Publications by authors named "Anna He"

8 Publications

  • Page 1 of 1

Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study.

Lancet Neurol 2020 04 18;19(4):307-316. Epub 2020 Mar 18.

CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia. Electronic address:

Background: High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset.

Methods: In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0-2 years (early) or 4-6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0-10, with higher scores indicating increased disability), at 6-10 years after disease onset, assessed with a linear mixed-effects model.

Findings: We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7-8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 [SD 1·8] vs 3·5 [SD 2·1]; p<0·0001), with a difference between groups of -0·98 (95% CI -1·51 to -0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period.

Interpretation: High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6-10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy.

Funding: National Health and Medical Research Council Australia and MS Society UK.
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April 2020

Cognitive composite score association with Alzheimer's disease plaque and tangle pathology.

Alzheimers Res Ther 2018 09 11;10(1):90. Epub 2018 Sep 11.

Department of Neurobiology and Neurology, Barrow Neurological Institute, 350 W. Thomas Rd, Phoenix, AZ, 85013, USA.

Background: Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target either amyloid or tau, we sought to establish an association between a cognitive composite score and the underlying pathology of AD.

Methods: Data from 192 older deceased and autopsied persons from the Rush Religious Order Study were used in this study. All participants were classified at their initial evaluations with a clinical diagnosis of no cognitive impairment (NCI). Of these individuals, 105 remained NCI at the time of their death while the remaining 87 progressed to mild cognitive impairment (MCI) or AD. A cognitive composite score composed of eight cognitive tests was used as the outcome measure. Individuals were classified into groups based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological diagnosis and Braak stage.

Results: The rate of annualized composite score decline was significantly greater for the high CERAD (p < 0.001, d = 0.56) and Braak (p < 0.001, d = 0.55) groups compared with the low CERAD and Braak groups, respectively. Mixed-model repeated measure (MMRM) analyses revealed a significantly greater difference in composite score change from baseline for the high CERAD group relative to the low CERAD group after 5 years (Δ = -2.74, 95% confidence interval (CI) -5.01 to -0.47; p = 0.02). A similar analysis between low and high Braak stage groups found no significant difference in change from baseline (Δ = -0.69, 95% CI -3.03 to 1.66; p = 0.56).

Conclusions: These data provide evidence that decreased cognitive composite scores were significantly associated with increased AD pathology and provide support for the use of cognitive composite scores in AD prevention trials.
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September 2018

Every 15-min delay in recanalization by intra-arterial therapy in acute ischemic stroke increases risk of poor outcome.

Int J Stroke 2015 Oct 28;10(7):1062-7. Epub 2015 Apr 28.

Melbourne Brain Centre, Royal Melbourne Hospital, Melbourne, Vic., Australia.

Background: Intra-arterial therapy has improved recanalization rates compared with intravenous thrombolysis for acute ischemic stroke; however, superior clinical efficacy has not been convincingly demonstrated. Time to recanalization is postulated as a mechanism hindering the efficacy of intra-arterial therapy.

Aim: To investigate the effects of time to recanalization on clinical outcome postintra-arterial therapy for acute ischemic stroke.

Methods: Clinical data were collected prospectively for consecutive patients undergoing intra-arterial therapy for acute ischemic stroke at a single center between 2009 and 2013. Ninety-day functional outcome was assessed by the modified Rankin scale. Univariate analyses identified candidate clinical variables for inclusion in the multivariable model; multivariable logistic regression analyses identified variables independently associated with good outcome, defined as modified Rankin scale 0-2.

Results: One hundred and seven patients were included in the analysis. Median (interquartile range) age was 67 (54-77) years, 41 (38%) were female, and median (interquartile range) baseline National Institute of Health Stroke Severity score was 18 (13-22). Median time from symptom onset to recanalization was 330 min (interquartile range 277-397). Fifty-four (50%) patients achieved a favorable modified Rankin scale at 90 days. Age, successful recanalization, and time to recanalization were independently associated with good outcome at 90 days in multivariable logistic regression analysis. For every 15 min delay in recanalization, the odds of good outcome decreased by 10%.

Conclusions: Longer time to recanalization was associated with poorer functional outcome post intra-arterial therapy. We recommend that a systematic approach to minimize time delay to treatment is warranted in intra-arterial therapy for acute ischemic stroke.
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October 2015

Comparison of switch to fingolimod or interferon beta/glatiramer acetate in active multiple sclerosis.

