NISAN - the National Institute for Stroke and Applied Neurosciences
Permanent link for this collectionhttps://hdl.handle.net/10292/10244
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
Item Burden of 375 Diseases and Injuries, Risk-Attributable Burden of 88 Risk Factors, and Healthy Life Expectancy in 204 Countries and Territories, Including 660 Subnational Locations, 1990–2023: A Systematic Analysis for the Global Burden of Disease Study 2023(Elsevier, 2025) GBD 2023 Disease and Injury and Risk Factor Collaborators; Feigin, ValeryItem Global Age-Sex-Specific All-Cause Mortality and Life Expectancy Estimates for 204 Countries and Territories and 660 Subnational Locations, 1950–2023: A Demographic Analysis for the Global Burden of Disease Study 2023(Elsevier, 2025) GBD 2023 Demographics Collaborators; Feigin, ValeryItem Global Burden of 292 Causes of Death in 204 Countries and Territories and 660 Subnational Locations, 1990–2023: A Systematic Analysis for the Global Burden of Disease Study 2023(Elsevier BV, 2025) GBD 2023 Causes of Death Collaborators; Feigin, ValeryItem Global, Regional, and National Burden of Headache Disorders, 1990–2021, With Forecasts to 2050: A Global Burden of Disease Study 2021(Elsevier, 2025) GBD 2021 Headache Collaborators. Electronic address: yonkkang@gmail.com; Wijeratne, Tissa; Oh, Jiyeon; Kim, Soeun; Yim, Yesol; Kim, Min Seo; Shin, Jae Il; Oh, Yun-Seo; Jung, Raon; Kim, Yun Seo; Smith, Lee; Aalruz, Hasan; Abd-Rabu, Rami; Abdulah, Deldar Morad; Aboagye, Richard Gyan; Abolmaali, Meysam; Abtahi, Dariush; Abualhasan, Ahmed; Adedoyin, Rufus Adesoji; Adnani, Qorinah Estiningtyas Sakilah; Afrashteh, Fatemeh; Aggarwal, Navidha; Ahmad, Danish; Ahmadi, Ali; Ahmadi, Negar Sadat; Ahmadzade, Amir Mahmoud; Ahmed, Syed Anees; Al Awaidy, Salah; Alabbad, Sawsan; Alajlani, Muaaz M; Al-Ajlouni, Yazan; Ali, Mohammed Usman; Ali, Syed Shujait; Ali, Waad; Almazan, Joseph Uy; Alshahrani, Najim Z; Altaf, Awais; Al-Wardat, Mohammad; Alzoubi, Karem H; Amiri, Sohrab; Amu, Hubert; Amusa, Ganiyu Adeniyi; Anderson, David B; Anwar, Saleha; Areda, Demelash; Asghari-Jafarabadi, Mohammad; Ashina, Sait; Ashraf, Javed; Ashraf, Tahira; Azargoonjahromi, Ali; Bahurupi, Yogesh; Baig, Atif Amin; Bandyopadhyay, Soham; Bardhan, Mainak; Barqawi, Hiba Jawdat; Bashiri, Azadeh; Bastan, Mohammad-Mahdi; Bemanalizadeh, Maryam; Bensenor, Isabela M; Berhie, Alemshet Yirga Yirga; Bhagavathula, Akshaya Srikanth; Bhaskar, Sonu; Bhat, Vivek; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh; Bilgin, Cem; Biswas, Atanu; Bizzozero-Peroni, Bruno; Bustanji, Yasser; Cámera, Luis Alberto; Caronna, Edoardo; Carvalho, Andre F; Chakraborty, Sandip; Ching, Patrick R; Christodoulou, Nikos; Chu, Dinh-Toi; Chu, Hongyuan; Cruz-Martins, Natalia; Dadras, Omid; Dai, Xiaochen; D'Amico, Emanuele; Darwish, Amira Hamed; Deekonda, Sindhura; Devanbu, Vinoth Gnana Chellaiyan; Dharmaratne, Samath Dhamminda; Dima, Adriana; Dinkayehu, Temesgien Ergetie; Do, Huyen; Doku, Paul Narh; Doshi, Ojas Prakashbhai; E'mar, Abdel Rahman; Eissazade, Negin; Eltaha, Chadi; Fahim, Ayesha; Fares, Jawad; Farjoud Kouhanjani, Mohsen; Faro, Andre; Fazeli, Patrick; Fereshtehnejad, Seyed-Mohammad; Ferrara, Pietro; Ferreira, Nuno; Fischer, Florian; Fornari, Arianna; Gajdács, Márió; Gebregergis, Miglas Welay; Ghadimi, Delaram J; Ghaffari Jolfayi, Amir; Gnedovskaya, Elena V; Golechha, Mahaveer; Gomez Figueroa, Enrique; Hashempur, Mohammad Hashem; Hasnain, Md Saquib; Hassan, Amr; Hassan, Nageeb; Hassan Zadeh Tabatabaei, Mahgol Sadat; Hegazy, Mohamed I; Heidari, Golnaz; Helfer, Bartosz; Hossain, Md Mahbub; Househ, Mowafa; Hu, Chengxi; Iavicoli, Ivo; Ilesanmi, Olayinka Stephen; Ilic, Irena M; Ilyas, Muhana Fawwazy; Ilyasu, Salim; Ismail, Nahlah Elkudssiah; Jafari-Khounigh, Ali; Jahrami, Haitham; Janodia, Manthan Dilipkumar; Jayasinghe, Ruwan Duminda; Jeswani, Bijay Mukesh; Jonas, Jost B; Joseph, Nitin; Kalani, Rizwan; Khan, Moien AB; Khateri, Sorour; Khatib, Mahalaqua Nazli; Khayat Kashani, Hamid Reza; Khidri, Feriha Fatima; Khormali, Moein; Khosravi, Sepehr; Kim, Yun Jin; Kompani, Farzad; Kostev, Karel; Krishan, Kewal; Krishnan, Bindu; Defo, Barthelemy Kuate; Kuddus, Mohammed; Kulimbet, Mukhtar; Kumar, Rakesh; Kumar, Vijay; Kytö, Ville; Lasrado, Savita; Lee, Seung Won; Lenzi, Jacopo; Leonardi, Matilde; Lucchetti, Giancarlo; Lugo, Alessandra; Makhdoom, Irsa Fatima; Mallahzadeh, Arashk; Mansouri, Vahid; Marzo, Roy Rillera; Mathangasinghe, Yasith; Mayeli, Mahsa; Mehmood, Asim; Meretoja, Atte; Mestrovic, Tomislav; Mettananda, Sachith; Minervini, Giuseppe; Mishra, Archana; Mithra, Prasanna; Mohamed Ahmed, Khabab Abbasher Hussien; Mohammadzadeh, Ibrahim; Mohammed, Shafiu; Monasta, Lorenzo; Morrison, Shane Douglas; Nabavi, Amin; Natto, Zuhair S; Nauman, Javaid; Nieddu, Luciano; Nugen, Fred; Olagunju, Andrew T; Oliveira, Arão Belitardo; Oliveira, Welber Sousa; Omar, Hany A; Omer, Goran Latif; Otstavnov, Nikita; P A, Mahesh; Panos, Leonidas D; Parikh, Romil R; Patil, Shankargouda; Patra, Apurba; Pedersini, Paolo; Pensato, Umberto; Peprah, Prince; Peres, Mario FP; Piradov, Michael A; Pozo-Rosich, Patricia; Pradhan, Jalandhar; Prakash, Sanjay; Prashant, Akila; Puvvula, Jagadeesh; Rafiei, Alireza; Raggi, Alberto; Rahmani, Amir Masoud; Ramadan, Mahmoud Mohammed; Rathish, Devarajan; Rautalin, Ilari; Rawaf, Salman; Rezaeian, Mohsen; Rezazadeh Eidgahi, Donya; Rhee, Taeho Gregory; Roy, Priyanka; Saad Eddin, Adnan; Sabet, Cameron John; Saddik, Basema Ahmad; Sadeghi, Erfan; Saeed, Umar; Saheb Sharif-Askari, Fatemeh; Saheb Sharif-Askari, Narjes; Sahoo, Pragyan Monalisa; Salimi, Sohrab; Samy, Abdallah M; Saulam, Jennifer; Sawhney, Monika; Senol, Yigit Can; Senthilkumaran, Subramanian; Sethi, Yashendra; Seyedmirzaei, Homa; Shafie, Mahan; Shamsi, Anas; Sharifan, Amin; Shehata, Hatem Samir; Shenoy, Rekha Raghuveer; Shokraneh, Farhad; Sidhu, Jaspreet Kaur; Singh, Baljinder; Singh, Harmanjit; Singh, Jasvinder A; Singh, Surjit; Skryabina, Anna Aleksandrovna; Sobia, Farrukh; Srichawla, Bahadar S; Suresh, Vinay; Swain, Chandan Kumar; T Y, Sree Sudha; Tabaee Damavandi, Payam; Tabche, Celine; Tabish, Mohammad; Tanwar, Manoj; Temsah, Mohamad-Hani; Teramoto, Masayuki; Tran, Nghia Minh; Tran, Thang Huu; Tsatsakis, Aristidis; Udoakang, Aniefiok John; Usman, Jibrin Sammani; Uzunçıbuk, Hande; Van den Eynde, Jef; Vasankari, Tommi Juhani; Venketasubramanian, Narayanaswamy; Villafañe, Jorge Hugo; Wang, Lintao; Wang, Xingxin; Wang, Yuan-Pang; Wiangkham, Taweewat; Winkler, Andrea Sylvia; Wollie, Alemayehu Molla; Xiao, Zheman; Yismaw, Yazachew Engida Engida; Yousuf, Abdilahi; Zhao, Zhongyi; Zielińska, Magdalena; Chu, Min Kyung; Song, Tae-Jin; Yon, Dong Keon; Feigin, Valery LHeadache disorders, especially migraines and tension-type headaches (TTHs), are major global public health concerns, as shown by the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. We provide updated global estimates of prevalence and years lived with disability (YLDs) from 1990 to 2021 across 204 countries and territories and forecasts through 2050. In 2021, there are 2.0 billion people with TTH and 1.2 billion with migraine. Although TTH is more prevalent, migraine causes higher disability. While crude prevalence and YLDs increased, age-standardized rates remained stable and are projected to continue this trend due to population growth. There is a disproportionately higher burden in women aged 30-44 and countries with higher Socio-demographic Index and Healthcare Access and Quality Index. Despite this, migraines remain underrecognized in health policies and funding. This study emphasizes the urgent need to prioritize headache disorders in global health agendas.Item Preventing Stroke Research Priorities Project: An Initiative of Synergies to Prevent Stroke (STOPstroke)(Wiley, 2025-09-18) Gall, Seana; Farmer, Christine; Kitsos, Gemma; Rehman, Sabah; Phan, Hoang; Barker, Seamus; Booth, Brenda; Thrift, Amanda; Katzenellenbogen, Judith; Nelson, Mark; Kleinig, Timothy; Feigin, Valery; Cadilhac, Dominique; Nedkoff, Lee; Kim, Joosup; Kilkenny, MoniqueBackground: Research priority setting projects provide a method to engage stakeholders in the prioritisation of research activities. We conducted a priority setting project to identify priorities for research into the primary and secondary prevention of stroke. Methods: A modified James Lind Alliance method was used for this project undertaken in Australia and New Zealand with two online surveys (September–November 2021 and May-June 2022) and an online workshop (August 2022). The main question addressed was ‘What question about preventing stroke would you like to see answered by researchers?’ Responses to Survey 1 were refined and reviewed to identify evidence uncertainties. Questions with uncertain evidence were presented in Survey 2 where participants rated the importance of questions. Quantitative analysis of the importance ratings identified highly rated questions. These questions were taken to the online workshop with two rounds of facilitated discussion to create a final list of priorities. A postworkshop evaluation questionnaire explored user’s perceptions of the process. Results: In Survey 1, 375 people proposed > 700 research questions. These were refined to 134 questions that were checked against evidence with 47 determined to be unanswered and distributed for consideration in Survey 2. Respondents to Survey 2 (n = 97) rated 24 of the 47 questions highly that were then discussed in the online workshop (n = 16 participants). There was agreement on the most highly rated question ‘How can we improve early detection and measurement of stroke risk?’ but limited agreement on the remaining questions. Participants favoured keeping all questions but presenting them thematically. The final list includes 22 questions under behavioural; pharmacological/clinical; structural; policy; individual; population and secondary prevention themes. Participants rated the workshop experience as acceptable. Conclusion: A suite of research priorities for the primary and secondary prevention of stroke were identified by a broad range of stakeholders including people with lived experience of stroke, the public and health professionals.Item Polypill and RiskOMeter to Prevent StrOke and CogniTive ImpairmEnt in Primary Health Care (PROMOTE) Randomized Clinical Trial: Rationale and Design(S. Karger AG, 2025-08-23) Brainin, Michael; Anderson, Craig S; Bath, Philip M; Hankey, Graeme J; Sposato, Luciano A; Pille, Arthur; Pontes-Neto, Octávio Marques; Sampaio Silva, Gisele; Nasi, Luiz Antonio; Souza, Diogo O; Feigin, Valery L; Lopes, Renato D; Berwanger, Otávio; Pires, Aline Palmeira; Secchi, Thaís Leite; Teló, Brunna Jaeger; Santos, Franciele P; Radin, Jaqueline; Ellwanger, Juliana; Martins, Magda Ouriques; Pereira, Danielle A; Quadros, Francine W; Silva, Larissa Vitoria; Gonçalves, Marcelo Rodrigues; Mantovani, Gabriel Paulo; Ceretta, Manoela; Bastianello, João Eduardo; Andrade, Guilherme B; Schirmer, Caroline; Zimmer, Aline R; Zimmer, Eduardo R; Rodrigues, Márcio; Falavigna, Maicon; Martins, Sheila Ouriques; World Stroke Organization’s Cut Stroke in Half ProjectINTRODUCTION: Stroke and dementia have common modifiable risk factors. Current prevention strategies primarily focus on high-risk populations, leaving a gap in addressing the broader population. We report the protocol for a randomized controlled trial (RCT) that aims to evaluate the feasibility, tolerability, and effectiveness of a polypill (valsartan 80mg, amlodipine 5mg, and rosuvastatin 10mg), with and without use of the Stroke Riskometer app, on systolic blood pressure (SBP) and other cardiovascular disease (CVD) risk factors at 9 months after randomization in a population of low to borderline CVD risk. METHODS: Prospective, pragmatic, multicentre, factorial, phase III, placebo-controlled, cluster RCT in low to moderate CVD risk (10-year risk <20%) individuals aged 50-75 years with no prior history of hypertension, diabetes mellitus, stroke, or other CVD, with a SBP of 121-139 mmHg and at least one lifestyle-related CVD risk factor. Primary Care Units in Porto Alegre, Brazil, were centrally randomized to either use of the Stroke Riskometer app or standard care for lifestyle modification. All eligible individuals underwent a 28-day open run-in phase using the active medication. Participants who tolerated and had high adherence were randomized to either polypill or placebo, using a minimization process according to age, sex, SBP, cholesterol, and education level. The dual primary outcomes were change in SBP and Life Simple 7 (LS7) score at 9 months post-randomization. A sample of 354 participants was estimated to provide 80% statistical power (two sided α=0.05, β =0.20) for 6 clusters with intra-cluster correlation of 0.01 to detect a clinically significant 2.5 mmHg (SD±8) difference in SBP change and 0.65 points (SD±1.61) difference in the LS7 score at 9 months post-randomization between the polypill/Stroke Riskometer group and placebo/usual care group, assuming 10% lost to follow-up. All analyses were conducted according to the intention-to-treat principle. Regression analysis models (ANCOVA) assessed the differences among the four groups concerning changes in SBP, cholesterol levels, cognitive function, and behavioral risk factors over time. CONCLUSION: The findings will provide critical information to allow the development of primary stroke and CVD prevention strategies in low to borderline CVD risk adults. The trial is registered at clinicaltrials.gov NCT05155137.Item Differences Between Men and Women in Treatment and Outcome After Traumatic Brain Injury(Mary Ann Liebert Inc, 2021) Mikolic, A; Klaveren, DV; Groeniger, JO; Wiegers, EJA; Lingsma, HF; Zeldovich, M; Steinbüchel, NV; Maas, AIR; Lennep, JERV; Polinder, S; 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; Monza, AD; Ceyisakar, I; Clusmann, H; Coburn, M; Coles, J; Cooper, JD; Correia, M; Čović, A; Curry, N; Czeiter, E; Czosnyka, M; Dahyot-Fizelier, C; Dark, P; Dawes, H; Keyser, VD; Degos, V; Corte, FD; Boogert, HD; Depreitere, B; 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; Ghuysne, 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; Jones, K; Theadom, ATraumatic brain injury (TBI) is a significant cause of disability, but little is known about sex and gender differences after TBI. We aimed to analyze the association between sex/gender, and the broad range of care pathways, treatment characteristics, and outcomes following mild and moderate/severe TBI. We performed mixed-effects regression analyses in the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, stratified for injury severity and age, and adjusted for baseline characteristics. Outcomes were various care pathway and treatment variables, and 6-month measures of functional outcome, health-related quality of life (HRQoL), post-concussion symptoms (PCS), and mental health symptoms. The study included 2862 adults (36% women) with mild (mTBI; Glasgow Coma Scale [GCS] score 13-15), and 1333 adults (26% women) with moderate/severe TBI (GCS score 3-12). Women were less likely to be admitted to the intensive care unit (ICU; odds ratios [OR] 0.6, 95% confidence interval [CI]: 0.4-0.8) following mTBI. Following moderate/severe TBI, women had a shorter median hospital stay (OR 0.7, 95% CI: 0.5-1.0). Following mTBI, women had poorer outcomes; lower Glasgow Outcome Scale Extended (GOSE; OR 1.4, 95% CI: 1.2-1.6), lower generic and disease-specific HRQoL, and more severe PCS, depression, and anxiety. Among them, women under age 45 and above age 65 years showed worse 6-month outcomes compared with men of the same age. Following moderate/severe TBI, there was no difference in GOSE (OR 0.9, 95% CI: 0.7-1.2), but women reported more severe PCS (OR 1.7, 95% CI: 1.1-2.6). Men and women differ in care pathways and outcomes following TBI. Women generally report worse 6-month outcomes, but the size of differences depend on TBI severity and age. Future studies should examine factors that explain these differences.Item A Double-blind, Placebo-controlled, Randomized, Multi-centre, Phase III Study of MLC901 (NeuroAiDTMII) for the Treatment of Cognitive Impairment After Mild Traumatic Brain Injury(Public Library of Science (PLoS), 2025-07-10) Pilipenko, PI; Ivanova, AA; Kotsiubinskaya, YV; Grigoryeva, VN; Khrulev, AY; Skorokhodov, AV; Gavrik, MM; Mkrtchan, NN; Majdan, M; Valkovic, P; Rabarova, D; Barker-Collo, S; Jones, K; Feigin, VLIntroduction About half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. Although up to 40% of adults with mild TBI experience persistent functional deficits, there is no proven-effective treatment to facilitate recovery after it. Methods and analysis This randomized placebo-controlled multi-centre study was aimed to examine the efficacy of herbal supplement MLC901 on complex attention following mild TBI at 6 months post-randomisation, as a primary outcome measured by CNS Vital signs (CNS-VS). Adults aged 18–65 years, who were 1–12-months post-mild TBI and experienced cognitive impairment, were randomly assigned to receive either MLC901 two capsules (0.4g/capsule) or placebo three times a day for 6 months using centralized stratified permuted block randomization. Secondary outcomes: Rivermead