Update to the effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial

Abstract: Background: MYRIAD (My Resilience in Adolescence) is a superiority, parallel group, cluster randomised controlled trial designed to examine the effectiveness and cost-effectiveness of a mindfulness training (MT) programme, compared with normal social and emotional learning (SEL) school provision to enhance mental health, social-emotional-behavioural functioning and well-being in adolescence. The original trial protocol was published in Trials (accessible at https://doi.org/10.1186/s13063-017-1917-4). This included recruitment in two cohorts, enabling the learning from the smaller first cohort to be incorporated in the second cohort. Here we describe final amendments to the study protocol and discuss their underlying rationale. Methods: Four major changes were introduced into the study protocol: (1) there were changes in eligibility criteria, including a clearer operational definition to assess the degree of SEL implementation in schools, and also new criteria to avoid experimental contamination; (2) the number of schools and pupils that had to be recruited was increased based on what we learned in the first cohort; (3) some changes were made to the secondary outcome measures to improve their validity and ability to measure constructs of interest and to reduce the burden on school staff; and (4) the current Coronavirus Disease 2019 (SARS-CoV-2 or COVID-19) pandemic both influences and makes it difficult to interpret the 2-year follow-up primary endpoint results, so we changed our primary endpoint to 1-year follow-up. Discussion: These changes to the study protocol were approved by the Trial Management Group, Trial Steering Committee and Data and Ethics Monitoring Committees and improved the enrolment of participants and quality of measures. Furthermore, the change in the primary endpoint will give a more reliable answer to our primary question because it was collected prior to the COVID-19 pandemic in both cohort 1 and cohort 2. Nevertheless, the longer 2-year follow-up data will still be acquired, although this time-point will be now framed as a second major investigation to answer some new important questions presented by the combination of the pandemic and our study design. Trial registration: International Standard Randomised Controlled Trials ISRCTN86619085. Registered on 3 June 2016

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648

The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial

STUDY OBJECTIVE: Epistaxis is a common emergency department (ED) presentation and, if simple first aid measures fail, can lead to a need for anterior nasal packing. Tranexamic acid is an agent that contributes to blood clot stability. The aim of this study is to investigate the effectiveness of topical intranasal tranexamic acid in adult patients presenting to the ED with persistent epistaxis, and whether it reduces the need for anterior nasal packing. METHODS: From May 5, 2017, to March 31, 2019, a double-blind, placebo-controlled, multicenter, 1:1, randomized controlled trial was conducted across 26 EDs in the United Kingdom. Participants with spontaneous epistaxis, persisting after simple first aid and the application of a topical vasoconstrictor, were randomly allocated to receive topical tranexamic acid or placebo. The primary outcome was the need for anterior nasal packing of any kind during the index ED attendance. Secondary outcome measures included hospital admission, need for blood transfusion, recurrent epistaxis, and any thrombotic events requiring any hospital reattendance within 1 week. RESULTS: The study sample consisted of 496 participants with spontaneous epistaxis, persisting after simple first aid and application of a topical vasoconstrictor. In total, 211 participants (42.5%) received anterior nasal packing during the index ED attendance, including 111 of 254 (43.7%) in the tranexamic acid group versus 100 of 242 (41.3%) in the placebo group. The difference was not statistically significant (odds ratio 1.107; 95% confidence interval 0.769 to 1.594; P=.59). Furthermore, there were no statistically significant differences between tranexamic acid and placebo for any of the secondary outcome measures. CONCLUSION: In patients presenting to an ED with atraumatic epistaxis that is uncontrolled with simple first aid measures, topical tranexamic acid applied in the bleeding nostril on a cotton wool dental roll is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing.Not heldPublished version, accepted version (12 month embargo

International Ocean Discovery Program Expedition 369 Preliminary Report: Australia Cretaceous Climate and Tectonics: Tectonic, paleoclimate, and paleoceanographic history of high-latitude southern margins of Australia during the Cretaceous