JAMA Neurol 2015 Apr;72(4):405-13

Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia2Department of Medicine, University of Melbourne, Melbourne, Australia.

Importance: After multiple sclerosis (MS) relapse while a patient is receiving an injectable disease-modifying drug, many physicians advocate therapy switch, but the relative effectiveness of different switch decisions is often uncertain.

Objective: To compare the effect of the oral immunomodulator fingolimod with that of all injectable immunomodulators (interferons or glatiramer acetate) on relapse rate, disability, and treatment persistence in patients with active MS.

Design, Setting, And Participants: Matched retrospective analysis of data collected prospectively from MSBase, an international, observational cohort study. The MSBase cohort represents a population of patients with MS monitored at large MS centers. The analyzed data were collected between July 1996 and April 2014. Participants included patients with relapsing-remitting MS who were switching therapy to fingolimod or injectable immunomodulators up to 12 months after on-treatment clinical disease activity (relapse or progression of disability), matched on demographic and clinical variables. Median follow-up duration was 13.1 months (range, 3-80). Indication and attrition bias were controlled with propensity score matching and pairwise censoring, respectively. Head-to-head analyses of relapse and disability outcomes used paired, weighted, negative binomial models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity analyses were conducted.

Exposures: Patients had received fingolimod, interferon beta, or glatiramer acetate for a minimum of 3 months following a switch of immunomodulatory therapy.

Main Outcomes And Measures: Annualized relapse rate and proportion of relapse-free patients, as well as the proportion of patients without sustained disability progression.

Results: Overall, 379 patients in the injectable group were matched to 148 patients in the fingolimod group. The fingolimod group had a lower mean annualized relapse rate (0.31 vs 0.42; 95% CI, 0.02-0.19; P=.009), lower hazard of first on-treatment relapse (hazard ratio [HR], 0.74; 95% CI, 0.56-0.98; P=.04), lower hazard of disability progression (HR, 0.53; 95% CI, 0.31-0.91; P=.02), higher rate of disability regression (HR, 2.0; 95% CI, 1.2-3.3; P=.005), and lower hazard of treatment discontinuation (HR, 0.55; P=.04) compared with the injectable group.

Conclusions And Relevance: Switching from injectable immunomodulators to fingolimod is associated with fewer relapses, more favorable disability outcomes, and greater treatment persistence compared with switching to another injectable preparation following on-treatment activity of MS.
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April 2015

Transcriptome analysis of Houttuynia cordata Thunb. by Illumina paired-end RNA sequencing and SSR marker discovery.

PLoS One 2014 2;9(1):e84105. Epub 2014 Jan 2.

The College of Life Science, Huaihua University, Huaihua, China ; Key Laboratory of Hunan Province for Study and Utilization of Ethnic Medicinal Plant Resources, Huaihua, China ; Key Laboratory of Hunan Higher Education for Hunan-Western Medicinal Plant and Ethnobotany, Huaihua, China.

Background: Houttuynia cordata Thunb. is an important traditional medical herb in China and other Asian countries, with high medicinal and economic value. However, a lack of available genomic information has become a limitation for research on this species. Thus, we carried out high-throughput transcriptomic sequencing of H. cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development.

Principal Findings: Illumina paired-end sequencing technology produced over 56 million sequencing reads from H. cordata mRNA. Subsequent de novo assembly yielded 63,954 unigenes, 39,982 (62.52%) and 26,122 (40.84%) of which had significant similarity to proteins in the NCBI nonredundant protein and Swiss-Prot databases (E-value <10(-5)), respectively. Of these annotated unigenes, 30,131 and 15,363 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. In addition, 24,434 (38.21%) unigenes were mapped onto 128 pathways using the KEGG pathway database and 17,964 (44.93%) unigenes showed homology to Vitis vinifera (Vitaceae) genes in BLASTx analysis. Furthermore, 4,800 cDNA SSRs were identified as potential molecular markers. Fifty primer pairs were randomly selected to detect polymorphism among 30 samples of H. cordata; 43 (86%) produced fragments of expected size, suggesting that the unigenes were suitable for specific primer design and of high quality, and the SSR marker could be widely used in marker-assisted selection and molecular breeding of H. cordata in the future.

