per week of vitamin D for 3 mo, and 25(OH)D increased to 36.6 ng/mL. Urinary calcium was 142 mg/d, PTH was 46.7 pg/mL, and serum calcium was 9.6 mg/dL. No renal crisis was perceived. He asked for an alternative form of medication since he usually would forget to take drugs. Vitamin D in a single dose of 600 000 IU intramuscular was prescribed. He was asked to increase water intake to 2 to 3 L/d. After 3 mo his 25(OH)D was 75.0 ng/mL, serum calcium was 9.2 mg/dL, urinary calcium was 148 mg/d, and PTH was 38.7 pg/mL. He had no episodes of lithiasis renal crisis. Folic acid and methylcobalamin were added, and homocysteine normalized. At follow-up 3 y later, the patient was asymptomatic, cardiologic evaluation was stable without any other renal lithiasis crises, 25(OH)D continued to be normal at 62 ng/mL, and he received a megadose of vitamin D every 6 mo. Renal ultrasound revealed only microlithiasis. The second case reports a 52-year-old man with a long-term history of renal lithiasis experienced since he was 30 y old, with three renal crisis episodes. He was treated with an extracorporeal shock wave three times. Laboratory tests demonstrated 25(OH)D 18 ng/mL, normal biochemistry, total serum calcium of 10.2 mg/dL, 24-h urinary calcium of 154 mg/d, and normal urinary sediment. He received 50 000 IU per week of 25(OH)D for 3 mo, and 25(OH)D increased to 40.3 ng/mL. Urinary calcium was 167 mg/d, PTH was 35.3 pg/mL, and serum calcium was 10.1 mg/dL. No renal crisis was perceived. He asked for an alternative form of medication, and vitamin D in a single dose of 600 000 IU intramuscular was prescribed. He was asked to increase water intake to 2 to 3 L/d. After 3 mo, his 25(OH)D was 82.0 ng/mL, serum calcium was 9.6 mg/dL, urinary calcium was 175 mg/d, and PTH was 35.3 pg/mL. The renal ultrasound was unchanged. He had no episodes of lithiasis renal crisis. At follow-up 4 y later, the patient was asymptomatic without any other renal lithiasis crises, a renal ultrasound revealed a reduction of calculi size to microlithiasis, 25(OH)D continues normal, and he received a megadose of this vitamin every 4 mo.

Conclusion: To the best of our knowledge, this is the first description of a megadose of vitamin D used in patients with nephrolithiasis. Furthermore, this shows the safety of this strategy in patients without hypercalciuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nut.2021.111201DOI Listing
February 2021

Altering the rehabilitation environment to improve stroke survivor activity: A Phase II trial.

Int J Stroke 2021 Apr 13:17474930211006999. Epub 2021 Apr 13.

The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.

Background: Environmental enrichment involves organization of the environment and provision of equipment to facilitate engagement in physical, cognitive, and social activities. In animals with stroke, it promotes brain plasticity and recovery.

Aims: To assess the feasibility and safety of a patient-driven model of environmental enrichment incorporating access to communal and individual environmental enrichment.

Methods: A nonrandomized cluster trial with blinded measurement involving people with stroke ( = 193) in four rehabilitation units was carried out. Feasibility was operationalized as activity 10 days after admission to rehabilitation and availability of environmental enrichment. Safety was measured as falls and serious adverse events. Benefit was measured as clinical outcomes at three months, by an assessor blinded to group.

Results: The experimental group ( = 91) spent 7% (95% CI -14 to 0) less time inactive, 9% (95% CI 0-19) more time physically, and 6% (95% CI 2-10) more time socially active than the control group ( = 102). Communal environmental enrichment was available 100% of the time, but individual environmental enrichment was rarely within reach (24%) or sight (39%). There were no between-group differences in serious adverse events or falls at discharge or three months or in clinical outcomes at three months.

Conclusions: This patient-driven model of environmental enrichment was feasible and safe. However, the very modest increase in activity by people with stroke, and the lack of benefit in clinical outcomes three months after stroke do not provide justification for an efficacy trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/17474930211006999DOI Listing
April 2021

Factors associated with time to independent walking recovery post-stroke.

J Neurol Neurosurg Psychiatry 2021 Mar 17. Epub 2021 Mar 17.

Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Heidelberg, Victoria, Australia

Background: Past studies have inconsistently identified factors associated with independent walking post-stroke. We investigated the relationship between pre-stroke factors and factors collected acutely after stroke and number of days to walking 50 m unassisted using data from A Very Early Rehabilitation Trial (AVERT).

Methods: The outcome was recovery of 50 m independent walking, tested from 24 hours to 3 months post-stroke. A set of a priori defined factors (participant demographics: age, sex, handedness; pre-stroke: hypertension, ischaemic heart disease, hypercholesterolaemia, diabetes mellitus, atrial fibrillation; stroke-related: stroke severity, stroke type, ischaemic stroke location, stroke hemisphere, thrombolysis) were investigated for association with independent walking using a cause-specific competing risk Cox proportional hazards model. Respective effect sizes are reported as cause-specific adjusted HR (caHR) adjusted for age, stroke severity and AVERT intervention.

Results: A total of 2100 participants (median age 73 years, National Institutes of Health Stroke Scale 7, <1% missing data) with stroke were included. The median time to walking 50 m unassisted was 6 days (IQR 2-63) and 75% achieved independent walking by 3 months. Adjusted Cox regression indicated that slower return to independent walking was associated with older age (caHR 0.651, 95% CI 0.569 to 0.746), diabetes (caHR 0.836, 95% CI 0.740 to 0.945), severe stroke (caHR 0.094, 95% CI 0.072 to 0.122), haemorrhagic stroke (caHR 0.790, 95% CI 0.675 to 0.925) and right hemisphere stroke (caHR 0.796, 95% CI 0.714 to 0.887).