Post-Concussion Symptoms Questionnaire (RPQ; neurobehavioral sequelae); Health Related Quality of Life (QOLIBRI); Hospital Anxiety and Depression Scale (HADS); and safety. Mixed effects models of repeated measures with intention to treat analysis were employed. A Least Square Mean Difference (LSMD) from baseline to 3-, 6-, and 9-month follow-up was calculated with 95% confidence intervals (CI). Results In the analysis, 182 participants (47.8% females) were included. Multivariable mixed effects model analysis did not reveal significant improvements in complex attention (LSMD = −1.18 [95% CI −5.40; 3.03; p = 0.58]) and other cognitive domains at 6 months in the MLC901 group compared to the Placebo group. There were significant improvements in RPQ, QOLIBRI, anxiety and depression in the MLC901 group compared to the Placebo group at 6 and 9 months (LSMD −4.36 [−6.46; −2.26] and −4.07 [−6.22; −1.92], 4.84 [1.58; 8.10] and 3.74 [0.44; 7.03], −1.50 [−2.29; −0.71 and −0.96 [−1.84; −0.08], −1.14 [−1.92; −0.35] and −1.14 [−1.94; −0.34]), respectively. MLC901 tested was proven safe. Conclusions Although the 6-month treatment with MLC901 did not result in a statistically significant difference with placebo for CNS-VS measurement of cognitive domains in individuals with mild TBI, the study showed a clinically and statistically significant improvement in all clinical scales assessed by the investigators.Item Characterising Acute and Chronic Care Needs: Insights from the Global Burden of Disease Study 2019(Springer Science and Business Media LLC, 2025) Zuniga, YMH; Zumla, A; Zuhlke, LJ; Zoladl, M; Ziaeian, B; Zhong, C; Zhao, XJG; Zhang, ZJ; Zhang, J; Zepro, NB; Zenebe, GA; Zeitoun, JD; Zegeye, ZB; Zastrozhin, MS; Zareshahrabadi, Z; Zarea, K; Dehnavi, AZ; Zare, I; Zangiabadian, M; Zangeneh, A; Zamora, N; Zaman, SB; Zaki, N; Zakaryaei, F; Zahir, M; Tajrishi, FZ; Zadnik, V; Zadey, S; Yusefi, H; Yousefinezhadi, T; Yousefi, Z; Younis, MZ; You, Y; Yonemoto, N; Yon, DK; Yisihak, E; Yip, P; Yiğit, V; Yiğit, A; Yi, S; Ye, P; Yazdanpanah, F; Yaya, S; Yano, Y; Yang, L; Yamagishi, K; Yamada, T; Jabbari, SHY; Yahya, GATY; Yaghoubi, S; Xu, X; Xu, S; Xu, H; Xie, Y; Xiao, H; Wulandari, RDWI; Wubetie, GA; Wu, AM; Woolf, AD; Wolfe, CDA; Woldemariam, M; Tsadik, DSW; Woday, AT; Wickramasinghe, ND; Wiangkham, T; Westerman, R; Wen, YF; Wei, MY; Waris, A; Ward, P; Wang, Z; Wang, YP; Wang, Y; Wang, Y; Vu, LG; Volovici, V; Vo, B; Vlassov, V; Vishwanath, PM; Violante, FS; Villafañe, JH; Vervoort, D; Veroux, M; Verma, M; Venketasubramanian, N; Vaziri, S; Vasic, M; Vasankari, TJ; Varughese, S; Vart, P; Varma, RP; Vardavas, C; Van den Eynde, J; Valizadeh, R; Valdez, PR; Tahbaz, SV; Vakilian, A; Vacante, M; Upadhyay, E; Unnikrishnan, BChronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic care, while 27% were due to acute care. Chronic care needs increased with age, representing 86% of YLDs and 71% of YLLs, and accounting for 93% of YLDs from sequelae. These findings highlight that chronic care needs far exceed acute care needs globally, necessitating health systems to adapt accordingly.Item Estimating Normal and Reference Pulse Wave Velocity in New Zealand Population(Informa UK Limited, 2025-06-23) Dahiya, Ekta; Lowe, A; Krishnamurthi, R; Anand, Gautam; Kalra, AnubhaThis study aimed to establish normal and reference pulse wave velocity (PWV) values and assess their relationship with the established cardiovascular risk factors in NZ. An observational cross-sectional study of 120 adults above 18 years was conducted at Auckland University of Technology within three age groups (18-30, 31-60, and >60 years) and four blood pressure (BP) categories (normal, elevated, stage 1 and stage 2) before being clustered as Normal Value Population (NVP) and Reference Value Population (RVP) based on BP and presence of other CVD risk. PWV was measured using Doppler ultrasound via the direct carotid-femoral method (distance × 0.8). Mean PWV for the whole study population was 5.88 ± 1.49 m/s and increased with age (p < 0.001) and with a more profound rise in the RVP group (p < 0.001, z = -4.98). Overall PWV values were lower than international reference standards, which may reflect population-specific physiological or methodological factors. A significant difference in mean PWV in the European and non-European populations (p = 0.004) indicated that ethnicity was an important part of the assessment. Age and mean blood pressure were the strongest predictors of PWV, accounting for 54.5% of the variability.Item Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage: The Global Burden of Disease Study 2021.(American Medical Association, 2025) GBD 2021 Global Subarachnoid Hemorrhage Risk Factors Collaborators; Rautalin, Ilari; Volovici, Victor; Stark, Benjamin A; Johnson, Catherine O; Kaprio, Jaakko; Korja, Miikka; Krishnamurthi, Rita V; Nair, Balakrishnan Sukumaran; Ranta, Annemarei; Rinkel, Gabriel JE; Vergouwen, Mervyn DI; Abate, Yohannes Habtegiorgis; Abbastabar, Hedayat; Abd-Allah, Foad; Abdelkader, Atef; Abdi, Parsa; Abdollahi, Arash; Abdullahi, Auwal; Abiodun, Olugbenga Olusola; Aboagye, Richard Gyan; Abouzid, Mohamed; Abtahi, Dariush; Abu Rumeileh, Samir; Abualhasan, Ahmed; Abualruz, Hasan; Abukhadijah, Hana J; Abu-Zaid, Ahmed; Adamu, Lawan Hassan; Addo, Isaac Yeboah; Adedoyin, Rufus Adesoji; Adegboye, Oyelola A; Adra, Saryia; Adzigbli, Leticia Akua; Agyemang-Duah, Williams; Ahinkorah, Bright Opoku; Ahmad, Aqeel; Ahmad, Danish; Ahmadzade, Amir Mahmoud; Ahmed, Ali; Ahmed, Haroon; Ahmed, Syed Anees; Aji, Budi; Akkaif, Mohammed Ahmed; Al-Ajlouni, Yazan; Al-Aly, Ziyad; Albashtawy, Mohammed; Ali, Mohammed Usman; Alif, Sheikh Mohammad; Alimohamadi, Yousef; Aljunid, Syed Mohamed; Alomari, Mahmoud A; Alrawashdeh, Ahmad; Alsabri, Mohammed A; Salman, Rustam Al-Shahi; Altaf, Awais; Al-Tammemi, Alaa B; Alvis-Guzman, Nelson; Alwafi, Hassan; Al-Wardat, Mohammad; Al-Worafi, Yaser Mohammed; Aly, Hany; Alyahya, Mohammad Sharif Ibrahim; Alzoubi, Karem H; Amani, Reza; Amin, Tarek Tawfik; Amindarolzarbi, Alireza; Amusa, Ganiyu Adeniyi; Anderlini, Deanna; Angappan, Dhanalakshmi; Anil, Abhishek; Anuoluwa, Boluwatife Stephen; Anwar, Saleha; Anyasodor, Anayochukwu Edward; Apostol, Geminn Louis Carace; Arabloo, Jalal; Areda, Demelash; Ärnlöv, Johan; Artamonov, Anton A; Artanti, Kurnia Dwi; Arumugam, Ashokan; Aryan, Zahra; Asghari-Jafarabadi, Mohammad; Ashemo, Mubarek Yesse; Ashraf, Tahira; Athar, Mohammad; Athari, Seyyed Shamsadin; Aujayeb, Avinash; Awotidebe, Adedapo Wasiu; Azadnajafabad, Sina; Aziz, Shahkaar; Azzam, Ahmed Y; Babu, Giridhara Rathnaiah; Bagheri, Nasser; Bahrami Taghanaki, Pegah; Bahramian, Saeed; Bai, Ruhai; Baig, Atif Amin; Bako, Abdulaziz T; Baltatu, Ovidiu Constantin; Bam, Kiran; Banach, Maciej; Bandyopadhyay, Soham; Banik, Biswajit; Bardhan, Mainak; Barker-Collo, Suzanne Lyn; Bärnighausen, Till Winfried; Barqawi, Hiba Jawdat; Barua, Lingkan; Bastan, Mohammad-Mahdi; Basu, Sanjay; Bell, Shelly L; Bensenor, Isabela M; Berhie, Alemshet Yirga; Beyene, Kebede A; Bhagavathula, Akshaya Srikanth; Bhaskar, Sonu; Bhat, Ajay Nagesh; Bhat, Vivek; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh; Bijani, Ali; Bikbov, Boris; Birhan, Mekuriaw Mesfin; Birhanu, Mulugeta M; Bitra, Veera R; Boloor, Archith; Borhany, Hamed; Breitner, Susanne; Brenner, Hermann; Bugiardini, Raffaele; Bulamu, Norma B; Butt, Zahid A; Cabral, Lucas Scotta; Caetano Dos Santos, Florentino Luciano; Calina, Daniela; Cámera, Luis Alberto; Campos, Luciana Aparecida; Campos-Nonato, Ismael; Capodici, Angelo; Carvalho, Felix; Castañeda-Orjuela, Carlos A; Catapano, Alberico L; Cegolon, Luca; Chadwick, Joshua; Chakraborty, Chiranjib; Chakraborty, Promit Ananyo; Chakraborty, Sandip; Chandika, Rama Mohan; Chanie, Gashaw Sisay; Chattu, Vijay Kumar; Chaudhary, Anis Ahmad; Chi, Gerald; Chichagi, Fatemeh; Ching, Patrick R; Chopra, Hitesh; Choudhari, Sonali Gajanan; Chowdhury, Enayet Karim; Chu, Dinh-Toi; Chung, Sheng-Chia; Columbus, Alyssa; Criqui, Michael H; da Silva, Alanna Gomes; Dabbagh Ohadi, Mohammad Amin; Dadras, Omid; Dai, Xiaochen; Dalal, Koustuv; Dalli, Lachlan L; D'Amico, Emanuele; Dashti, Mohsen; Davletov, Kairat; De la Cruz-Góngora, Vanessa; Debopadhaya, Shayom; Delgado-Enciso, Ivan; Derviševic, Emina; Devanbu, Vinoth Gnana Chellaiyan; Dewan, Syed Masudur Rahman; Dhane, Amol S; Dibas, Mahmoud; Do, Thanh Chi; Do, Thao Huynh Phuong; Dohare, Sushil; Doheim, Mohamed Fahmy; Dokova, Klara Georgieva; Dongarwar, Deepa; D'Oria, Mario; Doshi, Ojas Prakashbhai; Doshi, Rajkumar Prakashbhai; Dowou, Robert Kokou; Dsouza, Haneil Larson; Dutta, Siddhartha; Dziedzic, Arkadiusz Marian; E'mar, Abdel