Conclusions: This is the first application of Illumina paired-end sequencing technology to investigate the whole transcriptome of H. cordata and to assemble RNA-seq reads without a reference genome. These data should help researchers investigating the evolution and biological processes of this species. The SSR markers developed can be used for construction of high-resolution genetic linkage maps and for gene-based association analyses in H. cordata. This work will enable future functional genomic research and research into the distinctive active constituents of this genus.
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November 2014

Hyperdense middle cerebral artery sign is associated with increased risk of hemorrhagic transformation after intravenous thrombolysis for patients with acute ischaemic stroke.

J Clin Neurosci 2013 Jul 9;20(7):984-7. Epub 2013 May 9.

Department of Neurology, Tianjin Medical University General Hospital, Heping District, Tianjin, China.

Haemorrhagic transformation (HT) is an infrequent but serious complication of intravenous thrombolysis therapy (IVT) for acute ischemic stroke. The hyperdense middle cerebral artery sign (HMCAS) is a possible radiological predictor. We aimed to assess the association between HMCAS and HT in a retrospective study. We included all patients with acute anterior circulation ischaemic stroke who received IVT between October 2007 and December 2011. Baseline characteristics were collected, including demographics, stroke risk factors and stroke type. Presence of HMCAS on baseline CT scans was evaluated. Follow-up CT scans were examined for HT, categorised according to the European Australasian Acute Stroke Study (ECASS) classification. The presence of symptomatic intracerebral haemorrhage (sICH) was defined according to Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST) criteria. The association between HT and HMCAS was assessed by univariate and multivariate logistic regression analysis. We included 182 consecutive patients treated with IVT in this study. HMCAS was present in 70 patients (38.5%). Patients with HMCAS had higher baseline National Institutes of Health Stroke Scale scores (p<0.001) and more frequent early ischaemic changes on baseline CT scan (p<0.001) than those without HMCAS. We identified 49 instances (26.9%) of HT in 182 follow-up CT scans. HMCAS was associated with HT in univariate analysis (unadjusted odds ratio [OR]=4.151, 95% confidence interval [CI]: 2.081-8.279, p<0.001) and remained an independent risk factor of HT in multivariate analysis (adjusted OR=2.691, 95% CI: 1.231-5.882, p=0.013). There was no statistically significant difference in the frequency of sICH between the HMCAS group and the non-HMCAS group. We concluded that HMCAS is common in anterior circulation infarction and is independently predictive of HT after thrombolytic therapy.
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July 2013

Predicting free choices for abstract intentions.

Proc Natl Acad Sci U S A 2013 Apr 18;110(15):6217-22. Epub 2013 Mar 18.

Bernstein Center for Computational Neuroscience, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany.

Unconscious neural activity has been repeatedly shown to precede and potentially even influence subsequent free decisions. However, to date, such findings have been mostly restricted to simple motor choices, and despite considerable debate, there is no evidence that the outcome of more complex free decisions can be predicted from prior brain signals. Here, we show that the outcome of a free decision to either add or subtract numbers can already be decoded from neural activity in medial prefrontal and parietal cortex 4 s before the participant reports they are consciously making their choice. These choice-predictive signals co-occurred with the so-called default mode brain activity pattern that was still dominant at the time when the choice-predictive signals occurred. Our results suggest that unconscious preparation of free choices is not restricted to motor preparation. Instead, decisions at multiple scales of abstraction evolve from the dynamics of preceding brain activity.
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April 2013

Tracking the unconscious generation of free decisions using ultra-high field fMRI.

PLoS One 2011 27;6(6):e21612. Epub 2011 Jun 27.

Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.

Recently, we demonstrated using functional magnetic resonance imaging (fMRI) that the outcome of free decisions can be decoded from brain activity several seconds before reaching conscious awareness. Activity patterns in anterior frontopolar cortex (BA 10) were temporally the first to carry intention-related information and thus a candidate region for the unconscious generation of free decisions. In the present study, the original paradigm was replicated and multivariate pattern classification was applied to functional images of frontopolar cortex, acquired using ultra-high field fMRI at 7 Tesla. Here, we show that predictive activity patterns recorded before a decision was made became increasingly stable with increasing temporal proximity to the time point of the conscious decision. Furthermore, detailed questionnaires exploring subjects' thoughts before and during the decision confirmed that decisions were made spontaneously and subjects were unaware of the evolution of their decision outcomes. These results give further evidence that FPC stands at the top of the prefrontal executive hierarchy in the unconscious generation of free decisions.
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November 2011