The tectonic and paleoceanographic setting of the Great Australian Bight (GAB) and the Mentelle Basin (MB; adjacent to Naturaliste Plateau) offered an outstanding opportunity to investigate Cretaceous and Cenozoic climate change and ocean dynamics during the last phase of breakup among remnant Gondwana continents. Sediment recovered from sites in both regions during International Ocean Discovery Program Expedition 369 will provide a new perspective on Earth\u27s temperature variation at sub-polar latitudes (60°-62°S) across the extremes of the mid-Cretaceous hot greenhouse climate and the cooling that followed. The primary goals of the expedition were to: * Investigate the timing and causes for the rise and collapse of the Cretaceous hot greenhouse climate and how this climate mode affected the climate-ocean system and oceanic biota; * Determine the relative roles of productivity, ocean temperature, and ocean circulation at high southern latitudes during Cretaceous oceanic anoxic events (OAEs); * Identify the main source regions for deep-water and intermediate-water masses in the southeast Indian Ocean and how these changed during Gondwana breakup; * Characterize how oceanographic conditions at the MB changed during the Cenozoic opening of the Tasman Passage and restriction of the Indonesian Gateway; * Resolve questions on the volcanic and sedimentary origins of the Australo-Antarctic Gulf and Mentelle Basin and provide stratigraphic control on the age and nature of the prebreakup successions. Hole U1512A in the GAB recovered a 691 m thick sequence of black claystone ranging from the early Turonian to the early Campanian. Age control is primarily based on calcareous nannofossils, but the presence of other microfossil groups provided consistent but low-resolution control. Despite the lithologic uniformity, long- and short-term variations in natural gamma ray and magnetic susceptibility intensities show cyclic alternations that suggest an orbital control of sediment deposition that will be useful for developing an astrochronology for the sequence. Sites U1513-U1516 were drilled between 850 and 3900 m water depth in the MB and penetrated 774, 517, 517, and 542 meters below seafloor (mbsf), respectively. Under a thin layer of Pleistocene-upper Miocene sediment, Site U1513 cored a succession of Cretaceous units from the Campanian to the Valanginian. Site U1514 sampled an expanded Pleistocene-Eocene sequence and terminated in the upper Albian. The Cenomanian-Turonian interval at Site U1514 recovered deformed sedimentary rocks that probably represent a detachment zone. Site U1515 is located on the west Australian margin at 850 m water depth and was the most challenging site to core because much of the upper 350 m was either chert or poorly consolidated sand. However, the prebreakup Jurassic(?) sediments interpreted from the seismic profiles were successfully recovered. Site U1516 cored an expanded Pleistocene, Neogene, and Paleogene section and recovered a complete Cenomanian/Turonian boundary interval containing five layers with high total organic carbon content. The Early Cretaceous volcanic rocks and underlying Jurassic(?) sediments cored in different parts of the MB provide information on the timing of different stages of the Gondwana breakup. The recovered cores provide sufficient new age constraints to underpin a reevaluation of the basin-wide seismic stratigraphy and tectonic models for the region

Early Cretaceous subsidence of the Naturaliste Plateau defined by a new record of volcaniclastic-rich sequence at IODP Site U1513

International audienceThe Naturaliste Plateau is a submarine continental ribbon rifted from the southwest Australian margin during the Early Cretaceous breakup of East Gondwana. It occupied a key position near the juncture of Greater India and the boundary between Australia and Antarctica. However, details of the Early Cretaceous evolution of the plateau are not well known because of limited data. Drilling at Site U1513 during IODP Expedition 369 recovered the first complete Lower Cretaceous succession on the eastern Naturaliste Plateau. The succession includes syn-rift volcanic rocks, Hauterivian to early Aptian volcaniclastic-rich sedimentary rocks, and Albian claystone strata. The 235-m thick volcaniclastic-rich sequence represents the missing post-breakup record in the southwest Australian rifted margin. It spans the transition from syn- to post-rift phase during the final stages of breakup between Greater India and Australia-Antarctica. We report the lithological, petrophysical, geochemical, paleontological, and paleomagnetic characteristics of the sequence, and then synthesize the results to define the Early Cretaceous depositional environment and subsidence history of the Naturaliste Plateau. From the early Hauterivian, weathered volcanic products were eroded and re-deposited locally as a volcaniclastic-rich sequence, with a major contribution from the southern Naturaliste Plateau. The depositional environment evolved from a shelf to upper bathyal condition during the Hauterivian through early Barremian with a decreasing sedimentation rate. This period is defined as a late syn-rift subsidence phase by NW-SE trending extension. After the final breakup with Greater India, the plateau remained at upper bathyal depths with little deposition until the early Aptian. Mid–lower bathyal depths inferred from the Albian claystone strata suggest that the post-rift thermal subsidence commenced during the late Aptian. This two-phase post-rift subsidence reflects the proximity or high temperature of mantle plume, possibly the Kerguelen plume, and its westward migration relative to the southwest Australian rifted margin