Stroke treatment academic industry roundtable recommendations for individual data pooling analyses in stroke

Pooled analysis of individual patient data from stroke trials can deliver more precise estimates of treatment effect, enhance power to examine prespecified subgroups, and facilitate exploration of treatment-modifying influences. Analysis plans should be declared, and preferably published, before trial results are known. For pooling trials that used diverse analytic approaches, an ordinal analysis is favored, with justification for considering deaths and severe disability jointly. Because trial pooling is an incremental process, analyses should follow a sequential approach, with statistical adjustment for iterations. Updated analyses should be published when revised conclusions have a clinical implication. However, caution is recommended in declaring pooled findings that may prejudice ongoing trials, unless clinical implications are compelling. All contributing trial teams should contribute to leadership, data verification, and authorship of pooled analyses. Development work is needed to enable reliable inferences to be drawn about individual drug or device effects that contribute to a pooled analysis, versus a class effect, if the treatment strategy combines ≥2 such drugs or devices. Despite the practical challenges, pooled analyses are powerful and essential tools in interpreting clinical trial findings and advancing clinical care

CRASH - Corticosteroid Randomisation after Significant Head Injury

A large simple placebo controlled trial, among adults with head injury and impaired consciousness, of the effects of a 48-hour infusion of corticosteroids on death and neurological disability. CRASH was a randomised, controlled, double-blind trial undertaken in 239 hospitals in 49 countries. A total of 10008 adults with head injury and a Glasgow Coma Score (GCS) of 14 or less within 8 hours of injury were randomly allocated 48 hour infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation and analysis was by intention to treat. Access to this dataset is available via https://freebird.lshtm.ac.uk/

Value of risk scores in the decision to palliate patients withruptured abdominal aortic aneurysm

Background: The aim of this study was to develop a 48‐h mortality risk score, which included morphology data, for patients with ruptured abdominal aortic aneurysm presenting to an emergency department, and to assess its predictive accuracy and clinical effectiveness in triaging patients to immediate aneurysm repair, transfer or palliative care. Methods: Data from patients in the IMPROVE (Immediate Management of the Patient With Ruptured Aneurysm: Open Versus Endovascular Repair) randomized trial were used to develop the risk score. Variables considered included age, sex, haemodynamic markers and aortic morphology. Backwards selection was used to identify relevant predictors. Predictive performance was assessed using calibration plots and the C‐statistic. Validation of the newly developed and other previously published scores was conducted in four external populations. The net benefit of treating patients based on a risk threshold compared with treating none was quantified. Results: Data from 536 patients in the IMPROVE trial were included. The final variables retained were age, sex, haemoglobin level, serum creatinine level, systolic BP, aortic neck length and angle, and acute myocardial ischaemia. The discrimination of the score for 48‐h mortality in the IMPROVE data was reasonable (C‐statistic 0·710, 95 per cent c.i. 0·659 to 0·760), but varied in external populations (from 0·652 to 0·761). The new score outperformed other published risk scores in some, but not all, populations. An 8 (95 per cent c.i. 5 to 11) per cent improvement in the C‐statistic was estimated compared with using age alone. Conclusion: The assessed risk scores did not have sufficient accuracy to enable potentially life‐saving decisions to be made regarding intervention. Focus should therefore shift to offering repair to more patients and reducing non‐intervention rates, while respecting the wishes of the patient and family

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980–2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background: Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods: For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings: By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation: After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines

A standardised protocol for neuro-endoscopic lavage for post-haemorrhagic ventricular dilatation: A Delphi consensus approach

Neuro-endoscopic lavage (NEL) has shown promise as an emerging procedure for intraventricular haemorrhage (IVH) and post-haemorrhagic ventricular dilatation (PHVD). However, there is considerable variation with regard to the indications, objectives, and surgical technique in NEL. There is currently no randomised trial evidence that supports the use of NEL in the context of PHVD. This study aims to form a consensus on technical variations in the indications and procedural steps of NEL. A mixed-methods modified Delphi consensus process was conducted between consultant paediatric neurosurgeons across the UK. Stages involved literature review, survey, focused online consultation, and iterative revisions until > 80% consensus was achieved. Twelve consultant paediatric neurosurgeons from 10 centres participated. A standardised protocol including indications, a 3-phase operative workflow (pre-ventricular, intraventricular, post-ventricular), and post-operative care was agreed upon by 100% of participants. Case- and surgeon-specific variation was considered and included through delineation of mandatory, optional, and not recommended steps. Expert consensus on a standardised protocol for NEL was achieved, delineating the surgical workflow into three phases such as pre-ventricular, intraventricular, and post-ventricular, each consisting of mandatory, optional, and not recommended steps. The work provides a platform for future trials, training, and implementation of NEL

Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017 : an analysis for the Global Burden of Disease Study 2017

Background Although the burden of influenza is often discussed in the context of historical pandemics and the threat of future pandemics, every year a substantial burden of lower respiratory tract infections (LRTIs) and other respiratory conditions (like chronic obstructive pulmonary disease) are attributable to seasonal influenza. The Global Burden of Disease Study (GBD) 2017 is a systematic scientific effort to quantify the health loss associated with a comprehensive set of diseases and disabilities. In this Article, we focus on LRTIs that can be attributed to influenza. Methods We modelled the LRTI incidence, hospitalisations, and mortality attributable to influenza for every country and selected subnational locations by age and year from 1990 to 2017 as part of GBD 2017. We used a counterfactual approach that first estimated the LRTI incidence, hospitalisations, and mortality and then attributed a fraction of those outcomes to influenza. Findings Influenza LRTI was responsible for an estimated 145 000 (95% uncertainty interval [UI] 99 000-200 000) deaths among all ages in 2017. The influenza LRTI mortality rate was highest among adults older than 70 years (16.4 deaths per 100 000 [95% UI 11.6-21.9]), and the highest rate among all ages was in eastern Europe (5.2 per 100 000 population [95% UI 3.5-7.2]). We estimated that influenza LRTIs accounted for 9 459 000 (95% UI 3 709 000-22 935 000) hospitalisations due to LRTIs and 81 536 000 hospital days (24 330 000-259 851 000). We estimated that 11.5% (95% UI 10.0-12.9) of LRTI episodes were attributable to influenza, corresponding to 54 481 000 (38 465 000-73 864 000) episodes and 8 172 000 severe episodes (5 000 000-13 296 000). Interpretation This comprehensive assessment of the burden of influenza LRTIs shows the substantial annual effect of influenza on global health. Although preparedness planning will be important for potential pandemics, health loss due to seasonal influenza LRTIs should not be overlooked, and vaccine use should be considered. Efforts to improve influenza prevention measures are needed. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe