A multicentre evaluation exploring the impact of an integrated health and social care intervention for the caregivers of ICU survivors

Background: Caregivers and family members of Intensive Care Unit (ICU) survivors can face emotional problems following patient discharge from hospital. We aimed to evaluate the impact of a multi-centre integrated health and social care intervention, on caregiver and family member outcomes. Methods: This study evaluated the impact of the Intensive Care Syndrome: Promoting Independence and Return to Employment (InS:PIRE) programme across 9 sites in Scotland. InS:PIRE is an integrated health and social care intervention. We compared caregivers who attended this programme with a contemporary control group of ICU caregivers (usual care cohort), who did not attend. Results: The primary outcome was anxiety measured via the Hospital Anxiety and Depression Scale at 12 months post-hospital discharge. Secondary outcome measures included depression, carer strain and clinical insomnia. A total of 170 caregivers had data available at 12 months for inclusion in this study; 81 caregivers attended the InS:PIRE intervention and completed outcome measures at 12 months post-hospital discharge. In the usual care cohort of caregivers, 89 completed measures. The two cohorts had similar baseline demographics. After adjustment, those caregivers who attended InS:PIRE demonstrated a significant improvement in symptoms of anxiety (OR: 0.42, 95% CI: 0.20–0.89, p = 0.02), carer strain (OR: 0.39; 95% CI: 0.16–0.98 p = 0.04) and clinical insomnia (OR: 0.40; 95% CI: 0.17–0.77 p < 0.001). There was no significant difference in symptoms of depression at 12 months. Conclusions: This multicentre evaluation has shown that caregivers who attended an integrated health and social care intervention reported improved emotional health and less symptoms of insomnia, 12 months after the delivery of the intervention

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

Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells

Abstract Background A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel “cup” cells by comparing their transcriptome to that of other cell types. Results RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells. Conclusions This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization

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

Long-term outcomes following severe COVID-19 infection: a propensity matched cohort study

Background: There are limited data describing the long-term outcomes of severe COVID-19. We aimed to evaluate the long-term psychosocial and physical consequences of severe COVID-19 for patients. Methods: We conducted a multicentre observational cohort study; between 3 and 7 months posthospital discharge, patients who had been admitted to critical care due to severe COVID-19 were invited to an established recovery service. Standardised questionnaires concerning emotional, physical and social recovery, including information on employment, were completed by patients. Using propensity score matching, we explored outcomes between patients admitted to critical care with and without COVID-19, using data from the same recovery programme. Results: Between July 2020 and December 2020, 93 patients who had been admitted to critical with COVID-19 participated. Emotional dysfunction was common: 46.2% of patients had symptoms of anxiety and 34.4% symptoms of depression. At follow-up 53.7% of previously employed patients had returned to employment; there was a significant difference in return to employment across the socio-economic gradient, with lower numbers of patients from the most deprived areas returning to employment (p=0.03). 91 (97.8%) COVID-19 patients were matched with 91 non-COVID-19 patients. There were no significant differences in any measured outcomes between the two cohorts. Interpretation: Emotional and social problems are common in survivors of severe COVID-19 infection. Coordinated rehabilitation is required to ensure patients make an optimal recovery

Developing explanatory models of health inequalities in childhood dental caries

Objective: Long-term aim is to determine optimum interventions to reduce dental caries in children in disadvantaged communities and minimise the effects of exclusion from health care systems, of ethnic diversity, and health inequalities. Design: generation of initial explanatory models, study protocol and development of two standardised measures. First, to investigate how parental attitudes may impact on their children's oral health-related behaviours and second, to assess how dentists' attitudes may impact on the provision of dental care. Subjects: Core research team, lead methodologists, 44 consortium members from 18 countries. To complete the development of the questionnaire, the initial set of items was administered to parents (n=23) with children in nursery schools in Dundee, Scotland and sent to the same parents one week later. A standardised measure examining barriers to providing dental care for children aged 3 to 6 years was developed. 20 dentists working in primary dental care in Scotland completed the measure on two different occasions separated by one week. Results: Explanatory models were developed. Family questionnaire: test-retest reliability excellent (r =0.93 p ≤ 0.001) with very good internal reliability (alpha = 0.89). Dentists questionnaire: excellent test-re-test reliability r=0.88, (alpha= 0.90). Conclusions: Interaction between consortium members enhanced the validity of the questionnaires and protocols for different cultural locations. There were challenges in developing and delivering this multi-centre study. Experience gained will support the development of substantive trials and longitudinal studies to address the considerable international health disparity of childhood dental caries.link_to_subscribed_fulltex