Rahman; Edvardsson, David; Efendi, Defi; Efendi, Ferry; El Nahas, Nevine; Elgendy, Islam Y; Elhadi, Muhammed; Eltaha, Chadi; Eltahir, Mohd Elmagzoub; Emeto, Theophilus I; Fabin, Natalia; Fagbamigbe, Adeniyi Francis; Fahim, Ayesha; Fakhradiyev, Ildar Ravisovich; Fares, Jawad; Faris, Pawan Sirwan; Fauk, Nelsensius Klau; Fazylov, Timur; Fekadu, Ginenus; Ferreira, Nuno; Fetensa, Getahun; Fischer, Florian; Foschi, Matteo; Fridayani, Ni Kadek Yuni; Gaipov, Abduzhappar; Gajjar, Avi A; Gandhi, Aravind P; Ganesan, Balasankar; Garg, Ravindra Kumar; Gebregergis, Miglas Welay; Gebrehiwot, Mesfin; Gebremeskel, Teferi Gebru; Getie, Molla; Ghadimi, Delaram J; Ghadirian, Fataneh; Ghahramani, Sulmaz; Ghasemzadeh, Afsaneh; Ghazy, Ramy Mohamed; Gholamalizadeh, Maryam; Ghozy, Sherief; Gil, Artyom Urievich; Gilani, Jaleed Ahmed; Gnedovskaya, Elena V; Goleij, Pouya; Goulart, Alessandra C; Goulart, Barbara Niegia Garcia; Guan, Shi-Yang; Gupta, Sapna; Habibzadeh, Farrokh; Hadei, Mostafa; Hadi, Najah R; Hamidi, Samer; Hanifi, Nasrin; Hankey, Graeme J; Harlianto, Netanja I; Haro, Josep Maria; Hasan, Faizul; Hasani, Hamidreza; Hasnain, Md Saquib; Hassan Zadeh Tabatabaei, Mahgol Sadat; Haubold, Johannes; Havmoeller, Rasmus J; Hay, Simon I; Hbid, Youssef; Heidari, Golnaz; Heidari, Mohammad; Hemmati, Mehdi; Hiraike, Yuta; Hoan, Nguyen Quoc; Holla, Ramesh; Hosseinzadeh, Mehdi; Hostiuc, Sorin; Huang, Junjie; Huynh, Hong-Han; Hwang, Bing-Fang; Ibitoye, Segun Emmanuel; Ikeda, Nayu; Ikiroma, Adalia; Ilaghi, Mehran; Ilesanmi, Olayinka Stephen; Ilic, Irena M; Ilic, Milena D; Islam, Md Rabiul; Ismail, Nahlah Elkudssiah; Iso, Hiroyasu; Isola, Gaetano; Iwagami, Masao; Jacob, Louis; Jafarzadeh, Abdollah; Jain, Akhil; Jairoun, Ammar Abdulrahman; Jakovljevic, Mihajlo; Jatau, Abubakar Ibrahim; Jawaid, Talha; Jayapal, Sathish Kumar; Jonas, Jost B; Joseph, Nitin; Jürisson, Mikk; Kadashetti, Vidya; Kalani, Rizwan; Kamal, Vineet Kumar; Kamireddy, Arun; Kanchan, Tanuj; Kandel, Himal; Karami, Jafar; Karaye, Ibraheem M; Karimi, Yeganeh; Karimi Behnagh, Arman; Kashoo, Faizan Zaffar; Kayode, Gbenga A; Kazemi, Foad; Kesse-Guyot, Emmanuelle; Khader, Yousef Saleh; Khaing, Inn Kynn; Khan, Fayaz; Khan, Mohammad Jobair; Khatatbeh, Haitham; Khatatbeh, Moawiah Mohammad; Khayat Kashani, Hamid Reza; Kheirallah, Khalid A; Khidri, Feriha Fatima; Khormali, Moein; Khosla, Atulya Aman; Kim, Kwanghyun; Kim, Yun Jin; Kisa, Adnan; Kisa, Sezer; Kivimäki, Mika; Kolahi, Ali-Asghar; Kompani, Farzad; Korzh, Oleksii; Kostev, Karel; Kothari, Nikhil; Krishan, Kewal; Krishna, Varun; Krishnamoorthy, Vijay; Kuddus, Mohammed; Kulimbet, Mukhtar; Kunutsor, Setor K; Kurniasari, Maria Dyah; Kusuma, Dian; Kytö, Ville; La Vecchia, Carlo; Lahariya, Chandrakant; Lai, Daphne Teck Ching; Lai, Hanpeng; Laksono, Tri; Lallukka, Tea; Latief, Kamaluddin; Latifinaibin, Kaveh; Le, Nhi Huu Hanh; Le, Thao Thi Thu; Lee, Munjae; Lee, Seung Won; Lee, Wei-Chen; Lee, Yo Han; Lenzi, Jacopo; Leonardi, Matilde; Li, Ming-Chieh; Li, Xiaopan; Lim, Stephen S; Lin, Jialing; Liu, Xuefeng; Lohner, Valerie; Lorenzovici, László; Lotufo, Paulo A; Lucchetti, Giancarlo; Lusk, Jay B; Lutzky Saute, Ricardo; M Amin, Hawraz Ibrahim; Malhotra, Armaan K; Malhotra, Kashish; Malik, Ahmad Azam; Malta, Deborah Carvalho; Mansournia, Mohammad Ali; Mantovani, Lorenzo Giovanni; Manu, Emmanuel; Marateb, Hamid Reza; Marino, Mirko; Maroufi, Seyed Farzad; Martinez-Piedra, Ramon; Martini, Santi; Martorell, Miquel; Marzo, Roy Rillera; Mathangasinghe, Yasith; Mathews, Elezebeth; Maugeri, Andrea; McPhail, Steven M; Mehmood, Asim; Mehndiratta, Man Mohan; Mehrabani-Zeinabad, Kamran; Menezes, Ritesh G; Meo, Sultan Ayoub; Meretoja, Atte; Mestrovic, Tomislav; Mettananda, Chamila Dinushi Kukulege; Miazgowski, Tomasz; Micheletti Gomide Nogueira de Sá, Ana Carolina; Minervini, Giuseppe; Minh, Le Huu Nhat; Mirica, Andreea; Mirrakhimov, Erkin M; Mirza-Aghazadeh-Attari, Mohammad; Mishra, Ajay Kumar; Mithra, Prasanna; Mohamed, Abdalla Z; Mohamed, Ahmed Ismail; Mohammad, Ameen Mosa; Mohammadi, Soheil; Mohammadian-Hafshejani, Abdollah; Mohammed, Shafiu; Mokdad, Ali H; Molinaro, Sabrina; Momani, Shaher; Moni, Mohammad Ali; Moodi Ghalibaf, AmirAli; Moradi, Maryam; Moradi, Yousef; Moraga, Paula; Morawska, Lidia; Msherghi, Ahmed; Munjal, Kavita; Murray, Christopher JL; Nagarajan, Ahamarshan Jayaraman; Naik, Ganesh R; Najdaghi, Soroush; Nakhostin Ansari, Noureddin; Nargus, Shumaila; Davani, Delaram Narimani; Natto, Zuhair S; Nauman, Javaid; Nayak, Vinod C; Nazri-Panjaki, Athare; Negoi, Ruxandra Irina; Nematollahi, Soroush; Newton, Charles Richard James; Nguyen, Duc Hoang; Nguyen, Hau Thi Hien; Nguyen, Hien Quang; Nguyen, Phat Tuan; Nguyen, Van Thanh; Niazi, Robina Khan; Nigatu, Yeshambel T; Nikoobar, Ali; Nogueira de Sá, Antonio Tolentino; Nomura, Shuhei; Noubiap, Jean Jacques; Nugen, Fred; Nzoputam, Chimezie Igwegbe; Oancea, Bogdan; Oduro, Michael Safo; Ojo-Akosile, Tolulope R; Okati-Aliabad, Hassan; Okeke, Sylvester Reuben; Okekunle, Akinkunmi Paul; Olagunju, Andrew T; Olaiya, Muideen Tunbosun; Oliveira, Arão Belitardo; Oliveira, Gláucia Maria Moraes; Olorukooba, Abdulhakeem Abayomi; Olufadewa, Isaac Iyinoluwa; Ornello, Raffaele; Ortiz-Prado, Esteban; Osuagwu, Uchechukwu Levi; Ouyahia, Amel; Owolabi, Mayowa O; Ozair, Ahmad; P A, Mahesh Padukudru; Padron-Monedero, Alicia; Padubidri, Jagadish Rao; Panagiotakos, Demosthenes; Panos, Georgios D; Panos, Leonidas D; Pantazopoulos, Ioannis; Parikh, Romil R; Park, Seoyeon; Patel, Jay; Patel, Urvish K; Patoulias, Dimitrios; Pedersini, Paolo; Peprah, Emmanuel K; Pereira, Gavin; Perianayagam, Arokiasamy; Perico, Norberto; Perna, Simone; Petermann-Rocha, Fanny Emily; Philip, Anil K; Piradov, Michael A; Plotnikov, Evgenii; Polibin, Roman V; Postma, Maarten J; Pradhan, Jalandhar; Prasad, Manya; Puvvula, Jagadeesh; Qasim, Nameer Hashim; Qian, Gangzhen; Raggi, Alberto; Rahim, Fakher; Rahimi-Movaghar, Vafa; Rahman, Mosiur; Rahman, Muhammad Aziz; Rahmani, Amir Masoud; Rahmanian, Mohammad; Rajaa, Sathish; Rajabpour Sanati, Ali; Rajpoot, Pushp Lata; Rajput, Prashant; Ramadan, Mahmoud Mohammed; Ramasamy, Shakthi Kumaran; Ramazanu, Sheena; Rane, Amey; Rashedi, Sina; Rashidi, Mohammad-Mahdi; Rathish, Devarajan; Rawaf, Salman; Razo, Christian; Reddy, Murali Mohan Rama Krishna; Redwan, Elrashdy; Remuzzi, Giuseppe; Rezaei, Nazila; Rezaei, Negar; Rezaeian, Mohsen; Rocha, Hermano Alexandre Lima; Rodriguez, Jefferson Antonio Buendia; Roever, Leonardo; Romoli, Michele; Romozzi, Marina; Ross, Allen Guy; Rout, Himanshu Sekhar; Roy, Nitai; Roy, Priyanka; Saad, Aly MA; Saadatian, Zahra; Sabour, Siamak; Sacco, Simona; Saddik, Basema Ahmad; Sadeghi, Erfan; Saeed, Usman; Saheb Sharif-Askari, Fatemeh; Sahebkar, Amirhossein; Sahoo, Pragyan Monalisa; Sajib, Md Refat Uz Zaman; Salaroli, Luciane B; Saleh, Mohamed A; Samodra, Yoseph Leonardo; Samuel, Vijaya Paul; Samy, Abdallah M; Santric-Milicevic, Milena M; Saravanan, Aswini; Sarkar, Tanmay; Sarode, Gargi Sachin; Sarode, Sachin C; Sartorius, Benn; Satpathy, Maheswar; Schlaich, Markus P; Schneider, Ione Jayce Ceola; Schuermans, Art; Selvaraj, Siddharthan; Senthilkumaran, Subramanian; Sepanlou, Sadaf G; Sethi, Yashendra; Seylani, Allen; Shaaban, Ahmed Nabil; Shafie, Mahan; Shahwan, Moyad Jamal; Shaikh, Masood Ali; Shaikh, Summaiya Zareen; Shamim, Muhammad Aaqib; Shamsi, Anas; Shamsutdinova, Alfiya; Shanawaz, Mohd; Shannawaz, Mohammed; Sharifan, Amin; Sharifi Rad, Javad; Sharma, Vishal; Shashamo, Bereket Beyene; Shetty, Mahabalesh; Shetty, Premalatha K; Shigematsu, Mika; Shittu, Aminu; Shiue, Ivy; Shlobin, Nathan A; Shorofi, Seyed Afshin; Siddig, Emmanuel Edwar; Singh, Baljinder; Singh, Paramdeep; Singh, Puneetpal; Singh, Surjit; Sobia, Farrukh; Solanki, Ranjan; Solanki, Shipra; Soraneh, Soroush; Spartalis, Michael; Srinivasamurthy, Suresh Kumar; Stanaway, Jeffrey D; Stanikzai, Muhammad Haroon; Starodubova, Antonina V; Sun, Jing; Sun, Zhong; Swain, Chandan Kumar; Szarpak, Lukasz; Tabaee Damavandi, Payam; Tabatabaei, Seyyed Mohammad; Tabatabaeizadeh, Seyed-Amir; Tabche, Celine; Taiba, Jabeen; Talaat, Iman M; Tamuzi, Jacques Lukenze; Tan, Ker-Kan; Temsah, Mohamad-Hani; Teramoto, Masayuki; Thakur, Ramna; Thankappan, Kavumpurathu Raman; Thayakaran, Rasiah; Thirunavukkarasu, Sathish; Ticoalu, Jansje Henny Vera; Tiwari, Krishna; Tonelli, Marcello; Topor-Madry, Roman; Tovani-Palone, Marcos Roberto; Tran, An Thien; Tran, Jasmine T; Tran, Thang Huu; Tran Minh Duc, Nguyen; Truelsen, Thomas Clement; Truyen, Thien Tan Tri Tai; Tsai, Daniel Hsiang-Te; Ullah, Atta; Unim, Brigid; Unnikrishnan, Bhaskaran; Unsworth, Carolyn Anne; Usman, Jibrin Sammani; Vahdati, Sanaz; Vaithinathan, Asokan Govindaraj; Valizadeh, Rohollah; Van