Browsing by Author "Pandian, J.D."

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B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.
(Lancet Pub. Group, 2010) Hankey, G.J.; Eikelboom, J.W.; Baker, R.I.; Gelavis, A.; Hickling, S.C.; Jamrozik, K.; van Bockxmeer, F.M.; Vasikaran, S.; Chen, C.; Eikelboom, J.W.; Lees, K.R.; Yi, Q.; Hankey, G.J.; Algra, A.; Chen, C.; Wong, M.C.; Cheung, R.; Wong, I.; Divjak, I.; Ferro, J.; De Freitas, G.; Gommans, J.; Groppa, S.; Hill, M.; Spence, J.D.; Lees, K.R.; Lisheng, L.; Navarro, J.; Ranawaka, U.; Ricci, S.; Schmidt, R.; Slivka, A.; Tan, A.; Tsiskaridze, A.; Uddin, W.; Vanhooren, G.; Xavier, D.; Armitage, J.; Hobbs, M.; Le, M.; Sudlow, C.; Wheatley, K.; Yi, Q.; Brown, W.; Bulder, M.; Eikelboom, J.W.; Hankey, G.J.; Ho, W.K.; Jamrozik, K.; Klijn, C.J.; Koedam, E.; Langton, P.; Nijboer, E.; Tuch, P.; Pizzi, J.; Tang, M.; Alaparthi, R.; Antenucci, M.; Chew, Y.; Chinnery, C.; Cockayne, C.; Holt, R.; Loh, K.; McMullin, L.; Mulholland, G.; Nahoo, B.; Read, E.; Smith, F.; Yip, C.Y.; Hankey, G.J.; Loh, K.; Crimmins, D.; Davis, T.; England, M.; Rakic, V.; Schultz, D.W.; Frayne, J.; Bladin, C.; Kokkinos, J.; Dunbabin, D.; Harper, J.; Rees, P.; Warden, D.; Levi, C.; Parsons, M.; Russell, M.; Spratt, N.; Clayton, P.; Nayagam, P.; Sharp, J.; Grainger, K.; De Wytt, C.; McDougall, A.; Donnan, G.A.; Grimley, R.; Neynens, E.; Reinhart, B.; Ropele, S.; Schmidt, R.; Stögerer, E.; Dedeken, P.; Schelstraete, C.; Vanhooren, G.; Veyt, A.; Andre, C.; De Freitas, G.R.; Gomes, S.E.; Mok, V.C.; Wong, A.; Wong, L.K.; Cheung, R.T.; Li, L.S.; Pais, P.; Xavier, D.; Joshi, S.; Parthasaradhi, S.; Roy, A.K.; Varghese, R.V.; Kochar, K.; Panwar, R.B.; Chidambaram, N.; Rajasekaharan, U.; Bala, S.; Pandian, J.D.; Singh, Y.; Karadan, U.; Salam, A.; Shivkumar, S.; Sundararajan, A.; Joshi, R.; Kalantri, S.P.; Singh, H.; Rath, A.; Balasubramanian, N.T.; Kalanidhi, A.; Babu, K.; Bharani, A.; Choudhary, P.; Jain, M.; Agarwal, A.; Singh, M.; Agarwal, R.R.; Gupta, R.; Kothari, S.; Mijar, S.; Wadia, R.S.; Paul, S.K.; Sekhar Nandi, S.; Mehndiratta, M.M.; Tukaram, U.; Mittal, K.; Rohatgi, A.; Kumar, S.; Vinayan, K.P.; Muralidharan, R.S.; Celani, M.G.; Favorito, I.; Mazzoli, T.; Ricci, S.; Righetti, E.; Blundo, M.; Carnemolla, A.; D'Asta, A.; Giordano, A.; Iemolo, F.; Favorito, L.; Mazzoli, T.; Ricci, S.; Righetti, E.; Gresele, P.; Guercini, F.; Caporalini, R.; De Dominicis, L.; Giovagnetti, M.; Giuliani, G.; Paoletti, S.; Pucci, E.; Cavallini, A.; Persico, A.; Casoni, F.; Costa, A.; Magoni, M.; Spezi, R.; Tortorella, R.; Venturelli, E.; Vergani, V.; Caprioli, S.; Provisione, M.; Zanotta, D.; Abdullah, J.M.; Damitri, T.; Idris, B.; Sayuthi, S.; Hong, J.J.; Tan, C.T.; Tan, K.S.; Dutca, G.; Grigor, V.; Groppa, S.; Manea, D.; Achterberg, S.; Algra, A.; Halkes, P.H.; Kappelle, L.J.; Boon, A.M.; Doelman, J.C.; Sips, R.; Visscher, F.; Kwa, V.I.; Ternede, O.A.; van der Sande, J.J.; Frendin, T.; Gommans, J.; Anderson, N.E.; Bennett, P.; Charleston, A.; Spriggs, D.; Singh, J.; Bourke, J.; Bucknell, R.; McNaughton, H.; Anwar, A.; Murtaza, H.; Uddin, W.; Ismail, J.; Khan, N.U.; Navarro, J.C.; Amor, V.G.; Canete, M.T.; Lim, C.; Ravelo, E.B.; Siguenza, M.; Villahermosa, M.O.; Siguenza, M.; Canete, M.T.; Cardino, M.J.; Cenabre, R.; Gara, M.; Salas, Z.; Batac, A.; Canete, M.T.; Conde, L.; Dumdum, P.; Garcia, F.S.; Libarnes, S.; Matig-a, N.; Olanda, N.; Arcenas, R.; Canete, M.T.; Loraña, A.; Surdilla, A.; Araullo, M.L.; Lokin, J.; Maylem, G.; Marques, E.; Veloso, M.; Correia, M.; Lopes, G.; Canhão, P.; Ferro, J.M.; Melo, T.P.; Dias, A.; Sousa, A.P.; Tsiskaridze, A.; Vashadze, T.; Divjak, I.; Papic, V.; Chang, H.M.; Chen, C.P.; de Silva, D.A.; Tan, E.K.; Ranawaka, U.K.; Wijesekera, J.C.; de Silva, H.A.; Wijekoon, C.N.; Dawson, U.K.; Higgins, P.; Lees, K.R.; MacDonald, L.; McArthur, K.; McIlvenna, Y.; Quinn, T.; Walters, M.; Curless, R.; Dickson, J.; Murdy, J.; Scott, A.; Cameron, S.; Darnley, K.; Dennis, M.; Lyle, D.; Hunter, A.; Watt, M.; Watt, M.; Wiggam, I.; Murdy, J.; Rodgers, H.; Dick, F.; Macleod, M.; McKenzie, A.; Jones, P.; Jones, S.; Hussain, M.; Albazzaz, M.K.; Elliott, K.; Hardware, B.; Bacabac, E.; Martin, H.; Sharma, A.; Sutton, V.; Baht, H.; Cowie, L.; Gunathilagan, G.; Hargrove, D.R.; Smithard, D.J.; Adrian, M.; Bath, P.; Hammonds, F.; Maguire, H.; Roff, C.; Datta-chaudhuri, M.; Diyazee, K.; Krishnamoorthy, S.; McNulty, K.; Okwera, J.; Hilaire, C.; Kelly, D.; Barron, L.; James, M.; Wedge, N.; Bruce, M.; Macleod, M.; Barber, M.; Esson, D.; Ames, D.; Chataway, J.; Bulley, S.; Jenkins, K.; Rashed, K.; Dafalla, B.E.; Venugopalan, T.C.; Ball, M.; Punnoose, S.; Justin, F.; Sekaran, L.; Sethuraman, S.; Goddard, H.; Howard, J.; McIlmoyle, J.; Diver-Hall, C.; McCarron, M.; McNicholl, M.P.; Clamp, B.; Hunter, J.; Oke, A.; Weaver, A.; Fraser, P.; McAlpine, C.; Chambers, J.; Dymond, H.; Saunders, G.; Langhorne, P.; Stott, D.; Wright, F.; Adie, K.; Bland, R.; Courtauld, G.; Harrington, F.; James, A.; Mate, A.; Schofield, C.; Wroath, C.; Duberley, S.; Punekar, S.; Niranjan, K.; Sandler, D.; Krishna, P.; Moussouttas, M.; Notestine, M.A.; Slivka, A.; Vallini, D.; Hwang, T.; Saverance, M.; Booth, K.; Murphy, D.
BACKGROUND: Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. METHODS: In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444. FINDINGS: Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups. INTERPRETATION: Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins. FUNDING: Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia.
The burden, risk factors and unique etiologies of stroke in South-East Asia Region (SEAR)
(Elsevier, 2023) Pandian, J.D.; Srivastava, M.V.P.; Aaron, S.; Ranawaka, U.K.; Venketasubramanian, N.; Sebastian, I.A.; Injety, R.J.; Gandhi, D.B.C.; Chawla, N.S.; Vijayanand, P.J.; Rangamani, S.; Kalkonde, Y.V.
The World Health Organization (WHO) South East Asia Region (SEAR) comprises 11 countries, which are one of the most culturally, topographically, and socially diverse areas worldwide, undergoing an epidemiological transition towards non-communicable diseases, including stroke and other cardiovascular diseases (CVDs). This region accounts for over 40% of the global stroke mortality. Few well-designed population-based epidemiological studies on stroke are available from SEAR countries, with considerable variations among them. Ischemic stroke, a common stroke subtype, has higher frequencies of intracerebral hemorrhage in many countries. Along with an aging population, the increased prevalence of risk factors such as hypertension, diabetes mellitus, tobacco and alcohol consumption, lack of physical activity, high ambient pollution, heat, and humidity contribute to the high burden of stroke in this region. SEAR's many unique and uncommon stroke etiologies include cerebral venous thrombosis, tuberculosis, dengue, scrub typhus, falciparum malaria, snake bite, scorpion sting, etc. Current data on stroke burden and risk factors is lacking, compelling an urgent need for high-quality hospital-level and population-level data in all SEAR countries. Strategies towards a consolidated approach for implementing improved stroke prevention measures, stroke surveillance, and established stroke systems of care are the path to bridging the gaps in stroke care.
Cluster-randomized, crossover trial of head positioning in acute stroke
(Massachusetts Medical Society, 2017) Anderson, C.S.; Arima, H.; Lavados, P.; Billot, L.; Hackett, M.L.; Olavarría, V.V; Muñoz Venturelli, P.; Brunser, A.; Peng, B.; Cui, L.; Song, L.; Rogers, K.; Middleton, S.; Lim, J.Y.; Forshaw, D.; Lightbody, C.E.; Woodward, M.; Pontes-Neto, O.; de Silva, H.A.; Lin, R.T.; Lee, T.H.; Pandian, J.D.; Mead, G.E.; Robinson, T.; Watkins, C.; Headpost Investigators and Coordinators
BACKGROUND: The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS: In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS: The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P<0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P=0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P=0.83). There were no significant between-group differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS: Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours. (Funded by the National Health and Medical Research Council of Australia; HeadPoST ClinicalTrials.gov number, NCT02162017 .).
INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial
(BioMed Central, London, 2021) Song, L.; Hu, X.; Ma, L.; Chen, X.; Ouyang, M.; Billot, L.; Li, Q.; Muñoz-Venturelli, P.; Abanto, C.; Pontes-Neto, O.M.; Antonio, A.; Wasay, M.; de Silva, A.; Thang, N.H.; Pandian, J.D.; Wahab, K.W.; You, C.; Anderson, C.S.
Background: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. Methods: INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1-7.8 mmol/L and 7.8-10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. Discussion: As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established.
The third intensive care bundle with blood pressure reduction in acute cerebral haemorrhage trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial
(Elsevier, 2023) Ma, L.; Hu, X.; Song, L.; Chen, X.; Ouyang, M.; Billot, L.; Li, Q.; Malavera, A.; Li, X.; Muñoz-Venturelli, P.; de Silva, A.; Thang, N.H.; Wahab, K.W.; Pandian, J.D.; Wasay, M.; Pontes-Neto, O.M.; Abanto, C.; Arauz, A.; Shi, H.; Tang, G.; Zhu, S.; She, X.; Liu, L.; Sakamoto, Y.; You, S.; Han, Q.; Crutzen, B.; Cheung, E.; Li, Y.; Wang, X.; Chen, C.; Liu, F.; Zhao, Y.; Li, H.; Liu, Y.; Jiang, Y.; Chen, L.; Wu, B.; Liu, M.; Xu, J.; You, C.; Anderson, C.S.; INTERACT3 Investigators
BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.