A survey of minimally invasive cardiac surgery during the COVID-19 pandemic

BACKGROUND: Lack of scientific data on the feasibility and safety of minimally invasive cardiac surgery (MICS) during the COVID-19 pandemic has made clinical decision making challenging. This survey aimed to appraise MICS activity in UK cardiac units and establish a consensus amongst front-line MICS surgeons regarding standard best MICS practise during the pandemic. METHODS: An online questionnaire was designed through the ‘googleforms’ platform. Responses were received from 24 out of 28 surgeons approached (85.7%), across 17 cardiac units. RESULTS: There was a strong consensus against a higher risk of conversion from minimally invasive to full sternotomy (92%; n = 22) nor there is increased infection (79%; n = 19) or bleeding (96%; n = 23) with MICS compared to full sternotomy during the pandemic. The majority of respondents (67%; n = 16) felt that it was safe to perform MICS during COVID-19, and that it should not be halted (71%; n = 17). London cardiac units experienced a decrease in MICS (60%; n = 6), whereas non-London units saw no reduction. All London MICS surgeons wore an FP3 mask compared to 62% (n = 8) of non-London MICS surgeons, 23% (n = 3) of which only wore a surgical mask. London MICS surgeons felt that routine double gloving should be done (60%; n = 6) whereas non-London MICS surgeons held a strong consensus that it should not (92%; n = 12). CONCLUSION: Whilst more robust evidence on the effect of COVID-19 on MICS is awaited, this survey provides interesting insights for clinical decision-making regarding MICS and aids to facilitate the development of standardised MICS guidelines for an effective response during future pandemics

Machine learning for real-time aggregated prediction of hospital admission for emergency patients

Machine learning for hospital operations is under-studied. We present a prediction pipeline that uses live electronic health-records for patients in a UK teaching hospital's emergency department (ED) to generate short-term, probabilistic forecasts of emergency admissions. A set of XGBoost classifiers applied to 109,465 ED visits yielded AUROCs from 0.82 to 0.90 depending on elapsed visit-time at the point of prediction. Patient-level probabilities of admission were aggregated to forecast the number of admissions among current ED patients and, incorporating patients yet to arrive, total emergency admissions within specified time-windows. The pipeline gave a mean absolute error (MAE) of 4.0 admissions (mean percentage error of 17%) versus 6.5 (32%) for a benchmark metric. Models developed with 104,504 later visits during the Covid-19 pandemic gave AUROCs of 0.68-0.90 and MAE of 4.2 (30%) versus a 4.9 (33%) benchmark. We discuss how we surmounted challenges of designing and implementing models for real-time use, including temporal framing, data preparation, and changing operational conditions

A Critical Review of Adverse Effects to the Kidney: Mechanisms, Data Sources and In Silico Tools to Assist Prediction

Introduction: The kidney is a major target for toxicity elicited by pharmaceuticals and environmental pollutants. Standard testing which often does not investigate underlying mechanisms has proven not to be an adequate hazard assessment approach. As such, there is an opportunity for the application of computational approaches that utilise multi-scale data based on the Adverse Outcome Pathway (AOP) paradigm, coupled with an understanding of the chemistry underpinning the molecular initiating event (MIE) to provide a deep understanding of how structural fragments of molecules relate to specific mechanisms of nephrotoxicity. Aims covered: The aim of this investigation was to review the current scientific landscape related to computational methods, including mechanistic data, AOPs, publicly available knowledge bases and current in silico models, for the assessment of pharmaceuticals and other chemicals with regard to their potential to elicit nephrotoxicity. A list of over 250 nephrotoxicants enriched with, where possible, mechanistic and AOP-derived understanding was compiled. Expert opinion: Whilst little mechanistic evidence has been translated into AOPs, this review identified a number of data sources of in vitro, in vivo and human data that may assist in the development of in silico models which in turn may shed light on the inter-relationships between nephrotoxicity mechanisms

The Emergence and Development of Association Football: Influential Sociocultural Factors in Victorian Birmingham

This article explores the interdependent, complex sociocultural factors that facilitated the emergence and diffusion of football in Birmingham. The focus is the development of football in the city, against the backdrop of the numerous social changes in Victorian Birmingham. The aim is to fill a gap in the existing literature which seemingly overlooked Birmingham as a significant footballing centre, and the ‘ordinary and everyday’ aspects of the game’s early progression. Among other aspects, particular heed is paid to the working classes’ involvement in football, as previous literature has often focused on the middle classes and their influence on and participation in organized sport. As the agency of the working classes along with their mass participation and central role in the game’s development is unfolded, it is argued that far from being passive cultural beings, the working classes, from the beginnings, actively negotiated the development of their own emergent football culture

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

Developing a framework for assessing respiratory sensitization: A workshop report

Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, –omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment

The Mass of KOI-94d and a Relation for Planet Radius, Mass, and Incident Flux

We measure the mass of a modestly irradiated giant planet, KOI-94d. We wish to determine whether this planet, which is in a 22 day orbit and receives 2700 times as much incident flux as Jupiter, is as dense as Jupiter or rarefied like inflated hot Jupiters. KOI-94 also hosts at least three smaller transiting planets, all of which were detected by the Kepler mission. With 26 radial velocities of KOI-94 from the W. M. Keck Observatory and a simultaneous fit to the Kepler light curve, we measure the mass of the giant planet and determine that it is not inflated. Support for the planetary interpretation of the other three candidates comes from gravitational interactions through transit timing variations, the statistical robustness of multi-planet systems against false positives, and several lines of evidence that no other star resides within the photometric aperture. We report the properties of KOI-94b (M_P = 10.5 ± 4.6 M_⊕, R_P = 1.71 ± 0.16 R_⊕, P = 3.74 days), KOI-94c (M_P = 15.6^(+5.7)_(-15.6) M_⊕, R_P = 4.32 ± 0.41 R_⊕, P = 10.4 days), KOI-94d (M_P = 106 ± 11 M_⊕, R_P = 11.27 ± 1.06 R_⊕, P = 22.3 days), and KOI-94e (M_P = 35^(+18)_(-28) M_⊕, R_P = 6.56 ± 0.62 R_⊕, P = 54.3 days). The radial velocity analyses of KOI-94b and KOI-94e offer marginal (>2σ) mass detections, whereas the observations of KOI-94c offer only an upper limit to its mass. Using the KOI-94 system and other planets with published values for both mass and radius (138 exoplanets total, including 35 with M_P 150 M_⊕. These equations can be used to predict the radius or mass of a planet

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