den Eynde, Jef; Varghese, Joe; Vasankari, Tommi Juhani; Venketasubramanian, Narayanaswamy; Vervoort, Dominique; Villafañe, Jorge Hugo; Vinayak, Manish; Vladimirov, Sergey Konstantinovitch; Wafa, Hatem A; Waheed, Yasir; Wahood, Waseem; Walde, Mandaras Tariku; Wang, Yanzhong; Wickramasinghe, Nuwan Darshana; Willeit, Peter; Wolde, Asrat Arja; Wolfe, Charles DA; Wubie, Yihun Miskir; Xiao, Hong; Xu, Suowen; Xu, Xiaoyue; Yamagishi, Kazumasa; Yano, Yuichiro; Yarahmadi, Amir; Yaribeygi, Habib; Yaya, Sanni; Ye, Pengpeng; Yon, Dong Keon; Yonemoto, Naohiro; Yu, Chuanhua; Zanghì, Aurora; Zare, Iman; Zastrozhin, Michael; Zhang, Chen; Zhang, Yunquan; Zhang, Zhi-Jiang; Zhang, Zhiqiang; Zhao, Hanqing; Zhou, Shang Cheng; Zhumagaliuly, Abzal; Zia, Hafsa; Zielinska, Magdalena; Zyoud, Samer H; Roth, Gregory A; Feigin, Valery LIMPORTANCE: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. OBJECTIVE: To estimate the worldwide burden of SAH. DESIGN, SETTING, AND PARTICIPANTS: Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. EXPOSURES: SAH and 14 modifiable risk factors. MAIN OUTCOMES AND MEASURES: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs). RESULTS: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. CONCLUSIONS AND RELEVANCE: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.Item Refining Stroke Prediction in Atrial Fibrillation Patients in an Ethnically Diverse Population: A Study Protocol(S. Karger AG, 2025) Mahawish, Karim M; Zeng, Irene; White, Harvey; Feigin, Valery; Krishnamurthi, RitaBACKGROUND: Atrial fibrillation (AF) increases ischaemic stroke (IS) risk, which can be mitigated using risk prediction models to guide anticoagulation decisions. This resultant widespread use of anticoagulants has reduced IS rates globally. However, commonly used risk prediction scores were validated in mainly European cohorts. Cardiology society guidelines recommend the local refinement of such risk scores to improve risk prediction. This study aims: 1. To determine trends in the prevalence of AF associated IS in Auckland. 2. To perform a validation study of the CHA2DS2 VASc risk score (Congestive heart failure, Hypertension, Age ≥ 75 [doubled], Diabetes, IS/TIA/thromboembolism [doubled] - Vascular disease (e.g. ischaemic heart disease, aortic plaque, etyc.), Age 65-74, and Sex [female]), and determine if additional ethnicity factors (i.e. Māori and Pacific peoples) improve risk prediction. 3. To identify associations with anticoagulant failure (i.e. IS on anticoagulation). METHODS: This study will utilise data from the Auckland Regional Community Stroke Study [ARCOS IV (2010-11) and V (2020-21) respectively], a comprehensive registry of stroke patients. The comparative controls will be Auckland residents diagnosed with AF between 1988-2020, sampled from the National Minimum Dataset (NMD)- a database of hospital discharge codes collated by Manatū Hauora (the New Zealand Ministry of Health). Firstly, we will investigate trends in the prevalence of AF associated IS and TIA in ARCOS IV and V. Secondly, we will use a nested case-control design by combining ARCOS V and NMD to determine the model performance of CHA2DS2 VASc and risk score refinements stratified by ethnicity. The effect of a. stroke aetiology, b. antithrombotic prescribing factors, and c. potential interactions will also be assessed in the data analysis. Based on sample size estimations, we will require a sample of 1493 controls and 374 cases with IS/TIA. CONCLUSION: Utilising data from three datasets will allow us to assess the burden and management of AF at a population level, identify trends in disease, address knowledge gaps in the management of ethnically diverse populations, and explore associations with treatment failure. Our reporting will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines.Item Long-term Mortality Outcome of a Primary Care-based Mobile Health Intervention for Stroke Management: Six-year Follow-up of a Cluster-randomized Controlled Trial(Public Library of Science (PLoS), 2025) Chen, Xingxing; Gong, Enying; Tan, Jie; Turner, Elizabeth L; Gallis, John A; Sun, Shifeng; Luo, Siran; Wu, Fei; Yang, Bolu; Long, Yutong; Wang, Yilong; Li, Zixiao; Zhou, Yun; Tang, Shenglan; Bettger, Janet P; Oldenburg, Brian; Zhang, Xiaochen; Gao, Jianfeng; Mittman, Brian S; Feigin, Valery L; Shao, Ruitai; Ebrahim, Shah; Yan, Lijing LBACKGROUND: Despite growing evidence of primary care-based interventions for chronic disease management in resource-limited settings, long-term post-trial effects remain inconclusive. We investigated the association of a 12-month system-integrated technology-enabled model of care (SINEMA) intervention with mortality outcomes among patients experiencing stroke at 6-year post-trial. METHODS AND FINDINGS: This study (clinicaltrial .gov registration number: NCT05792618) is a long-term passive observational follow-up of participants and their spouse of the SINEMA trial (clinicaltrial .gov registration number: NCT03185858). The original SINEMA trial was a cluster-randomized controlled trial conducted in 50 villages (clusters) in rural China among patients experiencing stroke during July 2017-July 2018. Village doctors in the intervention arm received training, incentives, and a customized mobile health application supporting monthly follow-ups to participants who also received daily free automated voice-messages. Vital status and causes of death were ascertained using local death registry, standardized village doctor records, and verbal autopsy. The post-trial observational follow-up spanned from 13- to 70-months post-baseline (up to April 30, 2023), during which no intervention was requested or supported. The primary outcome of this study was all-cause mortality, with cardiovascular and stroke cause-specific mortality also reported. Cox proportional hazards models with cluster-robust standard errors were used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs), adjusting for town, age, and sex in the main analysis model. Analyses were conducted on an intention-to-treat basis. Of 1,299 patients experiencing stroke (mean age 65.7 years, 42.6% females) followed-up to 6 years, 276 (21.2%) died (median time-to-death 43.0 months [quantile 1-quantile 3: 26.7-56.8]). Cumulative incidence of all-cause mortality was 19.0% (121 among 637) in the intervention arm versus 23.4% (155 among 662) in the control arm (HR 0.73; 95% CI 0.59, 0.90; p = 0.004); 14.4% versus 17.7% (HR 0.73; 95% CI 0.58, 0.94; p = 0.013) for cardiovascular cause-specific mortality; and 6.0% versus 7.9% (HR 0.71; 95% CI 0.44, 1.15; p = 0.16) for stroke cause-specific mortality. Although multisource verification was used to verify the outcomes, limitations exist as the survey- and record-matching-based nature of the study, unavailability of accurate clinical diagnostic records for some cases and the potential confounders that may influence the observed association on mortality. CONCLUSIONS: Despite no observed statistically difference on stroke cause-specific mortality, the 12-month SINEMA intervention, compared with usual care, significantly associated with reduced all-cause and cardiovascular cause-specific mortality during 6 years of follow-up, suggesting potential sustained long-term benefits to patients experiencing stroke.Item Multiple Long-Term Conditions, Co-Long-Term Conditions and Polyvascular Disease: Considerations for Evidence Synthesis and Meta-Analyses(Wiley, 2025) Mead, Gillian; Todhunter‐Brown, Alex; Abaraogu, Ukachukwu; Barugh, Amanda; Chauhan, Arohi; Lopez, Juan Erviti; Feigin, Valery; Kshatri, Jaya Singh; Mizuno, Atsushi; Pati, Sanghamitra; Price, Jackie; Providência, Rui; Stansby, Gerry; Taylor, Rod; Williams, David J; Wright, James M; Wu, Simiao; Flicker, LeonCochrane's scientific strategy for 2025 to 2030 has four research priorities, including improving the lives of people living with multiple chronic conditions. The purpose of this article written by the Cochrane Thematic Group in Heart, Stroke and Circulation is to explore considerations around multiple chronic conditions (also referred to as ‘multiple long‐term conditions’ i.e. two or more long‐term conditions) in systematic reviews. Rather than using the term ‘comorbidity’, we introduce a new term ‘co‐long‐term conditions’. We also explore how to define ‘polyvascular disease’. We suggest that review authors consider co‐long‐term conditions and multiple long‐term conditions in their reviews e.g. extract data about how primary studies address co‐long‐term conditions, perform subgroup analyses according to presence or not of co‐long‐term conditions, and include a section in