Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Hur ser möjligheten ut för att anpassa befintliga tak till gröna tak med våtmark?

Våtmarkstak är en typ av extensiva gröna tak med våtmarks- eller träskväxter planterade i växtbädden. Syftet med studien är att undersöka om befintliga tak kan anpassas till gröna tak med våtmark samt visa vilka för- och nackdelar grönt tak med våtmark har jämfört med traditionella gröna tak utan våtmark. Detta leder till studiens frågeställning: ”Hur ser möjligheten ut för att anpassa befintliga tak till gröna tak med våtmark?”. Studien har sin bas i litteraturstudie med stöd av intervjuer och överslagsberäkningar. Den största fördelen med våtmarkstak jämfört med sedum- och mosstak är förmågan att ta upp mer dagvatten och att de har en rikare biotop. Det finns dock en nackdel som särskiljer sig jämfört med de andra gröna taken och det är risken för läckage. Eftersom våtmarkstaken kan hålla så mycket vatten kan en läcka bli mycket kostsam. De flesta byggnader kan anpassas för att klara att bära upp lasterna från ett våtmarkstak. Anpassningen för våtmarkstak kan bara göras på tak med en befintlig taklutning som inte överstiger 15 grader.Wetland roofs are a type of extensive green roofs with wetland or marsh plants planted in the plant bed. The aim of the study is to investigate whether existing roofs can be adapted to green roofs with wetlands and show the pros and cons of green roofs with wetlands compared with traditional green roofs without wetlands. This leads to the study's question: "How is the ability to adapt existing roofs to green roofs with wetlands?". The study is based on a literature study with the support of interviews and rough estimates. The biggest advantage of wetland roofs compared to sedum and moss roofs is the ability to absorb more stormwater and have a richer biotope. However, there is a disadvantage that differs from the other green roofs and that is the risk of leakage. Since the wetland roof can hold so much water, a leak can be very costly. Most buildings can be adapted to be able to carry the loads from a wetland roof. The adaptation for wetland roofs can only be done with an existing roof slope that does not exceed 15 degrees

Hur ser möjligheten ut för att anpassa befintliga tak till gröna tak med våtmark?

Våtmarkstak är en typ av extensiva gröna tak med våtmarks- eller träskväxter planterade i växtbädden.Syftet med studien är att undersöka om befintliga tak kan anpassas till gröna tak med våtmark samt visa vilka för- och nackdelar grönt tak med våtmark har jämfört med traditionella gröna tak utan våtmark.Detta leder till studiens frågeställning: ”Hur ser möjligheten ut för att anpassa befintliga tak till gröna tak med våtmark?”.Studien har sin bas i litteraturstudie med stöd av intervjuer och överslagsberäkningar.Den största fördelen med våtmarkstak jämfört med sedum- och mosstak är förmågan att ta upp mer dagvatten och att de har en rikare biotop. Det finns dock en nackdel som särskiljer sig jämfört med de andra gröna taken och det är risken för läckage. Eftersom våtmarkstaken kan hålla så mycket vatten kan en läcka bli mycket kostsam.De flesta byggnader kan anpassas för att klara att bära upp lasterna från ett våtmarkstak. Anpassningen för våtmarkstak kan bara göras på tak med en befintlig taklutning som inte överstiger 15 grader.Wetland roofs are a type of extensive green roofs with wetland or marsh plants planted in the plant bed.The aim of the study is to investigate whether existing roofs can be adapted to green roofs with wetlands and show the pros and cons of green roofs with wetlands compared with traditional green roofs without wetlands.This leads to the study's question: "How is the ability to adapt existing roofs to green roofs with wetlands?".The study is based on a literature study with the support of interviews and rough estimates.The biggest advantage of wetland roofs compared to sedum and moss roofs is the ability to absorb more stormwater and have a richer biotope. However, there is a disadvantage that differs from the other green roofs and that is the risk of leakage. Since the wetland roof can hold so much water, a leak can be very costly.Most buildings can be adapted to be able to carry the loads from a wetland roof. The adaptation for wetland roofs can only be done with an existing roof slope that does not exceed 15 degrees

Reverse Genomics: Design of Universal Epitope Sets to Isolate All Saccharibacteria Members from the Human Oral Cavity

International audienceMicroorganisms not yet cultured represent a large proportion of the microbes described to date. Progress in sequencing and metagenomic tools continues to increase microbial diversity without providing information on their physiological and pathophysiological characteristics, such as the recent discovery of enigmatic microbes belonging to Candidate Phyla Radiation (CPR). Reverse genomics is a recent technique allowing co-cultivation of a few CPR members, affiliated to the Saccharibacteria phylum, based on the analysis of their already-available genomes. Here, our aim is to designate a common system capable of cultivating any given taxon of this phylum from human samples. We managed to design, in silico, 11 common epitopes for all Saccharibacteria species recovered from the human oral cavity and which can serve as antigens via bioinformatics analyses. These sequences allow the synthesis of target antibodies, sorting Saccharibacteria spp. by flow cytometry and co-culturing them afterwards with adapted hosts. This epitope set can facilitate the cultivation of CPR in general, which in recent years has been considered a challenge for microbiologists, and subsequently contributes to better studying this new branch on the tree of life

Small and Equipped: the Rich Repertoire of Antibiotic Resistance Genes in Candidate Phyla Radiation Genomes

International audienceTo our knowledge, this study is one of the few studies that characterize the defense systems in the CPR group and describes the first repertoire of antibiotic resistance (AR) genes. The use of a BLAST approach with lenient criteria followed by a careful examination of the functional domains has yielded a variety of enzymes that mainly give three different mechanisms of action of resistance