Conclusion: Our analysis provides robust evidence for important factors associated with independent walking recovery. These findings highlight the need for tailored mobilisation programmes that target subgroups, in particular people with haemorrhagic and severe stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2020-325125DOI Listing
March 2021

COVID-19 and ABO blood groups.

Isr Med Assoc J 2021 Mar;23(3):140-142

Laboratory of the Mosaic of Autoimmunity, Department of Pathology, Faculty of Medicine, Saint Petersburg State University, Russia.

View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease.

Antibodies (Basel) 2021 Feb 25;10(1). Epub 2021 Feb 25.

Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Yekaterinburg 620049, Russia.

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or "autoimmunodeficiency" could be the reason for disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antib10010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006153PMC
February 2021

Early Mobilization After Stroke: Do Clinical Practice Guidelines Support Clinicians' Decision-Making?

Front Neurol 2021 5;12:606525. Epub 2021 Feb 5.

National Health and Medical Research Council (NHMRC) Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery, Melbourne, VIC, Australia.

Early mobilization, out-of-bed activity, is a component of acute stroke unit care; however, stroke patient heterogeneity requires complex decision-making. Clinically credible and applicable CPGs are needed to support and optimize the delivery of care. In this study, we are specifically exploring the role of clinical practice guidelines to support individual patient-level decision-making by stroke clinicians about early mobilization post-stroke. Our study uses a novel, two-pronged approach. (1) A review of CPGs containing recommendations for early mobilization practices published after 2015 was appraised using purposely selected items from the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence (AGREE-REX) tool relevant to decision-making for clinicians. (2) A cross-sectional study involving semi-structured interviews with Australian expert stroke clinicians representing content experts and CPG target users. Every CPG was independently assessed against the AGREE-REX standard by two reviewers. Expert stroke clinicians, invited via email, were recruited between June 2019 to March 2020.The main outcomes from the review was the proportion of criteria addressed for each AGREE-REX item by individual and all CPG(s). The main cross-sectional outcomes were the distributions of stroke clinicians' responses about the utility of CPGs, specific areas of uncertainty in early mobilization decision-making, and suggested parameters for inclusion in future early mobilization CPGs. In 18 identified CPGs, many did not adequately address the "Evidence" and " AGREE-REX items. Out of 30 expert stroke clinicians (11 physicians [37%], 11 physiotherapists [37%], 8 nurses [26%]; median [IQR] years of experience, 14 [10-25]), 47% found current CPGs "too broad or vague," while 40% rely on individual clinical judgement and interpretation of the evidence to select an choice of action. The areas of uncertainty in decision-making revealed four key suggestions: (1) more granular descriptions of patient and stroke characteristics for appropriate tailoring of decisions, (2) clear statements about when clinical flexibility is appropriate, (3) detailed description of the intervention dose, and (4) physical assessment criteria including safety parameters. The lack of specificity, clinical applicability, and adaptability of current CPGs to effectively respond to the heterogeneous clinical stroke context has provided a clear direction for improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.606525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901923PMC
February 2021

Intrinsic hospital factors: overlooked cause for variations in delay to transfer for endovascular thrombectomy.

J Neurointerv Surg 2021 Feb 16. Epub 2021 Feb 16.

Department of Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Background: Intrinsic hospital factors leading to time delay to inter-hospital transfer for endovascular thrombectomy (EVT) have not been adequately investigated, leading to uncertainty in generalizability of hub and spoke EVT services. We investigated the contribution of intrinsic hospital factors to variations in time delay in a multicenter, retrospective study.

Methods: The setting was a hub and spoke EVT state-wide system for a population of 6.3 million and 34 spoke hospitals. We collected data on acute large vessel occlusion strokes transferred from spoke to hub for consideration of EVT between January 2016 and December 2018. The primary endpoint was the proportion of variability in delay-time in transfer cases contributed to by intrinsic hospital factors estimated through variance component analysis implemented as a mixed-effect linear regression model with hospitals as random effects.

Results: We included 434 patients. The median age was 72 years (IQR 62-79), 44% were female, and the median baseline National Institutes of Health Stroke Scale (NIHSS) was 16 (IQR 11-20). The median onset to CT time was 100 mins (IQR 69-157) at the spoke hospitals and CT acquisition at the spoke hospital to time of transfer was 93 min (IQR 70-132). 53% of the observed variability in time from CT acquisition at the spoke hospital to transfer to the EVT center was explained by intrinsic hospital factors, as opposed to patient-related factors.

Conclusions: Intrinsic hospital factors explained more than half of the observed variability in time from CT acquisition at the spoke hospital to departure for transfer. We recommend that the design of hub and spoke EVT services should account for intrinsic hospital factors to minimize hospital transfer delay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2020-016836DOI Listing
February 2021

Does Intravenous Thrombolysis Within 4.5 to 9 Hours Increase Clot Migration Leading to Endovascular Inaccessibility?

Stroke 2021 Mar 16;52(3):1083-1086. Epub 2021 Feb 16.

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital (A.B., H.M., B.C.V.C., M.W.P., S.M.D., G.A.D., B.Y.), University of Melbourne, Parkville, Australia.