the discussion about how well participants with co‐long‐term conditions were represented in the primary studies. This is especially pertinent for reviews addressing heart, circulatory or stroke disease, and polyvascular disease.Item Refining Predictive Risk Models for Stroke in Atrial Fibrillation: A Scoping Review and Meta-analysis for Aotearoa New Zealand, Māori and Pacific Peoples(Pasifika Medical Association Group, 2025) Mahawish, Karim M; White, Harvey; Feigin, Valery; Krishnamurthi, RitaAIM: The predictive risk model CHA2DS2 VASc helps clinicians assess the risk of stroke in patients with atrial fibrillation (AF). Originally developed and validated in predominantly European populations, it may not accurately reflect the stroke risk for diverse ethnic groups; in Aotearoa New Zealand, Māori and Pacific peoples with AF are at higher stroke risk. As part of global efforts to address health inequities, there is growing interest in adapting predictive models to suit local- and ethnic-specific risks better. Our objectives were to determine: 1) if stroke risk from AF varies by ethnic background/race, 2) stroke rates in non-anticoagulated AF cohorts, and 3) model performance of CHA2DS2 VASc across different geographical regions. Finally, we provide an overview of methodological considerations for risk model development. METHODS: We searched English language peer-reviewed studies reporting stroke rates in unselected cohorts with AF, published between 1995 and 2024. For stroke risk, we included cohorts with over 5,000 non-anticoagulated patients. The sources of evidence were PubMed, Scopus and EMBASE. RESULTS: Twenty-seven studies were eligible for inclusion. We found significantly elevated stroke risk in African Americans and Hispanics with AF compared with whites (odds ratio [OR] 1.44 [95% confidence interval (CI) 1.25-1.66] and OR 1.11 [95% CI 1.05-1.18] respectively). In Māori and Pacific peoples with AF, the risk of stroke was higher than in New Zealand Europeans, but this difference was not significant (OR 1.28 [95% CI 0.89-1.82], p=0.18 and OR 1.29 [95% CI 0.93-1.52], p=0.17 respectively). Stroke risk (0.6/100-6.8/100 person-years) and CHA2DS2 VASc performance (c-statistics 0.55-0.8) varied substantially between studies. CONCLUSION: We support the local refinement of risk prediction models in line with cardiology society recommendations.Item Trends in Stroke Incidence, Death, and Disability Outcomes in a Multi-Ethnic Population: Auckland Regional Community Stroke Studies (1981–2022)(Elsevier BV, 2025-03) Feigin, Valery L; Krishnamurthi, Rita; Nair, Balakrishnan; Rautalin, Ilari; Parag, Varsha; Anderson, Craig S; Arroll, Bruce; Barber, P Alan; Barker-Collo, Suzanne; Bennett, Derrick; Brown, Paul; Cadilhac, Dominque A; Douwes, Jeroen; Exeter, Daniel; Ranta, Anna; Ratnasabapathy, Yogini; Swain, Andrew; Tautolo, El-Shadan; Te Ao, Braden; Thrift, Amanda; Tunnage, BronwynBackground Reliable data on trends of stroke incidence and outcomes over time are necessary for assessing the effectiveness of public health and clinical strategies, and for allocating healthcare resources. We assessed the levels and trends in incidence, mortality, early case fatality and disability for stroke in a defined, ethnically mixed population over 40 years. Methods To analyse data from five population-based stroke incidence studies in adult residents (age ≥15 years) of the Greater Auckland Region of New Zealand (NZ) (1.35 million) over 12-month calendar periods for 1981–1982, 1991–1992, 2002–2003, 2011–2012, and 2021–2022. Fatal and non-fatal, hospitalised and non-hospitalised stroke events (first-ever and recurrent) were identified through multiple overlapping sources using clinical World Health Organization (WHO) diagnostic criteria and neuroimaging to define three major pathological types of stroke: ischaemic stroke (IS), primary intracerebral haemorrhage (PICH), subarachnoid haemorrhage (SAH), and stroke of undetermined type (SUT). Crude and age-standardised annual incidence, mortality, 28-day case fatality and disability level, and 40-year trends were calculated by age, sex, and ethnicity assuming a Poisson distribution. For comparison of our findings, we carried out a pooled analysis of methodologically comparable population-based stroke epidemiology estimates in high-income countries over the last two decades. Findings Overall, there were 7462 first-ever strokes (9917 events) over the 40-year period (4,682,012 person-years). From 1981–1982 to 2021–2022, age-standardised stroke incidence rates decreased from 156/100,000 (95% confidence interval [CI] 143; 170) to 124/100,000 (119; 130) and mortality rates from 98/100,000 (88; 110) to 28/100,000 (26; 31) in nearly all age, sex, and ethnic groups. Moreover, from 2002–2003 to 2021–2022, there was an increase in stroke incidence of 1.28% per year (95% CI 0.38–2.17) in people aged 15–54 years, with the mean age of people with stroke decreasing from 73.0 (SD ± 13.8) in 2002–2003 to 71.6 (SD ± 14.9) in 2011–2012 and 70.7 (SD ± 15.2) years in 2021–2022 (p for trend <0.0001). The risk of stroke in Māori and Pacific people in 2021–2022 was almost 1.5 and 2.0 times greater than that in NZ Europeans. Ethnic disparities in the risk of stroke and age of stroke onset remained stable over the study period. From 1981–1982 to 2021–2022, 28-day stroke case fatality declined from 33.1% to 12.1% (p < 0.0001). There was a trend towards reducing 28-day case-fatality (from 31.6% [95% CI 27.6; 35.7] in 1981–1982 to 11.4% [10.0; 12.7] in 2021–2022) and an increasing proportion of stroke survivors with good functional outcome at discharge/28-days post-stroke (increased from 45.7% (95% CI 41.3; 50.0) in 1981–1982 to 60.2% (58.1; 62.3) in 2021–2022). Interpretation Stroke incidence, 1-year mortality and 28-day case-fatality and disability have decreased in Auckland, NZ over the last 4 decades. However, over the last decade (2011–2022) there was a stagnation in the decline in the age-standardised stroke incidence rates. The absolute numbers of people with strokes, and those who have died or remained disabled from stroke, have significantly increased from 1981 to 2022. Ethnic disparities in the risk and burden of stroke persist. Effective prevention strategies for stroke must remain a high priority.Item Characterizing Positive and Negative Quantitative Susceptibility Values in the Cortex Following Mild Traumatic Brain Injury: A Depth- and Curvature-Based Study(Oxford University Press, 2025-03-18) Essex, Christi A; Merenstein, Jenna L; Overson, Devon K; Truong, Trong-Kha; Madden, David J; Bedggood, Mayan; Murray, Helen; Holdsworth, Samantha J; Stewart, Ashley W; Morgan, Catherine; Faull, Richard LM; Hume, Patria; Theadom, Alice; Pedersen, MangorEvidence has linked head trauma to increased risk factors for neuropathology, including mechanical deformation of the sulcal fundus and, later, perivascular accumulation of hyperphosphorylated tau adjacent to these spaces related to chronic traumatic encephalopathy. However, little is known about microstructural abnormalities and cellular dyshomeostasis in acute mild traumatic brain injury in humans, particularly in the cortex. To address this gap, we designed the first architectonically motivated quantitative susceptibility mapping study to assess regional patterns of net positive (iron-related) and net negative (myelin-, calcium-, and protein-related) magnetic susceptibility across 34 cortical regions of interest following mild traumatic brain injury. Bilateral, between-group analyses sensitive to cortical depth and curvature were conducted between 25 males with acute (<14 d) sports-related mild traumatic brain injury and 25 age-matched male controls. Results suggest a trauma-induced increase in net positive susceptibility focal to superficial, perivascular-adjacent spaces in the parahippocampal sulcus. Decreases in net negative susceptibility values in distinct voxel populations within the same region indicate a potential dual pathology of neural substrates. These mild traumatic brain injury-related patterns were distinct from age-related processes revealed by correlation analyses. Our findings suggest depth- and curvature-specific deposition of biological substrates in cortical tissue convergent with features of misfolded proteins in trauma-related neurodegeneration.Item Applying Generalizability Theory to Examine Assessments of Subjective Cognitive Complaints: Whose Reports Should We Rely on – Participant Versus Informant?