Percutaneous Coronary Interventions Using a Ridaforolimus-Eluting Stent in Patients at High Bleeding Risk.

BACKGROUND: Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug-eluting stents have been shown to be superior to bare-metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus-eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus-eluting stent in patients with HBR. METHODS AND RESULTS: This was a prospective, multicenter, binational, single-arm, open-label trial. Patients were defined as HBR according to the LEADERS-FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug-Coated Stent versus the Gazelle Bare-Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% (P<0.0001). Stent thrombosis (Academic Research Consortium definite and probable) occurred in 2 patients (0.6%). Bleeding Academic Research Consortium type 3 and 5 bleeding occurred in 6 patients (1.9%). CONCLUSIONS: We observed favorable results in patients with HBR who underwent percutaneous coronary intervention with a ridaforolimus-eluting stent and received shortened DAPT, including a low rate of ischemic events and low rate of stent thrombosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03877848

Association between operator volume and mortality in primary percutaneous coronary intervention

Background There is a paucity of real-world data assessing the association of operator volumes and mortality specific to primary percutaneous coronary intervention (PPCI). