Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

Background Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. Methods This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). Results Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]). Interpretation Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. Funding National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme)

Sustainable architectural design studio towards the development of creative learning environment

The design studio has always been the key feature of architecture education. Unfortunately, the design studio in universities focused too much on cost and the uniformity of design throughout the whole campus and this leads to office-like layout which is designed without taking note on the psychological approach of the architecture students using the spaces. This paper intends to elucidate this problem and tries to find the best design solution for a sustainable architectural design studio towards an effective studio learning outcome vital for a creative learning environment. This study has found out that there are three key factors that contributed in the development of creative studio learning environment among occupants which are—the needs to have a transformable private and personal space, multi-functional interactive space and livable natural setting. This study is important because suitable architectural studio will not only provide a creative learning environment to the users but also established referential guideline for future architects

Building communal values for quality sustainable living in traditional madrassa—the case of Madrassa Quran Kubang Bujuk, Trengganu

Madrassa is deemed referred as a religious education center for the Muslim community. Due to its well acceptance and establishment in the Muslim society, madrassa not only acts as scholarly center but also as a place that promotes goodwill and unity. However, many scholars are of opinion that traditional madrassa is considerably significant as it has an important role in reshaping Islamic education towards the development of communal values. This paper aims to identify and elucidate the importance of the traditional design of madrassa towards the development of communal values. Madrassa Quran Kubang Bujuk in Trengganu was analyzed as case study due to its significant establishment and dominant role in reshaping the local Muslim society. In addition, the architectural madrassa design is distinctive, and its multifunctional purpose considers the well-being of occupants towards the development of communal values. Semiotic as research method is used to reveal the communal values that are embedded in the architectural design of a madrassa. The findings will benefits future designers and scholars on the importance of communal values and the propagation of Islamic teaching through the representation of madrassa as built form

Species composition and distribution pattern of stingrays in the coastal waters of Terengganu, Malaysia, the South China Sea

Stingrays are part of commercial fisheries worldwide; Malaysia is ranked as the eighth-largest stingray fishery in the world. Samples were collected monthly from January 2018 to December 2018 using stingray gill nets in Coastal South China seawaters of Terengganu. The present study aimed to determine the abundance and distribution of stingrays based on species and sizes at different habitat and seasons in the Terengganu, Malaysia coastal waters. A total of 10 stingray species were collected from 122 samples. Stingray species are distributed differently according to habitat and seasonal. The result of a two-way ANOVA showed that habitat and season significantly affect the abundance of stingrays (P < 0.001). Most catches were in 20 m depth during the dry season. The result of a non-metric multidimensional scaling ordination indicates that the grouping overlapped in habitat and season with similar species collected

Effects of Different Degrees of Cataract on the Multifocal Electroretinogram

2003-2004 > Academic research: refereed > Publication in refereed journa

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study.

BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.status: publishe

Age-related change in fast adaptation mechanisms measured with the scotopic full-field ERG

PURPOSE: To quantify the response dynamics of fast adaptation mechanisms of the scotopic ERG in younger and older adults using full-field m-sequence flash stimulation. METHODS: Scotopic ERGs were measured for a series of flashes separated by 65 ms over a range of 260 ms in 16 younger (20–26, 22.2 ± 2.1; range mean ±1 SD) and 16 older (65–85, 71.2 ± 7) observers without retinal pathology. A short-wavelength (λ(peak) = 442 nm) LED was used for scotopic stimulation, and the flashes ranged from 0.0001 to 0.01 cd s m(−2). The complete binary kernel series was derived from the responses to the m-sequence flash stimulation, and the first- and second-order kernel responses were analyzed. The first-order kernel represented the response to a single, isolated flash, while the second-order kernels reflected the adapted flash responses that followed a single flash by one or more base intervals. B-wave amplitudes of the adapted flash responses were measured and plotted as a function of interstimulus interval to describe the recovery of the scotopic ERG. A linear function was fitted to the linear portion of the recovery curve, and the slope of the line was used to estimate the rate of fast adaptation recovery. RESULTS: The amplitudes of the isolated flash responses and rates of scotopic fast adaptation recovery were compared between the younger and older participants using a two-way ANOVA. The isolated flash responses and rates of recovery were found to be significantly lower in the older adults. However, there was no difference between the two age groups in response amplitude or recovery rate after correcting for age-related changes in the density of the ocular media. CONCLUSIONS: These results demonstrated that the rate of scotopic fast adaptation recovery of normal younger and older adults is similar when stimuli are equated for retinal illuminance

Aging and mfERG Topography

Aim: To study the effect of aging retina on the multifocal electroretinogram (mfERG). Methods: A total of 18 young subjects (age 18 -24 years) and 36 elderly subjects (aged 60 -85 years) with intraocular lenses (IOLs) were recruited for this study. No subjects had significant eye diseases or media opacities. mfERG was measured in standard conditions using the VERIS system (version 4.1). There were three groups of 18 subjects: (1) 18 -25 years, (2) 60-70 years, and (3) 75 -85 years. mfERG responses were grouped into central, paracentral, and peripheral regions for analysis. The N1 amplitude, P1 amplitude, N1 latency, and P1 latency of the first-order responses were analysed. Results: Age had no effect on P1 latency, N1 amplitude, and P1 amplitude; however, N1 latencies from central to peripheral regions were significantly longer for group 3 than for group 1. Conclusions: This study suggests that measured age-related decreases in mfERG responses are due to optical factors (decrease in retinal light levels, scatter) before the age of 70 years, but neural factors significantly affect mfERG topography after the age of 70 years.School of Optometr