Background And Purpose: Distal clot migration is a recognized event following intravenous thrombolysis (IVT) in the setting of acute ischemic stroke. Of note, clots that were initially retrievable by endovascular thrombectomy may migrate to a distal nonretrievable location and compromise clinical outcome. We investigated the incidence of clot migration leading to clot inaccessibility following IVT in the time window of 4.5 to 9 hours.

Methods: We performed a retrospective analysis of the EXTEND trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits) data. Baseline and 12- to 24-hour follow-up clot location was determined on computed tomography angiogram or magnetic resonance angiogram. The incidence of clot migration leading to a change from retrievable to nonretrievable location was identified and compared between the two treatment groups (IVT versus placebo).

Results: Two hundred twenty patients were assessed. Clot migration from a retrievable to nonretrievable location occurred in 37 patients: 21 patients (19.3%) in the placebo group and 16 patients (14.4%) in the IVT group. No significant difference was identified in the incidence of clot migration leading to inaccessibility between groups (=0.336).

Conclusions: Our results did not show increased clot migration leading to clot inaccessibility in patients treated with IVT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.030661DOI Listing
March 2021

Automated estimation of ischemic core prior to thrombectomy: comparison of two current algorithms.

Neuroradiology 2021 Feb 12. Epub 2021 Feb 12.

Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Grattan St, Parkville, Victoria, 3050, Australia.

Purpose: Endovascular thrombectomy (EVT) improves clinical outcomes in ischemic stroke with large vessel occlusion. Clinical benefits are inversely proportional to size of the pre-treatment ischemic core. This study compared estimated ischemic core volumes by two different CT perfusion (CTP) automated algorithms to the gold standard follow-up infarct volume using diffusion-weighted imaging (DWI) to assess for congruence, and thus eligibility for EVT.

Methods: Retrospective, single-center cohort study of 102 patients presenting to a comprehensive stroke center between 2012 and 2018. Inclusion criteria were CT perfusion prior to EVT, successful EVT with mTIBI 2b-3 reperfusion, and DWI post-EVT. CTP data were retrospectively processed by two algorithms: "delay and dispersion insensitive deconvolution" (DISD, RAPID software) versus "delay and dispersion corrected single value decomposition" (ddSVD, Mistar software), using commercially available software. Core volumes were compared to follow up DWI using independent software (MRIcron). Agreement between each algorithm and DWI was estimated using Lin's concordance coefficient and analyzed using reduced major axis regression.

Results: We included 102 patients. Both algorithms had excellent agreement with DWI (Lin's concordance coefficients: DISD 0.8 (95% CI: 0.73; 0.87), ddSVD 0.92 (95% CI: 0.89; 0.95). Compared to ddSVD (reduced major axis slope = 0.95), DISD exhibited a larger extent of proportional bias (slope = 1.12).

Conclusion: The ddSVD algorithm better correlates with DWI follow-up infarct volume than DISD processing. The DISD algorithm overestimated larger ischemic cores which may lead to patient exclusion from thrombectomy based on selection by core volume.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00234-021-02651-9DOI Listing
February 2021

Young Stroke Survivors' Preferred Methods of Meeting Their Unique Needs: Shaping Better Care.

Neurology 2021 03 10;96(13):e1701-e1710. Epub 2021 Feb 10.

From The Florey Institute of Neuroscience and Mental Health (J.K., K.B., H.J., J.B.), University of Melbourne, Heidelberg; St. Vincent's Hospital (K.B.), Melbourne; Austin Health Department of Medicine (L.C.), Heidelberg; Melbourne Brain Center (L.C.), Royal Melbourne Hospital; and Melbourne Medical School (L.C.), University of Melbourne, Australia.

Objective: To determine how young stroke survivors want their unmet needs to be addressed, we undertook an international online survey of people living with stroke.

Methods: Participants self-selected to complete an online survey that included a questionnaire on demographics and stroke-related characteristics, the Young Stroke Needs Screening Tool, and a questionnaire on how they wanted their needs to be met.

Results: One hundred seventy-one responses were received (68% female respondents, mean age 45 years, interquartile range 36-51 years). Preferences for methods of meeting needs varied depending on the domain of need and participants' demographic and stroke-related characteristics. Face-to-face contact with a health care professional was a popular means of meeting needs, but methods outside of a traditional health care setting such as a succinct list of tips or peer support were widely acceptable and sometimes preferred.

Conclusion: This work provides the impetus for developing alternative methods of meeting young stroke survivors' needs, many of which are not resource intensive or do not require an appointment with a health care professional.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000011647DOI Listing
March 2021

Factors associated with improved walking in older people during hospital rehabilitation: secondary analysis of a randomized controlled trial.

BMC Geriatr 2021 Jan 31;21(1):90. Epub 2021 Jan 31.

La Trobe Centre for Exercise and Sports Medicine Research, School of Allied Health, La Trobe University, Bundoora, Australia.

Background: Older people are often admitted for rehabilitation to improve walking, yet not everyone improves. The aim of this study was to determine key factors associated with a positive response to hospital-based rehabilitation in older people.

Methods: This was a secondary data analysis from a multisite randomized controlled trial. Older people (n= 198, median age 80.9 years, IQR 76.6- 87.2) who were admitted to geriatric rehabilitation wards with a goal to improve walking were recruited. Participants were randomized to receive additional daily physical therapy focused on mobility (n = 99), or additional social activities (n = 99). Self-selected gait speed was measured on admission and discharge. Four participants withdrew. People who changed gait speed ≥0.1 m/s were classified as 'responders' (n = 130); those that changed <0.1m/s were classified as 'non-responders' (n = 64). Multivariable logistic regression explored the association of six pre-selected participant factors (age, baseline ambulation status, frailty, co-morbidities, cognition, depression) and two therapy factors (daily supervised upright activity time, rehabilitation days) and response.

Results: Responding to rehabilitation was associated with the number of days in rehabilitation (OR 1.04; 95% CI 1.00 to 1.08; p = .039) and higher Mini Mental State Examination scores (OR 1.07, 95% CI 1.00 - 1.14; p = .048). No other factors were found to have association with responding to rehabilitation.

Conclusion: In older people with complex health problems or multi-morbidities, better cognition and a longer stay in rehabilitation were associated with a positive improvement in walking speed. Further research to explore who best responds to hospital-based rehabilitation and what interventions improve rehabilitation outcomes is warranted.

Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12613000884707; ClinicalTrials.gov Identifier NCT01910740 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12877-021-02016-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847572PMC
January 2021

Obstetric and perinatal outcomes for women with pre-existing diabetes in rural compared to metropolitan settings in Victoria, Australia.

Aust N Z J Obstet Gynaecol 2021 Jan 24. Epub 2021 Jan 24.

Mercy Perinatal, Mercy Hospital for Women, Melbourne, Victoria, Australia.

Background: Pre-existing diabetes in pregnancy is associated with an increased risk of complications. Likewise, living in rural, regional and remote Victoria, Australia, is also associated with poorer health outcomes. There is a gap in the literature with regard to whether Victorian women with pre-existing diabetes experience a greater risk of adverse pregnancy outcomes compared to their metropolitan counterparts.

Aim: Our objective is to compare obstetric and perinatal outcomes for women with pre-existing diabetes delivering in rural vs metropolitan hospitals in Victoria, Australia.

Materials And Methods: Retrospective population-based study using routinely collected state-based data of singleton births to women with type 1 and type 2 diabetes who delivered in metropolitan (n = 3233) and rural hospitals (n = 693) in Victoria, Australia, between 2006-2015. Pearson's χ test, Fisher's exact test and MannWhitney U-test were used to compare obstetric and perinatal outcomes between metropolitan and rural locations.

Results: Delivery in a rural hospital was associated with higher rates of stillbirth (2.3% vs 1.1%, P = 0.027), macrosomia (25.9% vs 16.9%, P < 0.001), shoulder dystocia (8.4% vs 3.5%, P < 0.001) and admission to the neonatal intensive care unit/special care nursery (73.2% vs 59.3%, P < 0.001). Smoking (18.0% vs 8.9%, P < 0.001), overweight/obesity (P = 0.047) and socioeconomic disadvantage (P < 0.001) were more common in rural women.

Conclusions: Women with pre-existing diabetes who deliver in rural hospitals experience a greater risk of adverse perinatal outcomes and present with increased maternal risk factors. These results suggest a need to improve care for women with pre-existing diabetes in rural Victoria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajo.13295DOI Listing
January 2021

Occlusive Disease and Upright Activity in Acute Ischemic Stroke.

J Stroke Cerebrovasc Dis 2021 Apr 18;30(4):105604. Epub 2021 Jan 18.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia; NHMRC Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery, Australia.

The impact of out-of-bed upright activity on outcomes in ischemic stroke patients with severe extra- and intracranial stenosis or occlusion is unknown. Using ultrasound findings from a cohort recruited to A Very Early Rehabilitation Trial (AVERT) which compared higher dose very early mobilisation (VEM) to usual care (UC), we aimed to explore the association between occlusive disease and 3-month outcomes and occlusive disease-by-mobilisation treatment interactions. Participants with ischemic stroke, with carotid and transcranial Doppler ultrasounds performed ≤1 week after admission, were included in this single centre substudy in Melbourne, Australia. Reports were retrospectively reviewed to determine the degree of stenosis or presence of occlusion in the relevant arterial territory. Stenosis ≥70% extracranial or ≥50% intracranial were classified as severe or occlusion. Overall, 19% (n = 36/191) had occlusive disease in the affected circulation. About 40% (n = 14/36) with occlusive disease and 51% (n = 79/155) without had a 3-month favourable outcome (mRS 0-2) (adjusted OR0.53, CI0.17-1.67). Fourteen percent (n = 5) with occlusive disease and 4% (n = 6) without died by 3 months (adjusted OR2.52, CI0.6-10.7). Fifty percent (n = 11/22) of UC (adjusted OR0.86, CI0.23-3.2) and 21% (n = 3/14) of VEM participants (adjusted OR0.16, CI0.01-2.7) with occlusive disease had a favourable outcome. Almost 30% (n = 4) VEM participants with occlusive disease died (adjusted OR3.99, CI0.69-22.9) compared to 5% (n = 1) UC participants with occlusive disease (adjusted OR0.45, CI0.02-8.6), however numbers were small. No stenosis-by-treatment interactions were found. High quality prospective studies are needed to help guide decision making about when patients with occlusive disease should commence upright activity in acute stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105604DOI Listing
April 2021

Dialysis and driving: An anonymous survey of patients receiving dialysis for end stage kidney disease.

Intern Med J 2021 Jan 19. Epub 2021 Jan 19.

Background: Driving is a complex task requiring multiple cognitive domains and the musculoskeletal system. Cognitive dysfunction is associated with driving impairment. Dialysis patients are known to have a high prevalence of cognitive impairment and other comorbidities, and may be at risk of driving impairment. No Australian guidelines address driving safety in dialysis patients.

Aims: To estimate the proportion of dialysis patients who were driving and those at risk of driving impairment, and to investigate the agreement between objective and subjective markers of risk.

Methods: This single centre study involved dialysis patients voluntarily completing two questionnaires relating to risk of driving impairment; the first questionnaire focused on objective markers, and the second questionnaire focused on subjective markers. Risk of driving impairment was established using pre-determined criteria, and the agreement between objective and subjective markers was estimated using Cohen's kappa.

Results: 44.8% (99/221) of patients participated; 76.8% (76/99) of participants were driving, and 76.3% (58/76) of drivers were at risk of driving impairment. Factors associated with at-risk driving included post dialysis dizziness, leg weakness or numbness, falling asleep whilst driving, and hypoglycaemia. Sixteen patients reported collisions since commencing dialysis. The questionnaires displayed slight agreement (Cohen's kappa = 0.20) between objective and subjective markers. This article is protected by copyright. All rights reserved.

Conclusions: Dialysis patients are at risk of driving impairment based on self-reported questionnaire responses. Discrepancies between patients' perceptions and objective markers were apparent. Further research into appropriate risk assessments, as well as development of guidelines to aid in determining driving safety in dialysis patients, is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imj.15198DOI Listing
January 2021

Advancing Stroke Recovery Through Improved Articulation of Nonpharmacological Intervention Dose.

Stroke 2021 Jan 12;52(2):761-769. Epub 2021 Jan 12.

Florey Institute of Neuroscience and Mental Health and NHMRC Centre of Research Excellence in Stroke Rehabilitation and Brain Recovery (J.B.), University of Melbourne, Heidelberg, Australia.

Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose reporting guidelines; (2) inadequate conceptualization of dose, which is multidimensional; and (3) unclear and inconsistent terminology that incorporates the multiple dose dimensions. To address these challenges, we need a well-conceptualized and consistent approach to dose articulation that can be applied across stroke recovery domains to stimulate critical thinking about dose during intervention development, as well as promote reporting of planned intervention dose versus actually delivered dose. We followed the Design Research Paradigm to develop a framework that guides how to articulate dose, conceptualizes the multidimensional nature and systemic linkages between dose dimensions, and provides reference terminology for the field. Our framework recognizes that dose is multidimensional and comprised of a duration of days that contain individual sessions and episodes that can be active (time on task) or inactive (time off task), and each individual episode can be made up of information about length, intensity, and difficulty. Clinical utility of this framework was demonstrated via hypothetical application to preclinical and clinical domains of stroke recovery. The suitability of the framework to address dose articulation challenges was confirmed with an international expert advisory group. This novel framework provides a pathway for better articulation of nonpharmacological dose that will enable transparent and accurate description, implementation, monitoring, and reporting, in stroke recovery research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.032496DOI Listing
January 2021

Early-phase dose articulation trials are underutilized for post-stroke motor recovery: A systematic scoping review.

Ann Phys Rehabil Med 2021 Jan 8:101487. Epub 2021 Jan 8.

Melbourne School of Health Sciences and Florey Institute of Neuroscience and Mental Health, University of Melbourne, 245 Burgundy Street, 3084, Heidelberg, Australia. Electronic address:

Background: To enable development of effective interventions, there is a need to complete systematic early-phase dose articulation research. This scoping review aimed to synthesize dose articulation research of behavioral motor interventions for stroke recovery.

Methods: MEDLINE and EMBASE were systematically searched for dose articulation studies. Preclinical experiments and adult clinical trials were classified based on the discovery pipeline and analyzed to determine which dose dimensions were articulated (time, scheduling or intensity) and how they were investigated (unidimensional vs multidimensional approach). Reporting of dose, safety and efficacy outcomes were summarized. The intervention description, risk of bias, and quality was appraised.

Results: We included 41 studies: 3 of preclinical dose preparation (93 rodents), 2 Phase I dose ranging (21 participants), 9 Phase IIA dose screening (198 participants), and 27 Phase IIB dose finding (1879 participants). All studies adopted a unidimensional approach. Time was the most frequent dimension investigated (53%), followed by intensity (29%), and scheduling (18%). Overall, 95% studies reported an efficacy outcome; however, only 65% reported dose and 45% reported safety. Across studies, 61% were at high risk of bias, and the average percentage reporting of intervention description and quality was 61% and 67%, respectively.

Conclusion: This review highlights a need to undertake more high-quality, early-phase studies that systematically articulate intervention doses from a multidimensional perspective in the field of behavioral motor stroke recovery. To address this gap, we need to invest in adapting early phase trial designs, especially Phase I, to support multidimensional dose articulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rehab.2021.101487DOI Listing
January 2021

Characteristics and in-hospital outcomes of patients requiring aeromedical retrieval for pregnancy, compared to non-retrieved metropolitan cohorts.

Aust N Z J Obstet Gynaecol 2021 Jan 10. Epub 2021 Jan 10.

Australian National University Medical School, College of Health and Medicine, The Australian National University, Canberra, Australian Capital Territory, Australia.

Background: Limited access to obstetrics and gynaecology (O&G) services in rural and remote Australia is believed to contribute to suboptimal birth outcomes.

Aims: To describe the characteristics of pregnancy aeromedical transfers, in-hospital outcomes, and patient access to O&G services, as compared to whole of Australia data.

Materials And Methods: We conducted a cohort study of women who required aeromedical retrieval for pregnancy-related issues between the 1 January 2015 and 31 December 2017.

Results: Hospital outcome data were collected on 2171 (65.2%) mothers and 2438 (100.0%) babies. The leading retrieval reason was threatened preterm labour and delivery (n = 883; 40.7%). Most patients were retrieved from rural and remote areas (n = 2224; 93.0%). Retrieved patients were significantly younger (28.0 vs 30.0 years, 95% CI 27.7-28.3), more likely to be overweight or obese (52.2% vs 45.1%, 95% CI 47.5-56.9) and to have smoked during their pregnancy (14.0% vs 9.9%, 95% CI 12.5-15.5) compared to Australian pregnant women overall. Over one-third of transferred women gave birth by Caesarean section (n = 812; 37.4%); the median gestational age at birth was 33.0 (95% CI 32.7-33.3) weeks. Early gestation is associated with low birth weights (median = 2579.5 g; 95% CI 2536.1-2622.9), neonatal resuscitation (35.4%, 95% CI 33.5-37.3), and special care nursery admission (41.2%, 95% CI 39.3-43.2). There were 42 (1.7%, 95% CI 1.2-2.2) stillbirths, which was significantly higher than seen Australia-wide (n = 6441; 0.7%).

Conclusion: This study found that pregnant women retrieved by the Royal Flying Doctor Service were younger, with higher rates of obesity and smoking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajo.13308DOI Listing
January 2021

Tenecteplase vs Alteplase Before Endovascular Therapy in Basilar Artery Occlusion.

Neurology 2021 03 6;96(9):e1272-e1277. Epub 2021 Jan 6.

From the Department of Medicine and Neurology (F. Alemseged, G.S., L.C., B.Y., M.W.P., S.M.D., P.J.M., N.Y. B.C.V.C.), University of Melbourne, and Department of Radiology (C.W., S.B., R.D.), Royal Melbourne Hospital, Parkville, Australia; Stroke Unit (F. Alemseged, A.R., F.S., M.D.) and Department of Biomedicine and Prevention (F.D.), University Hospital of Tor Vergata, Rome, Italy; Department of Neurology (F.C.N.), Austin Health, Melbourne, Australia; Department of Neurology (V.P.), Institute of Neuroradiology (D.K.), and Dresden Neurovascular Center (V.P., D.K.), University of Technology Dresden, Germany; Department of Interventional Neuroradiology (G.B.), Sainte-Anne-Hospital, Paris, France; Department of Neurology (T.J.K.), Royal Adelaide Hospital, Australia; Department of Neurology (T.Y.W.), Christchurch Hospital, New Zealand; Division of Medicine (D.S.), Princess Alexandra Hospital, Brisbane, Australia; NEUROFARBA Department (F. Arba), Careggi University Hospital, Florence; ASST Valcamonica (A.M.), Department of Neurology, Esine, Italy; Department of Neurosciences (H.M.D.), Eastern Health, Melbourne; Department of Neurology (P.B.), Gold Coast University Hospital, Queensland; Department of Neurology (B.O.), Gosford Hospital, New South Wales; and Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

Objective: To investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO).

Methods: To determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated.

Results: We included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years; median NIH Stroke Scale score 16 [interquartile range (IQR) 7-32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion >50% occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3-12; = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40-71] minutes) vs alteplase-treated patients (110 [IQR 51-185] minutes; = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase; = 0.9).

Conclusions: TNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted.

Clinicaltrialsgov Identifiers: NCT02388061 and NCT03340493.

Classification Of Evidence: This study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000011520DOI Listing
March 2021

In vivo microstructural heterogeneity of white matter lesions in healthy elderly and Alzheimer's disease participants using tissue compositional analysis of diffusion MRI data.

Neuroimage Clin 2020 26;28:102479. Epub 2020 Oct 26.

Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.

White matter hyperintensities (WMH) are regions of high signal intensity typically identified on fluid attenuated inversion recovery (FLAIR). Although commonly observed in elderly individuals, they are more prevalent in Alzheimer's disease (AD) patients. Given that WMH appear relatively homogeneous on FLAIR, they are commonly partitioned into location- or distance-based classes when investigating their relevance to disease. Since pathology indicates that such lesions are often heterogeneous, probing their microstructure in vivo may provide greater insight than relying on such arbitrary classification schemes. In this study, we investigated WMH in vivo using an advanced diffusion MRI method known as single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), which models white matter microstructure while accounting for grey matter and CSF compartments. Diffusion MRI data and FLAIR images were obtained from AD (n = 48) and healthy elderly control (n = 94) subjects. WMH were automatically segmented, and classified: (1) as either periventricular or deep; or (2) into three distance-based contours from the ventricles. The 3-tissue profile of WMH enabled their characterisation in terms of white matter-, grey matter-, and fluid-like characteristics of the diffusion signal. Our SS3T-CSD findings revealed substantial heterogeneity in the 3-tissue profile of WMH, both within lesions and across the various classes. Moreover, this heterogeneity information indicated that the use of different commonly used WMH classification schemes can result in different disease-based conclusions. We conclude that future studies of WMH in AD would benefit from inclusion of microstructural information when characterising lesions, which we demonstrate can be performed in vivo using SS3T-CSD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2020.102479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652769PMC
October 2020

Comparison of two questionnaires for assessment of emotional eating in people undergoing treatment for obesity.

Eat Weight Disord 2021 Jan 3. Epub 2021 Jan 3.

Department of Medicine (Austin Health), University of Melbourne, 145 Studley Road, Heidelberg, VIC, Australia.

Purpose: Emotional eating may contribute to weight gain and difficulty with weight loss. Questionnaires are currently the primary method used to identify this behaviour but there is no gold standard for detecting emotional eating, making it difficult to know which questionnaire to use for this purpose. This study assesses two questionnaires validated for assessment of emotional eating in patients with obesity, with the aim of investigating their interchangeability in the clinical setting.

Methods: 387 adult participants were recruited from the obesity treatment service at a tertiary metropolitan hospital. Responses were obtained for the 25-item Emotional Eating Scale (EES) and the 4-item coping subscale of the Palatable Eating Motives Scale (PEMS). Agreement was analysed using quadratically weighted Cohen's κ scores. Substantial agreement was defined as κ 0.61-0.80.

Results: The median (interquartile range) body mass index and age of participants was 42.1 kg/m (36.4-48.9 kg/m) and 51.6 years (41.1-61.4 years), respectively, and 70.5% of participants were female. The EES and PEMS were found to have substantial agreement (κ 0.71; 95% CI 0.65-0.76). Agreement remained substantial when analysing responses from men (0.61; 95% CI 0.47-0.73), women (0.73; 95% CI 0.67-0.79) and post-bariatric surgery patients (0.72; 95% CI 0.62-0.82) separately.

Conclusion: Despite focusing on different elements of emotional eating behaviour, the substantial agreement between the EES and PEMS coping subscale suggests that they identify respondents' susceptibility to emotional eating with consistency, including in people who have undergone bariatric surgery.

Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Clinical Trial Registration: This observational study has not been registered as a clinical trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40519-020-01084-2DOI Listing
January 2021

Role of Computed Tomography Perfusion in Identification of Acute Lacunar Stroke Syndromes.

Stroke 2021 01 2;52(1):339-343. Epub 2020 Dec 2.

Hunter Medical Research Institute and University of Newcastle, Australia (C.G.-E., F.M., T.L., C.R.L., N.J.S., M.W.P.).

Background And Purpose: Lacunar syndromes correlate with a lacunar stroke on imaging in 50% to 60% of cases. Computed tomography perfusion (CTP) is becoming the preferred imaging modality for acute stroke triage. We aimed to estimate the sensitivity, specificity, and predictive values for noncontrast computed tomography and CTP in lacunar syndromes, and for cortical, subcortical, and posterior fossa regions.

Methods: A retrospective analysis of confirmed ischemic stroke patients who underwent acute CTP and follow-up magnetic resonance imaging between 2010 and 2018 was performed. Brain noncontrast computed tomography and CTP were assessed independently by 2 stroke neurologists. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and area under the curve (AUC) for the detection of strokes in patients with lacunar syndromes using different CTP maps.

Results: We found 106 clinical lacunar syndromes, but on diffusion-weighted imaging, these consisted of 59 lacunar, 33 cortical, and 14 posterior fossa strokes. The discrimination of ischemia identification was very poor using noncontrast computed tomography in all 3 regions, but good for cortical (AUC, 0.82) and poor for subcortical and posterior regions (AUCs, 0.55 and 0.66) using automated core-penumbra maps. The addition of delay time and mean transient time maps substantially increased subcortical (AUC, 0.80) and slightly posterior stroke detection (AUC, 0.69).

Conclusions: Analysis of mean transient time and delay time maps in combination with core-penumbra maps improves detection of subcortical and posterior strokes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.030455DOI Listing
January 2021

Patterns of Infarction on MRI in Patients With Acute Ischemic Stroke and Cardio-Embolism: A Systematic Review and Meta-Analysis.

Front Neurol 2020 8;11:606521. Epub 2020 Dec 8.

Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, VIC, Australia.

Cardioembolic strokes are common however atrial fibrillation, the most common cause, is often asymptomatic and difficult to detect. There is evidence that infarct topography and volume on magnetic resonance imaging may be associated with specific stroke etiologies. A systematic review and meta-analysis were undertaken to summarize the available evidence on the association between stroke etiology, infarct topography, and volume. A systematic review was conducted using Medline (OVID), Embase (OVID), and PubMed databases. Hand searches of the gray literature and of reference lists in relevant articles were also performed. A quality assessment was undertaken, based on the STROBE checklist. For each study, the number of patients with and without a CE source of stroke and infarct topography was collected and outcomes presented as odds ratios (OR) with 95% CI and -values. Four thousand eight hundred and seventy-three patients with ischemic stroke were included, of whom 1,559 were determined to have a CE source. Bilateral infarcts (OR 3.41; 95% CI 2.20-5.29; < 0.0001) and multiple territory infarcts (OR 1.57; 95% CI 1.12-2.21; = 0.009) were more common in patients with a CE source of stroke, than patients without a CE source. Lacunar infarcts (OR 0.49; 95% CI 0.31-0.80; = 0.004) were more likely to occur in patients without a CE source. No significant difference between the frequency of multiple infarcts (OR 0.96; 95% CI 0.57-1.61; = 0.87) anterior circulation (OR 1.45; 95% CI 0.83-2.53; = 0.19) or posterior circulation infarcts (OR 1.06; 95% CI 0.72-1.57; = 0.75), between the two groups were identified. Three out of four studies examining volume, found a significant association between increased infarct volume and CE source of stroke. A sensitivity analysis with cryptogenic and undetermined stroke sources assumed to be cardioembolic, did not alter the associations observed. The findings of this systematic review and meta-analysis are broadly consistent with previous literature and provide more robust evidence on the association between infarct topography, volume and stroke etiology. Our findings may assist with refining cardiac investigations for patients with cryptogenic stroke, based on infarct topography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.606521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753023PMC
December 2020

Utility of Severity-Based Prehospital Triage for Endovascular Thrombectomy: ACT-FAST Validation Study.

Stroke 2021 01 22;52(1):70-79. Epub 2020 Dec 22.

Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital (H.Z., L.C., J.L.N., C.W., F.A., F.N., P.J.M., M.W.P., N.Y., S.M.D., B.C.V.C.), University of Melbourne, Australia.

