NISAN - the National Institute for Stroke and Applied Neurosciences
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Institute Director: Professor Valery Feigin
Deputy Director: Associate Professor Alice Theadom
The National Institute for Stroke and Applied Neurosciences (NISAN) conducts epidemiological studies and clinical trials to improve health and outcomes in people with major neurological disorders. Current research programmes focus on:
- Stroke
- Traumatic brain injury
- Neuromuscular disorders
- Neuroepidemiology
- Public health
- Neurorehabilitation
- Neuropsychology
- Biostatistics
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Recent Submissions
- ItemDiffering Definitions of First-Ever Stroke Influence Incidence Estimates More Than Trends: A Study Using Linked Administrative Data(S. Karger AG, 2023-09-26) Youens, David; Katzenellenbogen, Judith; Srinivasa Ragavan, Rathina; Sodhi-Berry, Nita; Carson, Jennie; Zemedikun, Dawit; Thrift, Amanda G; Feigin, Valery; Nedkoff, LeeIntroduction Researchers apply varying definitions when measuring stroke incidence using administrative data. We aimed to investigate the sensitivity of incidence estimates to varying definitions of stroke and lookback periods, and to provide updated incidence rates and trends for Western Australia (WA). Methods We used linked state-wide hospital and death data from 1985-2017 to identify incident strokes from 2005-2017. A standard definition was applied which included strokes coded as the principal hospital diagnosis or the underlying cause of death, with a 10-year lookback used to clear prevalent cases. Alternative definitions were compared against the standard definition by percentage difference in case numbers. Age-standardised incidence rates were calculated, and age- and sex-adjusted Poisson regression models used to estimate incidence trends. Results The standard definition with a 10-year lookback period captured 31,274 incident strokes. Capture increased by 19.3% when including secondary diagnoses, 4.1% when including nontraumatic subdural and extradural haemorrhage, and 8.1% when including associated causes of death. Excluding death records reduced capture by 11.1%. A 20-year lookback reduced over-ascertainment by 2.0% and a 1-year lookback increased capture by 13.3%. Incidence declined 0.6% annually (95% confidence interval -0.9, -0.3). Annual reductions were similar for most definitions except when death records were excluded (-0.1%, CI -0.4, 0.2) and with the shortest lookback periods (greatest annual reduction). Conclusion Stroke incidence has declined in WA. Differing methods of identifying stroke influence estimates of incidence to a greater extent than estimates of trends. Reductions in stroke incidence over time are primarily driven by declines in hospitalised stroke.
- ItemPrognostic Models for Global Functional Outcome and Post-concussion Symptoms Following Mild Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (Center-TBI) Study(Mary Ann Liebert Inc, 2023-08-16) Mikolić, A; Steyerberg, EW; Polinder, S; Wilson, L; Zeldovich, M; von Steinbueche, N; Newcombe, VFJ; Menon, DK; van der Naalt, J; Lingsma, HF; Maas, AIR; van Klaveren, D; Åkerlund, C; Amrein, K; Andelic, N; Andreassen, L; Anke, A; Antoni, A; Audibert, G; Azouvi, P; Azzolini, ML; Bartels, R; Barzó, P; Beauvais, R; Beer, R; Bellander, BM; Belli, A; Benali, H; Berardino, M; Beretta, L; Blaabjerg, M; Bragge, P; Brazinova, A; Brinck, V; Brooker, J; Brorsson, C; Buki, A; Bullinger, M; Cabeleira, M; Caccioppola, A; Calappi, E; Calvi, MR; Cameron, P; Carbayo Lozano, G; Carbonara, M; Cavallo, S; Chevallard, G; Chieregato, A; Citerio, G; Clusmann, H; Coburn, M; Coles, J; Cooper, JD; Correia, M; Čović, A; Curry, N; Czeiter, E; Czosnyka, M; Fizelier, CD; Dark, P; Dawes, H; De Keyser, V; Degos, V; Della Corte, F; den Boogert, H; Depreitere, B; Ðilvesi, Ð; Dixit, A; Donoghue, E; Dreier, J; Dulière, GL; Ercole, A; Esser, P; Ezer, E; Fabricius, M; Feigin, VL; Foks, K; Frisvold, S; Furmanov, A; Gagliardo, P; Galanaud, D; Gantner, D; Gao, G; George, P; Ghuysen, A; Giga, L; Glocker, B; Golubovic, J; Gomez, PA; Gratz, J; Gravesteijn, B; Grossi, F; Gruen, RL; Gupta, D; Haagsma, JA; Haitsma, I; Helbok, R; Helseth, E; Horton, L; Huijben, JAfter mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3–week post-concussion and mental health symptoms. Predictors were selected based on Akaike’s Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.
