Child witness expressions of certainty are informative

Peer reviewe

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

PMS2 and its role in mismatch repair deficiency syndrome

The PMS2 protein IS a component of the post-replicative DNA mismatch repair (MMR) system, which acts to correct mispaired nucleotides and small insertion-deletion loops in new DNA duplexes. Biallelic mutations in any of several MMR genes result in a deficiency syndrome (MMR-D) that predisposes to childhood cancer. However, mutation detection in PMS2 is complicated by the existence of multiple pseudo genes; furthermore, gene conversion events generate sequence exchange between gene and pseudogene. The main laboratory marker of defective MMR is microsatellite instability (MSI), but this is not easily demonstrated in constitutional DNA using existing methods. A novel assay is described here, that identifies germline MS! in patients with homozygous mutations in MMR genes; this method allows the degree of instability to be quantified as a measure termed the gMSI ratio. Using this tool, a UK childhood leukaemia DNA bank, comprising 799 patients, from the ALL-97 trial has been screened for gMSI, demonstrating that mutations in MMR genes are not a frequent cause of sporadic acute lymphoblastic leukaemia in children. A population study of sequence variation at the PMS2 and PMS2CL loci has been performed, by sequencing 18 PMS2 and 29 PMS2CL alleles, revealing eight novel non-synonymous polymorphic variants in exon 11 of PMS2, and one in each ofexons 13 and 14. Three patches ofintronic sequence (76 to 258 nucleotides long) are identified, which show evidence of gene conversion between gene and pseudogene. Single nucleotide polymorph isms and paralogous sequence variants in PMS2 and PMS2CL are defined which will aid future mutation detection. The p.R802X mutation in PMS2 is a founder mutation, which ill the homozygous state is the commonest cause of MMR-D syndrome in British Pakistani patients. An EBV -transformed lymphoblastoid cell line homozygous for p.R802X has been used to investigate whether PTC124 (Ataluren), a drug promoting read through of premature termination codons, might be of benefit in alleviating the effects of this mutation. In this exploratory study, treatment with PTC124 led to no change in PMS2 mRNA expression and no production of full-length PMS2 protein, suggesting no successful readthrough of the p.R802X mutation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Dataset for: Impact of age of exposure and emotional reaction to Sexually Explicit material on longer-term mental health and relationship satisfaction

Two data sets, one for test-retest of the impact of SEM questionnaire developed for the study and one for the Main Research Study -variables based on Impact of SEM Questionnaire (developed for the study), Mental Health outcomes, Relationship satisfaction and Life Events for thesis titled &quot;Associations between initial exposure to Sexually Explicit Material, Mental Health and self-perceived Relationship Satisfaction.&quot;. These datasets support Doctoral Thesis &quot;Associations between initial exposure to Sexually Explicit Material, Mental Health and self-perceived Relationship Satisfaction&quot; University of Southampton September 2020. The dataset can be requested via https://library.soton.ac.uk/datarequest by bonefide researchers with ethical approval.</span

Audit of heart failure management amongst geriatric patients

Poster presentation: Aim: Congestive cardiac failure is associated with significant morbidity and mortality. The National Heart Foundation and Cardiac Society of Australia and New Zealand detail best-practice heart failure (HF) management. (Krum et al. MJA, 2011; 194:8)We audited compliance with same within our geriatric department. Method: Initial audit included 31 HF patients admitted Dec 2012-April 2013. We assessed 10 best-practice HF management items (ECHO [≤1 year], blood count, electrolytes, thyroid function tests [TFT], chest X-ray, ECG, diagnosis confirmation, medications review, referral to community HF team, patient education), and employment of a ‘best practice’ HF checklist stamp. Results: Overall, rates of compliance were- ECHO: 58% (14/31), 92% HF medication review, TFT: 42% (10/31), chest X-ray and ECG: 96%, diagnosis confirmation: 40%, community team referral: 73%, documented education: 17%. None received all 10 best-practice interventions

Child Witness Expressions of Certainty are Informative

Children are frequently witnesses of crime. In the witness literature and legal systems, children are often deemed to have unreliable memories. Yet, in the basic developmental literature, young children can monitor their memory. To address these contradictory conclusions, we reanalysed the confidence-accuracy relationship in basic and applied research. Confidence provided considerable information about memory accuracy, from at least age 8, but possibly younger. We also conducted an experiment where children in young- (4–6 years), middle- (7–9 years), and late- (10–17 years) childhood (N=2,205) watched a person in a video, and then identified that person from a police lineup. Children provided a confidence rating (an explicit judgement), and used an interactive lineup—in which the lineup faces can be rotated—and we analyzed children’s viewing behavior (an implicit measure of metacognition). A strong confidence-accuracy relationship was observed from age 10, and an emerging relationship from age 7. A constant likelihood ratio signal-detection model can be used to understand these findings. Moreover, in all ages, interactive viewing behavior differed in children who made correct versus incorrect suspect identifications. Our research reconciles the apparent divide between applied and basic research findings and suggests that the fundamental architecture of metacognition that has previously been evidenced in basic list-learning paradigms also underlies performance on complex applied tasks. Contrary to what is believed by legal practitioners, but similar to what has been found in the basic literature, identifications made by children can be reliable when appropriate metacognitive measures are used to estimate accuracy