Background And Purpose: Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm.

Methods: Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening.

Results: Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0-61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region.

Conclusions: The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.031467DOI Listing
January 2021

Influenza infection, SARS, MERS and COVID-19: Cytokine storm - The common denominator and the lessons to be learned.

Clin Immunol 2021 02 14;223:108652. Epub 2020 Dec 14.

Laboratory of the Mosaics of Autoimmunity, Saint Petersburg State University, Saint-Petersburg, Russian Federation; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Tel-Aviv University School of Medicine, Tel-Hashomer, Israel. Electronic address:

The outbreak of COVID-19 reminds us that the emerging and reemerging respiratory virus infections pose a continuing threat to human life. Cytokine storm syndromes of viral origin seem to have a common pathogenesis of the imbalanced immune response with the exaggerated inflammatory reaction combined with the reduction and functional exhaustion of T cells. Immunomodulatory therapy is gaining interest in COVID-19, but this strategy has received less attention in other respiratory viral infections than it deserved. In this review we suggest that based on the similarities of the immune dysfunction in the severe cases of different respiratory viral infections, some lessons from the immunomodulatory therapy of COVID-19 (particularly regarding the choice of an immunomodulatory drug, the selection of patients and optimal time window for this kind of therapy) could be applied for some cases of severe influenza infection and probably for some future outbreaks of novel severe respiratory viral infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clim.2020.108652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832378PMC
February 2021

A 2-Year Longitudinal Study of Physical Activity and Cardiovascular Risk in Survivors of Stroke.

Phys Ther 2021 Feb;101(2)

Physiotherapy Department, Alfred Health, Melbourne, Australia.

Objective: The purpose of this study was to explore associations between physical activity, cardiovascular risk factors, mobility, mood, fatigue, and cognition over 2 years following stroke rehabilitation discharge.

Methods: In this longitudinal observational study, survivors of first-ever stroke were evaluated at rehabilitation discharge and 6, 12, and 24 months later. Moderate to vigorous physical activity (MVPA) duration (minutes/day) assessed with an electronic monitor was the primary outcome. Further outcomes included step count, the number and duration of MVPA and sedentary bouts, cardiovascular risk factors (eg, blood pressure, fasting lipid profile, body mass index [BMI]), gait speed and endurance, mood, fatigue, and cognition. Associations between physical activity and cardiovascular risk factors over time were assessed with random-effects regression modeling. Associations between baseline characteristics and physical activity at 2 years were explored using regression modeling.

Results: Seventy-nine participants (68.4% men) with a mean age of 65 years (SD = 14) and a median gait speed of 1.2 m/s (interquartile range = 0.8 to 1.4) were included at baseline. Associations were found between higher physical activity (MVPA duration, number and duration of MVPA bouts) and lower BMI. Better gait speed, endurance, and cognition at baseline were associated with higher MVPA and step count at 2 years.

Conclusions: Duration and bouts of MVPA are associated with BMI. Increasing MVPA and bouts of MVPA may be a valuable treatment goal to reduce cardiovascular risk in survivors of stroke.

Impact: This 2-year study found that MVPA is associated with important cardiovascular risk factors in people who have survived stroke. Understanding these associations could be useful for developing effective treatments to prevent recurrent stroke.

Lay Summary: Performing MVPA and accumulating in bouts of at least 10 minutes might be challenging, but it could be an important component of treatments to reduce cardiovascular risk after stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ptj/pzaa205DOI Listing
February 2021

Prevalence and clinical associations of tau in Lewy body dementias: A systematic review and meta-analysis.

Parkinsonism Relat Disord 2020 11 23;80:184-193. Epub 2020 Sep 23.

Department of Medicine - The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.

Introduction: Alzheimer's disease neuropathologies (amyloid-β and tau) frequently co-exist to varying degrees in Lewy body dementias (LBD), which include dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).

Objectives: To investigate the prevalence of tau in DLB and PDD, and its associations with clinical outcomes.

Methods: We searched the major electronic databases using the search term: ("dementia with Lewy bodies" OR "diffuse Lewy body disease" OR "Lewy body variant of Alzheimer's disease") AND ("tau protein" OR "tauopathy" OR "neurofibrillary tangle"), for relevant studies which evaluated tau in LBD. Forty-nine articles met the inclusion criteria for data extraction. Where appropriate, a random-effect meta-analysis was performed to obtain pooled estimates for prevalence and risk ratios (RR) or standardized mean differences (SMD) for clinical features, diagnostic accuracy and cognition.

Results: Braak neurofibrillary tangle stage ≥ III was observed in 66% (n = 1511, 95%CI 60%-73%) of DLB and 52% (n = 433, 95%CI 27%-76%) of PDD at autopsy. Abnormal CSF phosphorylated-tau levels were present in 28% (n = 925, 95%CI 25%-31%) of DLB and 15% (n = 172, 95%CI 5%-24%) of PDD cases. Higher tau burden in DLB was associated with reduced likelihood of manifesting visual hallucinations (RR 0.56; 95%CI 0.40-0.77) and motor parkinsonism (RR 0.62; 95%CI 0.40-0.98), lower diagnostic accuracy of DLB during life (RR 0.49; 95%CI 0.38-0.64) and worse cognition prior to death (SMD 0.63; 95%CI 0.46-0.81).

Conclusions: Tau is common in LBD and may reduce clinical diagnostic accuracy in people with DLB. Prospective longitudinal studies are needed to understand the roles of co-morbid neuropathologies in Lewy body dementias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2020.09.030DOI Listing
November 2020