Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Background: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. Methods: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. Findings: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two ( Interpretation: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis.</div

Cognitive impairment and cardiovascular medication use: Results from wave 1 of The Irish Longitudinal Study on Ageing.

AIM: To explore the association between cardiovascular medication use and cognitive impairment in adults aged 50 years and over. METHOD: This cross-sectional linked database study involved secondary quantitative analysis of 1903 participants from wave 1 of the Irish Longitudinal Study on Ageing with available pharmacy claims data. Cognitive impairment was assessed using a cut-off of ≤23 on the Montreal Cognitive Assessment. Cardiovascular medication use was calculated using the proportion of days covered for antihypertensive, antithrombotic, and lipid-modifying medications. For each class of cardiovascular medication, participants were categorized as belonging to one of three medication use groups: (1) not dispensed any medications (reference); (2) poor adherence (proportion of days covered RESULTS: Controlling for demographic and health variables, there was no evidence of an independent association between impaired cognitive function and use of antihypertensives [good adherence OR (95% CI): 1.16 (0.88, 1.52), poor adherence OR (95% CI): 1.39 (0.95, 2.04)]; antithrombotics [good adherence OR (95% CI): 1.26 (0.93, 1.70), poor adherence OR 95% CI): 1.13 (0.80, 1.59)]; or lipid-modifying agents [good adherence OR (95% CI): 0.95 (0.71, 1.25), poor adherence OR (95% CI): 0.88 (0.64, 1.22)]. CONCLUSION: We found no evidence of an association between cardiovascular medication use and cognitive function. Future studies should investigate the prospective associations between cognition and use of cardiovascular medications using longitudinal data.</p

Can a media campaign change health service use in a population with stroke symptoms? Examination of the first Irish stroke awareness campaign.

BACKGROUND: Mass media campaigns for stroke awareness encourage the public to recognise stroke symptoms and respond to stroke in a timely manner. However, there is little evidence to suggest that media messages can influence behaviour after stroke onset. The F.A.S.T. (Face Arm Speech Time) test is a common stroke recognition tool used in public education campaigns. OBJECTIVE: To assess the impact of the F.A.S.T. campaign on health service use in Ireland, which has had no previous exposure to a F.A.S.T. media campaign. METHODS: An interrupted time series design was used to detect behaviour change after the introduction of the first Irish F.A.S.T. campaign in presentations of patients with suspected stroke to two emergency departments (EDs), serving a population of about 580 000. RESULTS: There was a significant change in ED attendance of patients with reported stroke symptoms after the introduction of the F.A.S.T. campaign (β=0.84, 95% CI 0.43 to 1.24; p CONCLUSIONS: This first Irish F.A.S.T. campaign had an initial impact on ED attendance of patients with stroke symptoms. However, the campaign effects were not sustained in the long term. Results indicate that prehospital delay in accessing acute stroke services is a complex process with involvement of factors other than stroke knowledge and intention to call 911.</p

Diagnostic and prognostic circulating microRNA in acute stroke: a systematic and bioinformatic analysis of current evidence

Background and Purpose Stroke is the second leading cause of death and disability worldwide and its diagnosis, and assessment of prognosis, remains challenging. There is a need for improved diagnostic and prognostic biomarkers. MicroRNAs (miRNAs) play important roles in the post-transcriptional regulation of gene expression and their secretion and remarkable stability in biofluids highlights their potential as sensitive biomarkers in the diagnosis and prognosis of acute stroke. Methods We carried out a systematic review to assess current evidence supporting the potential of miRNAs to act as unique diagnostic and prognostic biomarkers in blood samples collected from patients suffering acute stroke within 24 hours of symptoms onset. Results We identified 22 studies eligible for inclusion with 33 dysregulated miRNAs having diagnostic potential in the acute phase of the disease. We identified miR-16, miR-126, and miR-335 as having the highest sensitivity as diagnostic and prognostic biomarkers in acute ischaemic stroke and present original bioinformatic and pathway enrichment analysis of putative miRNA–target interactions. Conclusions miRNAs represent unique biomarkers which have a promising future in stroke diagnosis and prognosis. However, there is a need for more standardized and consistent methodology for the accurate interpretation and translation of miRNAs as novel specific and sensitive biomarkers into clinical practice</p

Anticholinergic and sedative drug burden in community-dwelling older people: a national database study.

OBJECTIVES: The Drug Burden Index (DBI) tool quantifies individual exposure to anticholinergic and sedative medications. The DBI has been internationally validated against adverse health outcomes in older people. DBI exposure has not been reported in the Irish older population. This study aimed to: (1) develop a list of drugs with clinically significant anticholinergic and/or sedative effects (DBI medications) relevant to Ireland; (2) examine, using the DBI formula, the prevalence of exposure to DBI medications in Irish older people and (3) explore patient factors associated DBI exposure. DESIGN: A cross-sectional national pharmacy claims database study. SETTING: Community setting using the General Medical Services (GMS) scheme pharmacy claims database maintained by the Health Service Executive Primary Care Reimbursement Services. PARTICIPANTS: Irish older individuals (aged ≥65 years) enrolled in the GMS scheme and dispensed at least one prescription item in 2016 (n=428 516). MAIN OUTCOME MEASURES: Prevalence of exposure to DBI medications and patient factors associated with DBI exposure. RESULTS: 282 874 (66%) of the GMS population aged ≥65 years were exposed to at least one DBI medication in 2016. Prevalence of exposure to DBI medications was significantly higher in females than males (females 71.6% vs males 58.7%, adjusted OR 1.65, 95% CI 1.63 to 1.68). Prevalence of DBI exposure increased progressively with the number of chronic drugs used, rising from 42.7% of those prescribed 0-4 chronic drugs to 95.4% of those on ≥12 chronic drugs (adjusted OR 27.8, 95% CI 26.7 to 29.0). The most frequently used DBI medications were codeine/paracetamol combination products (20.1% of patients), tramadol (11.5%), zopiclone (9.5%), zolpidem (8.5%), pregabalin (7.9%) and alprazolam (7.8%). CONCLUSIONS: The majority of older people in Ireland are exposed to medications with anticholinergic and/or sedative effects, particularly females and those with multiple comorbidities. The high use of low-dose codeine/paracetamol combination products, Z-drugs and benzodiazepines, suggests there are opportunities for deprescribing.</p

The Irish National Adverse Event Study-2 (INAES-2): longitudinal trends in adverse event rates in the Irish healthcare system

Objectives: To quantify the prevalence and nature of adverse events in acute Irish hospitals in 2015 and to assess the impact of the National Clinical Programmes and the National Clinical Guidelines on the prevalence of adverse events by comparing these results with the previously published data from 2009.Design and methods: A retrospective chart review of 1605 admissions to eight Irish hospitals in 2015, using identical methods to those used in 2009.Results: The percentage of admissions associated with one or more adverse events was unchanged (p=0.48) at 14% (95% CI=10.4% to 18.4%) in 2015 compared with 12.2% (95% CI=9.5% to 15.5%) in 2009. Similarly, the prevalence of preventable adverse events was unchanged (p=0.3) at 7.4% (95% CI=5.3% to 10.5%) in 2015 compared with 9.1% (95% CI=6.9% to 11.9%) in 2009. The incidence densities of preventable adverse events were 5.6 adverse events per 100 admissions (95% CI=3.4 to 8.0) in 2015 and 7.7 adverse events per 100 admissions (95% CI=5.8 to 9.6) in 2009 (p=0.23). However, the percentage of preventable adverse events due to hospital-associated infections decreased to 22.2% (95% CI=15.2% to 31.1%) in 2015 from 33.1% (95% CI=25.6% to 41.6%) in 2009 (p=0.01).Conclusion: Adverse event rates remained stable between 2009 and 2015. The percentage of preventable adverse events related to hospital-associated infection decreased, which may represent a positive impact of the related national programmes and guidelines.</p

National and institutional trends in adverse events over time: a systematic review and meta-analysis of longitudinal retrospective patient record review studies

Objective: This study aimed to determine if the implementation of large-scale patient safety initiatives have been successful in reducing overall and preventable adverse event rates in hospital inpatients.Design: The design used in this study was systematic review and meta-analysis.Data resources: We followed our published protocol (PROSPERO [CRD42019140058]) and searched the following databases: PubMed, CINAHL, PsycINFO, Cochrane Library, and Embase from inception to February 2020. The reference lists of eligible studies were also searched.Eligibility: All longitudinal retrospective record review studies that examined adverse event rates before and after the introduction of patient safety initiatives in hospital inpatients were included.Data extraction: Data extraction, quality, and risk of bias assessment were carried out by 2 independent reviewers. Information on study design, setting, demographics, interventions, and safety outcome measures was extracted.Results: A total of 3894 articles were screened, and 7 articles met the eligibility criteria for our systematic review with 5 of these providing sufficient information for inclusion in the meta-analysis. The degree of heterogeneity was high among studies. The meta-analysis demonstrated a minimal risk reduction in overall adverse event rates of 0.017 (95% confidence interval, 0.002-0.032) when the lower-quality studies were excluded, with one adverse event being prevented for every 59 hospital admissions.Conclusions: These findings are significant when the large numbers of admissions to a hospital every year are considered. Given the low numbers of large-scale implementation studies, there is a need for more research on the effectiveness of patient safety initiatives to further assess the impact of such initiatives on adverse events.</p