- ItemProposed Solutions to Anthropogenic Climate Change: A Systematic Literature Review and a New Way Forward(Elsevier BV, 2023) Feigin, Svetlana V; Wiebers, David O; Lueddeke, George; Morand, Serge; Lee, Kelley; Knight, Andrew; Brainin, Michael; Feigin, VL; Whitfort, Amanda; Marcum, James; Shackelford, Todd K; Skerratt, Lee F; Winkler, Andrea SHumanity is now facing what may be the biggest challenge to its existence: irreversible climate change brought about by human activity. Our planet is in a state of emergency, and we only have a short window of time (7–8 years) to enact meaningful change. The goal of this systematic literature review is to summarize the peer-reviewed literature on proposed solutions to climate change in the last 20 years (2002–2022), and to propose a framework for a unified approach to solving this climate change crisis. Solutions reviewed include a transition toward use of renewable energy resources, reduced energy consumption, rethinking the global transport sector, and nature-based solutions. This review highlights one of the most important but overlooked pieces in the puzzle of solving the climate change problem – the gradual shift to a plant-based diet and global phaseout of factory (industrialized animal) farming, the most damaging and prolific form of animal agriculture. The gradual global phaseout of industrialized animal farming can be achieved by increasingly replacing animal meat and other animal products with plant-based products, ending government subsidies for animal-based meat, dairy, and eggs, and initiating taxes on such products. Failure to act will ultimately result in a scenario of irreversible climate change with widespread famine and disease, global devastation, climate refugees, and warfare. We therefore suggest an “All Life” approach, invoking the interconnectedness of all life forms on our planet. The logistics for achieving this include a global standardization of Environmental, Social, and Governance (ESG) or similar measures and the introduction of a regulatory body for verification of such measures. These approaches will help deliver environmental and sustainability benefits for our planet far beyond an immediate reduction in global warming.
- ItemEthnic Differences in Stroke Outcomes in Aotearoa New Zealand: A National Linkage Study(SAGE Publications, 2023-03-05) Denison, Hayley; Corbin, Marine; Douwes, Jeroen; Thompson, Stephanie; Harwood, Matire; Davis, Alan; Fink, John N; Barber, P Alan; Gommans, John; Cadilhac, Dominique; Levack, William; McNaughton, Harry; Kim, Joosup; Feigin, VL; Abernethy, Virginia; Girvan, Jackie; Wilson, Andrew; Ranta, AnnemareiBACKGROUND: Ethnic differences in post-stroke outcomes have been largely attributed to biological and socioeconomic characteristics resulting in differential risk factor profiles and stroke sub-types, but evidence is mixed. AIMS: This study assessed ethnic differences in stroke outcome and service access in New Zealand (NZ) and explored underlying causes in addition to traditional risk factors. METHODS: This national cohort study used routinely collected health and social data to compare post-stroke outcomes between NZ Europeans, Māori, Pacific Peoples, and Asians, adjusting for differences in baseline characteristics, socioeconomic deprivation, and stroke characteristics. First and principal stroke public hospital admissions during November 2017-October 2018 were included (N=6,879). Post-stroke unfavourable outcome was defined as being dead, change in residence, or unemployed if working pre-stroke. RESULTS: In total, 5,394 NZ Europeans, 762 Māori, 369 Pacific Peoples and 354 Asians experienced a stroke during the study period. Median age was 65 years for Māori and Pacific Peoples, and 71 and 79 years for Asians and NZ Europeans, respectively. Compared with NZ Europeans, Māori were more likely to have an unfavourable outcome at all three time-points (OR=1.6 (95%CI=1.3-1.9); 1.4 (1.2-1.7); 1.4 (1.2-1.7), respectively). Māori also had increased odds of death at all time-points (1.7 (1.3-2.1); 1.5 (1.2-1.9); 1.7 (1.3-2.1)) and unemployment at twelve months (2.5 (1.2-5.2). There was evidence of differences in post-stroke secondary prevention medication by ethnicity. CONCLUSIONS: We found ethnic disparities in care and outcomes following stroke, independent of traditional risk factors raising concern for potential unconscious bias and institutional racism in stroke services.
- ItemComparative Effectiveness of Decompressive Craniectomy Versus Craniotomy for Traumatic Acute Subdural Hematoma (CENTER-TBI): An Observational Cohort Study(Elsevier BV, 2023) van Essen, TA; van Erp, IAM; Lingsma, HF; Pisică, D; Yue, JK; Singh, RD; van Dijck, JTJM; Volovici, V; Younsi, A; Kolias, A; Peppel, LD; Heijenbrok-Kal, M; Ribbers, GM; Menon, DK; Hutchinson, PJA; Manley, GT; Depreitere, B; Steyerberg, EW; Maas, AIR; de Ruiter, GCW; Peul, WC; Åkerlund, C; Amrein, K; Andelic, N; Andreassen, L; Anke, A; Antoni, A; Audibert, G; Azouvi, P; Azzolini, ML; Bartels, R; Barzó, P; Beauvais, R; Beer, R; Bellander, BM; Belli, A; Benali, H; Berardino, M; Beretta, L; Blaabjerg, M; Bragge, P; Brazinova, A; Brinck, V; Brooker, J; Brorsson, C; Buki, A; Bullinger, M; Cabeleira, M; Caccioppola, A; Calappi, E; Calvi, MR; Cameron, P; Lozano, GC; Carbonara, M; Castaño-León, AM; Cavallo, S; Chevallard, G; Chieregato, A; Citerio, G; Clusmann, H; Coburn, MS; Coles, J; Cooper, JD; Correia, M; Čović, A; Curry, N; Czeiter, E; Czosnyka, M; Dahyot-Fizelier, C; Dark, P; Dawes, H; De Keyser, V; Degos, V; Della Corte, F; Boogert, HD; Đilvesi, Đ; Dixit, A; Donoghue, E; Dreier, J; Dulière, GL; Ercole, A; Esser, P; Ezer, E; Fabricius, M; Feigin, VL; Foks, K; Frisvold, S; Furmanov, A; Gagliardo, P; Galanaud, D; Gantner, D; Gao, G; George, P; Ghuysen, A; Giga, L; Glocker, B; Golubović, J; Gomez, PA; Gratz, J; Gravesteijn, BBackground: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p < 0.0001). Higher centre preference for DC over craniotomy was not associated with better functional outcome (adjusted common odds ratio (OR) per 14% [IQR increase] more DC in a centre = 0.9 [95% CI 0.7–1.1], n = 200). Primary DC was associated with more follow-on surgeries and complications [secondary cranial surgery 27% vs. 18%; shunts 11 vs. 5%]; and similar odds of in-hospital mortality (adjusted OR per 14% IQR more primary DC 1.3 [95% CI (1.0–3.4), n = 200]). Interpretation: We found substantial practice variation in the employment of DC over craniotomy for ASDH. This variation in treatment strategy did not result in different functional outcome. These findings suggest that primary DC should be restricted to salvageable patients in whom immediate replacement of the bone flap is not possible due to intraoperative brain swelling. Funding: Hersenstichting Nederland for the Dutch NeuroTraumatology Quality Registry and the European Union Seventh Framework Program.