(Cambridge University Press (CUP), 2021) Medvedev, ON; Feigin, VL; Sachdev, PS; Kochan, NA; Brodaty, H; Merkin, AG; Numbers, K; Choo, C; Truong, QCObjectives: This study aimed to apply the generalizability theory (G-theory) to investigate dynamic and enduring patterns of subjective cognitive complaints (SCC), and reliability of two widely used SCC assessment tools. Design: G-theory was applied to assessment scales using longitudinal measurement design with five assessments spanning 10 years of follow-up. Setting: Community-dwelling older adults aged 70–90 years and their informants, living in Sydney, Australia, participated in the longitudinal Sydney Memory and Ageing Study. Participants: The sample included 232 participants aged 70 years and older, and 232 associated informants. Participants were predominantly White Europeans (97.8%). The sample of informants included 76 males (32.8%), 153 females (65.9%), and their age ranged from 27 to 86 years, with a mean age of 61.3 years (SD = 14.38). Measurements: The Memory Complaint Questionnaire (MAC-Q) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Results: The IQCODE demonstrated strong reliability in measuring enduring patterns of SCC with G = 0.86. Marginally acceptable reliability of the 6-item MAC-Q (G = 0.77–0.80) was optimized by removing one item resulting in G = 0.80–0.81. Most items of both assessments were measuring enduring SCC with exception of one dynamic MAC-Q item. The IQCODE significantly predicted global cognition scores and risk of dementia incident across all occasions, while MAC-Q scores were only significant predictors on some occasions. Conclusions: While both informants’ (IQCODE) and self-reported (MAC-Q) SCC scores were generalizable across sample population and occasions, self-reported (MAC-Q) scores may be less accurate in predicting cognitive ability and diagnosis of each individual.Item ASHA Workers During COVID-19 in India: At the Intersection of Gender and Work(SAGE Publications, 2025) Menon, Shaveta; Bisht, Ramila; Nair, BalakrishnanIndia requires expanded efforts for reaching the healthcare needs of its vulnerable community. Due to a shortage of qualified health workforce, particularly in rural India, less-skilled health workers are selected and trained to mobilise these efforts. These community health workers (CHWs) are primarily women who work as an interface between the communities and the health system. These workers face several systemic challenges like high workloads, insufficient training and little or no feedback about performance. But apart from these, the CHWs also face several challenges that adversely impact their individual and family health and well-being, disrupting their work–life balance. Performing multiple roles results in strain in the balance, affecting their job and quality of life. The imbalance was noticeable in CHWs playing a pivotal role in fighting the recent pandemic in a less resilient health system. We explore these experiences of imbalance across the Indian sub-continent based on published literature and broadcasted stories from social networking platforms, investigate these work and family stressors and outline the reasons for their occurrence among female CHWs. Some stories revealed inequitable access to COVID-19 prevention kits, gender disparities, unpaid wages and lack of psychosocial support for their mental well-being. At the same time, they negotiate through the structural nuances of the Indian health system. This triple burden of dealing with employment, family and structures during these COVID times has amplified their daily struggles as CHWs and women. The article hypothesises that a balanced work–life interface for CHWs matters for improved organisational performance, gender equality and a better quality of life for their children. We performed a systematic review of CHW-related literature and a thematic analysis of stories from social media and print media from March 2020 to March 2021. The research findings attempt to inform the organisation policies responsible for ensuring that their employees are treated fairly and provided with their employment rights. The Indian public health system that supports these CHWs need to engage in ethical work practices that are legal, fair and ensure decent treatment of the workforce by providing conditions that do not harm the staff.Item Global, Regional, and National Burden of Epilepsy, 1990–2021: A Systematic Analysis for the Global Burden of Disease Study 2021(Elsevier BV, 2025) Feigin, Valery L; Vos, Theo; Nair, Balakrishnan Sukumaran; Hay, Simon I; Abate, Yohannes Habtegiorgis; Abd Al Magied, Abdallah HA; Abd ElHafeez, Samar; Abdelkader, Atef; Abdollahifar, Mohammad-Amin; Abdullahi, Auwal; Aboagye, Richard Gyan; Abreu, Lucas Guimarães; Abu Rumeileh, Samir; Abualruz, Hasan; Aburuz, Salahdein; Abu-Zaid, Ahmed; Addo, Isaac Yeboah; Adedoyin, Rufus Adesoji; Adepoju, Abiola Victor; Afzal, Muhammad Sohail; Afzal, Saira; Ahmad, Aqeel; Ahmad, Sajjad; Ahmad, Tauseef; Ahmadi, Ali; Ahmadzade, Amir Mahmoud; Ahmed, Ayman; Ahmed, Haroon; Ahmed, Mehrunnisha Sharif; Ahmed, Muktar Beshir; Al Awaidy, Salah; Al Omari, Omar; Al-Ajlouni, Yazan; Albashtawy, Mohammed; Al-Fatly, Bassam; Algammal, Abdelazeem M; Ali, Abid; Ali, Mohammed Usman; Ali, Syed Shujait; Ali, Waad; Alif, Sheikh Mohammad; Almazan, Joseph Uy; Alshahrani, Najim Z; Altaf, Awais; Al-Wardat, Mohammad; Al-Worafi, Yaser Mohammed; Aly, Hany; Alzoubi, Karem H; Amiri, Sohrab; Ancuceanu, Robert; Angappan, Dhanalakshmi; Ansari, Mohammed Tahir; Anvari, Saeid; Anyasodor, Anayochukwu Edward; Arabloo, Jalal; Arafat, Mosab; Aravkin, Aleksandr Y; Aregawi, Brhane Berhe; Aremu, Abdulfatai; Atout, Maha Moh'd Wahbi; Atreya, Alok; Aujayeb, Avinash; Aychiluhm, Setognal Birara; Aziz, Shahkaar; Azzam, Ahmed Y; Badiye, Ashish D; Bai, Ruhai; Baig, Atif Amin; Bakkannavar, Shankar M; Bandyopadhyay, Soham; Banerjee, Indrajit; Bardhan, Mainak; Barker-Collo, Suzanne Lyn; Barrow, Amadou; Basharat, Zarrin; Bashiri, Azadeh; Basiru, Afisu; Bastan, Mohammad-Mahdi; Batchu, Sai; Behnam, Babak; Bejarano Ramirez, Diana Fernanda; Bemanalizadeh, Maryam; Beyene, Kebede A; Bhagat, Devidas S; Bhagavathula, Akshaya Srikanth; Bhaskar, Sonu; Bhat, Ajay Nagesh; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh; Bhuiyan, Mohiuddin Ahmed; Bhuyan, Soumitra S; Bilgin, Cem; Bisulli, Francesca; Boloor, Archith; Boppana, Sri Harsha; Bouaoud, Souad; Bustanji, Yasser; Çakmak Barsbay, Mehtap; Carvalho, Felix; Castaldelli-Maia, Joao Mauricio; Chandika, Rama Mohan; Chattu, Vijay Kumar; Chaudhary, Anis Ahmad; Ching, Patrick R; Chopra, Hitesh; Chu, Dinh-Toi; Chu, Hongyuan; Cortese, Samuele; Cortesi, Paolo Angelo; Cruz-Martins, Natalia; Dadras, Omid; Dai, Xiaochen; D'Amico, Emanuele; Dandona, Lalit; Dandona, Rakhi; Darcho, Samuel Demissie; Darwish, Amira Hamed; Dhane, Amol S; Dhulipala, Vishal R; Diaz, Michael J; Do, Thanh Chi; Dohare, Sushil; Doshi, Ojas Prakashbhai; Dsouza, Haneil Larson; Dziedzic, Arkadiusz Marian; Ebrahimi, Alireza; Eissazade, Negin; Ekholuenetale, Michael; El Arab, Rabie Adel; El Bayoumy, Ibrahim Farahat; El Meligy, Omar Abdelsadek Abdou; Elhabashy, Hala Rashad; Elhadi, Muhammed; Eltaha, Chadi; Fagbamigbe, Adeniyi Francis; Fahim, Ayesha; Fares, Jawad; Farjoud Kouhanjani, Mohsen; Fasanmi, Abidemi Omolara; Fatehizadeh, Ali; Fazeli, Patrick; Fazylov, Timur; Fekadu, Ginenus; Fereshtehnejad, Seyed-Mohammad; Ferrara, Pietro; Ferreira, Nuno; Fetensa, Getahun; Fischer, Florian; Foschi, Matteo; Gadanya, Muktar A; Galali, Yaseen; Ganesan, Balasankar; Gao, Xiang; Garg, Ravindra Kumar; Gebregergis, Miglas Welay; Ghadirian, Fataneh; Ghamari, Seyyed-Hadi; Gilani, Jaleed Ahmed; Girmay, Alem Abera; Giussani, Giorgia; Gnedovskaya, Elena V; Golechha, Mahaveer; Gouravani, Mahdi; Grada, Ayman; Guan, Shi-Yang; Gupta, Sapna; Haghani Dogahe, Mohammad; Haj-Mirzaian, Arvin; Hamdy, Nadia M; Harlianto, Netanja I; Hasaballah, Ahmed I; Hasani, Hamidreza; Hassan, Amr; Hassan, Ikrama Ibrahim; Hassan Zadeh Tabatabaei, Mahgol Sadat; Hegazi, Omar E; Heidari, Golnaz; Hemmati, Mehdi; Hezam, Kamal; Hoan, Nguyen Quoc; Holla, Ramesh; Hosseinzadeh, Mehdi; Huang, Junjie; Huynh, Hong-Han; Hwang, Bing-Fang; Ibitoye, Segun Emmanuel; Ikiroma, Adalia; Ilesanmi, Olayinka Stephen; Ilic, Irena M; Ilic, Milena D; Imam, Mohammad Tarique; Immurana, Mustapha; Inok, Arit; Islam, Md Rabiul; Iwu, Chidozie Declan; Jacob, Louis; Jafarzadeh, Abdollah; Jahrami, Haitham; Jairoun, Ammar Abdulrahman; Jakovljevic, Mihajlo; Jalilzadeh Yengejeh, Reza; Jamora, Roland Dominic G; Jawaid, Talha; Jayapal, Sathish Kumar; Ji, Zixiang; Jonas, Jost B; Joseph, Nitin; Joshua, Charity Ehimwenma; Kabir, Zubair; Kalani, Rizwan; Kamireddy, Arun; Kanmodi, Kehinde Kazeem; Kapoor, Neeti; Kashoo, Faizan