‘What effect do safety culture interventions have on health care workers in hospital settings?’ A systematic review of the international literature [version 1; peer review: 2 approved with reservations]

Introduction: Interventions designed to improve safety culture in hospitals foster organisational environments that prevent patient safety events and support organisational and staff learning when events do occur. A safety culture supports the required health workforce behaviours and norms that enable safe patient care, and the well-being of patients and staff. The impact of safety culture interventions on staff perceptions of safety culture and patient outcomes has been established. To-date, however, there is no common understanding of what staff outcomes are associated with interventions to improve safety culture and what staff outcomes should be measured.  Objectives: The study seeks to examine the effect of safety culture interventions on staff in hospital settings, globally. The research questions are: 1) what effects do interventions to improve safety culture have on staff? 2) What intervention features, safety culture domains or other factors explain these effects? 3) What staff outcomes and experiences are identified? Methods and Analysis: A mixed methods systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches will be conducted using the electronic databases of MEDLINE, EMBASE, CINAHL, Health Business Elite, and Scopus. Returns will be screened in Covidence according to inclusion and exclusion criteria. The mixed-methods appraisal tool (MMAT) will be used as a quality assessment tool. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials and non-randomised studies of interventions will be employed to verify bias. Synthesis will follow the Joanna Briggs Institute methodological guidance for mixed methods reviews, which recommends a convergent approach to synthesis and integration. Discussion: This systematic review will contribute to the international evidence on how interventions to improve safety culture may support staff outcomes and how such interventions may be appropriately designed and implemented.</p

Short-term air pollution as a risk for stroke admission: a time-series analysis

Background: The harmful effects of outdoor air pollution on stroke incidence are becoming increasingly recognised. We examined the impact of different air pollutants (PM2.5, PM10, NO2, ozone, and SO2) on admission for all strokes in two Irish urban centres from 2013 to 2017.Methods: Using an ecological time series design with Poisson regression models, we analysed daily hospitalisation for all strokes and is-chaemic stroke by residence in Dublin or Cork, with air pollution level monitoring data with a lag of 0-2 days from exposure. Splines of temperature, relative humidity, day of the week, and time were included as confounders. Analysis was also performed across all four seasons. Data are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range (IQR) increase in each pollutant.Results: There was no significant association between all stroke admission and any individual air pollutant. On seasonal analysis, during winter in the larger urban centre (Dublin), we found an association between all stroke cases and an IQR increase in NO2 (RR 1.035, 95% CI: 1.003-1.069), PM10 (RR 1.032, 95% CI: 1.007-1.057), PM2.5 (RR 1.024, 95% CI: 1.011-1.039), and SO2 (RR 1.035, 95% CI: 1.001-1.071). There was no significant association found in the smaller urban area of Cork. On meta-analysis, there remained a significant association between NO2 (RR 1.013, 95% CI: 1.001-1.024) and PM2.5 (1.009, 95% CI 1.004-1.014) per IQR increase in each.Discussion: Short-term air pollution in winter was found to be associated with hospitalisation for all strokes in a large urban centre in Ireland. As Ireland has relatively low air pollution internationally, this highlights the need to introduce policy changes to reduce air pollution in all countries.</p

Adverse Drug reactions in an Ageing PopulaTion (ADAPT) study protocol: a cross-sectional and prospective cohort study of hospital admissions related to adverse drug reactions in older patients.

INTRODUCTION: Older people experience greater morbidity with a corresponding increase in medication use resulting in a potentially higher risk of adverse drug reactions (ADRs). The aim of this study is to determine the prevalence and characteristics of ADR-related hospital admissions among older patients (≥65 years) and their associated health and cost outcomes. METHODS AND ANALYSIS: The proposed study will include a cross-sectional study of ADR prevalence in all patients aged ≥65 years admitted acutely to a large tertiary referral hospital in Ireland over a 9-month period (2016-2017) and a prospective cohort study of patient-reported health outcomes and costs associated with ADR-related hospital admissions. All acute medical admissions will be screened for a suspected ADR-related hospital admission. A number of validated algorithms will be applied to assess the type, causative medications, preventability and severity of each ADR. ADRs will be determined, using a consensus method, by an expert panel. Patients who provide consent will be followed up 3 months post-discharge to establish patient-reported health outcomes (health service use, health-related quality of life, adherence) and costs associated with ADR-related hospital admissions. A random sample of patients admitted to hospital without a suspected ADR will be invited to take part in the study as a control group. ETHICS AND DISSEMINATION: Ethical approval was obtained from Beaumont Hospital Ethics Committee. Findings will be disseminated through presentations and peer-reviewed publications.</p