Zaffar; Kaur, Harkiran; Kazemi, Foad; Khajuria, Himanshu; Khalilian, Alireza; Khan, Maseer; Khatatbeh, Haitham; Khayat Kashani, Hamid Reza; Kheirallah, Khalid A; Khidri, Feriha Fatima; Khormali, Moein; Khosla, Atulya Aman; Khubchandani, Jagdish; Kim, Yun Jin; Kim, Yun Seo; Kimokoti, Ruth W; Koh, Hyun Yong; Kolahi, Ali-Asghar; Kostev, Karel; Krishan, Kewal; Krishnamoorthy, Vijay; Kruja, Jera; Kuddus, Mohammed; Kulimbet, Mukhtar; Kumar, G Anil; Kumar, Manasi; Kundu, Satyajit; Kytö, Ville; Lahariya, Chandrakant; Lal, Dharmesh Kumar; Lám, Judit; Landires, Iván; Lanfranchi, Francesco; Le, Nhi Huu Hanh; Lee, Seung Won; Ligade, Virendra S; Lim, Stephen S; Linehan, Christine; Liu, Xiaofeng; Liu, Xuefeng; López-Gil, José Francisco; Lucchetti, Giancarlo; Majeed, Azeem; Malhotra, Kashish; Malik, Ahmad Azam; Mansouri, Vahid; Marateb, Hamid Reza; Martorell, Miquel; Marzo, Roy Rillera; Mathangasinghe, Yasith; Mediratta, Rishi P; Mehndiratta, Man Mohan; Meles, Hadush Negash; Melese, Endalkachew Belayneh; Mensah, George A; Meretoja, Atte; Mestrovic, Tomislav; Mettananda, Sachith; Minervini, Giuseppe; Mirfakhraie, Reza; Mirza, Moonis; Misganaw, Awoke; Misra, Arup Kumar; Mohamed, Abdalla Z; Mohamed, Nouh Saad; Mohammadian-Hafshejani, Abdollah; Mohammadzadeh, Ibrahim; Mohan, Syam; Mokdad, Ali H; Monasta, Lorenzo; Moodi Ghalibaf, AmirAli; Moradi, Maryam; Motappa, Rohith; Muccioli, Lorenzo; Mulita, Francesk; Munkhsaikhan, Yanjinlkham; Murillo-Zamora, Efren; Muthu, Sathish; Nabavi, Amin; Naik, Ganesh R; Nargus, Shumaila; Nashwan, Abdulqadir J; Natto, Zuhair S; Nauman, Javaid; Naveed, Muhammad; Nayak, Biswa Prakash; Nazri-Panjaki, Athare; Nepal, Gaurav; Netsere, Henok Biresaw; Nguyen, Hau Thi Hien; Niazi, Robina Khan; Nikoobar, Ali; Nozari, Majid; Nri-Ezedi, Chisom Adaobi; Nwatah, Vincent Ebuka; Nzoputam, Ogochukwu Janet; Oancea, Bogdan; Olagunju, Andrew T; Olalusi, Oladotun Victor; Omar Bali, Ahmed; Ordak, Michal; Orish, Verner N; Ortiz-Prado, Esteban; Otstavnov, Nikita; Ouyahia, Amel; Owolabi, Mayowa O; Padron-Monedero, Alicia; Padubidri, Jagadish Rao; Panda, Sujogya Kumar; Panda-Jonas, Songhomitra; Pande Katare, Deepshikha; Pandey, Anamika; Panos, Leonidas D; Pantazopoulos, Ioannis; Papadopoulou, Paraskevi; Parekh, Utsav; Parikh, Romil R; Parsons, Nicholas; Passera, Roberto; Patil, Shankargouda; Pawar, Shrikant; Pazoki Toroudi, Hamidreza; Pensato, Umberto; Peprah, Prince; Peres, Mario FP; Perna, Simone; Pham, Hoang Nhat; Piracha, Zahra Zahid; Piradov, Michael A; Poddighe, Dimitri; Poluru, Ramesh; Pour-Rashidi, Ahmad; Pradhan, Jalandhar; Prasad, Manya; Pribadi, Dimas Ria Angga; Puvvula, Jagadeesh; Qasim, Nameer Hashim; Radhakrishnan, Venkatraman; Raghav, Pankaja; Rahim, Fakher; Rahman, Mosiur; Rahmani, Amir Masoud; Rahmanian, Mohammad; Raja, Adarsh; Rajabpour Sanati, Ali; Rajpoot, Pushp Lata; Ramadan, Mahmoud Mohammed; Ramasamy, Shakthi Kumaran; Rancic, Nemanja; Rao, Sowmya J; Rashidi, Mohammad-Mahdi; Rathish, Devarajan; Rawaf, Salman; Reddy, Murali Mohan Rama Krishna; Redwan, Elrashdy M Moustafa Mohamed; Rezaeian, Mohsen; Rhee, Taeho Gregory; Riaz, Muhammad; Rodriguez, Jefferson Antonio Buendia; Roever, Leonardo; Romozzi, Marina; Rony, Moustaq Karim Khan; Root, Kevin T; Rout, Himanshu Sekhar; Saad, Aly MA; Sabet, Cameron John; Saddik, Basema Ahmad; Sadeghian, Reihaneh; Saeb, Mohammad Reza; Saeed, Umar; Saeed, Usman; Saheb Sharif-Askari, Fatemeh; Saheb Sharif-Askari, Narjes; Sahebkar, Amirhossein; Saif, Zahra; Sajadi, S Mohammad; Salami, Afeez Abolarinwa; Salimi, Sohrab; Samodra, Yoseph Leonardo; Samy, Abdallah M; Sarode, Gargi Sachin; Sarode, Sachin C; Sathian, Brijesh; Sathyanarayan, Anudeep; Satpathy, Maheswar; Sawhney, Monika; Selvaraj, Siddharthan; Semreen, Mohammad H; Sendekie, Ashenafi Kibret; Senthilkumaran, Subramanian; Sethi, Yashendra; Seylani, Allen; Shahbandi, Ataollah; Shahid, Samiah; Shaikh, Masood Ali; Shaikh, Summaiya Zareen; Shamim, Muhammad Aaqib; Shams-Beyranvand, Mehran; Shamsutdinova, Alfiya; Sharifan, Amin; Sharifi Rad, Javad; Sharma, Anupam; Sharma, Vishal; Shayan, Maryam; Sheikh, Zubeda Begum; Shetty, Mahabalesh; Shetty, Pavanchand H; Shetty, Premalatha K; Shittu, Aminu; Shlobin, Nathan A; Shorofi, Seyed Afshin; Shrestha, Sunil; Siddig, Emmanuel Edwar; Singh, Gagandeep; Singh, Harmanjit; Singh, Jasvinder A; Singh, Paramdeep; Singh, Puneetpal; Singh, Surjit; Solanki, Shipra; Soraneh, Soroush; Stanikzai, Muhammad Haroon; Sullman, Mark JM; Sunnerhagen, Katharina S; Suresh, Vinay; Swain, Chandan Kumar; Szarpak, Lukasz; Tabaee Damavandi, Payam; Tabarés-Seisdedos, Rafael; Tabche, Celine; Taiba, Jabeen; Tanwar, Manoj; Tareke, Minale; Temsah, Mohamad-Hani; Temsah, Reem Mohamad Hani; Teramoto, Masayuki; Thangaraju, Pugazhenthan; Thirunavukkarasu, Sathish; Ticoalu, Jansje Henny Vera; Tiruye, Tenaw Yimer; Tiwari, Krishna; Tiwari, Vikas Kumar; Tovani-Palone, Marcos Roberto; Tran, Thang Huu; Tran Minh Duc, Nguyen; Tripathi, Manjari; Tromans, Samuel Joseph; Tsai, Daniel Hsiang-Te; Tsatsakis, Aristidis; Tsermpini, Evangelia Eirini; Tumurkhuu, Munkhtuya; Udoakang, Aniefiok John; Ullah, Saeed; Umair, Muhammad; Unnikrishnan, Bhaskaran; Urso, Daniele; Usman, Jibrin Sammani; Vaithinathan, Asokan Govindaraj; Vakilian, Alireza; Varma, Ravi Prasad; Venketasubramanian, Narayanaswamy; Villafañe, Jorge Hugo; Vinayak, Manish; Vinueza Veloz, Andres Fernando; Walde, Mandaras Tariku; Wang, Shu; Wang, Yanzhong; Waris, Abdul; Wickramasinghe, Nuwan Darshana; Winkler, Andrea Sylvia; Yesuf, Subah Abderehim; Yiğit, Arzu; Yiğit, Vahit; Yilma, Mekdes Tigistu; Yismaw, Yazachew Engida; Yon, Dong Keon; Yonemoto, Naohiro; Yu, Chuanhua; Zandi, Milad; Zanghì, Aurora; Zeariya, Mohammed GM; Zhao, Zhongyi; Zhong, Claire Chenwen; Zielińska, Magdalena; Zitoun, Osama A; Zyoud, Sa'ed H; Zyoud, Samer H; Rautalin, Ilari; Newton, Charles Richard James; Wiebe, Samuel; Murray, Christopher JLBackground: Epilepsy is one of the most common serious neurological disorders and affects individuals of all ages across the globe. The aim of this study is to provide estimates of the epilepsy burden on the global, regional, and national levels for 1990–2021. Methods: Using well established Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) methodology, we quantified the prevalence of active idiopathic (epilepsy of genetic or unknown origin) and secondary epilepsy (epilepsy due to an underlying abnormality of the brain structure or chemistry), as well as incidence, death, and disability-adjusted life-years (DALYs) by age, sex, and location (globally, 21 GBD regions and seven super-regions, World Bank country income levels, Socio-demographic Index [SDI], and 204 countries) and their trends from 1990 to 2021. Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy, largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). Findings: In 2021, there were 51·7 million (95% UI 44·9–58·9) people with epilepsy (idiopathic and secondary combined) globally, with an age-standardised prevalence of 658 per 100 000 (569–748). Idiopathic epilepsy had an age-standardised prevalence of 307 per 100 000 (235–389) globally, with 24·2 million (18·5–30·7) prevalent cases, and secondary epilepsy had a global age-standardised prevalence of 350 per 100 000 (322–380). In 2021, 0·7% of the population had active epilepsy (0·3% attributed to idiopathic epilepsy and 0·4% to secondary epilepsy), and the age-standardised global prevalence of epilepsy from idiopathic and secondary epilepsy combined increased from 1990 to 2021 by 10·8% (1·1–21·3), mainly due to corresponding changes in secondary epilepsy. However, age-standardised death and DALY rates of idiopathic epilepsy reduced from 1990 to 2021 (decline of 15·8% [8·8–22·8] and 14·5% [4·2–24·2], respectively). There were three-fold to four-fold geographical differences in the burden of active idiopathic epilepsy, with the bulk of the burden residing in low-income to middle-income countries: 82·1% (81·1–83·4) of incident, 80·4% prevalent (79·7–82·7), 84·7% (83·7–85·1) fatal epilepsy, and 87·9% (86·2–89·2) epilepsy DALYs. Interpretation: Although the global trends in idiopathic epilepsy deaths and DALY rates have improved in the preceding decades, in 2021 there were almost 52 million people with active epilepsy (24 million from idiopathic epilepsy and 28 million from secondary epilepsy), with the bulk of the burden (>80%) residing in low-income to middle-income countries. Better treatment and prevention of epilepsy are required, along with further research on risk factors of idiopathic epilepsy, good-quality long-term epilepsy surveillance studies, and exploration of the possible effect of stigma and cultural differences in seeking medical attention for epilepsy.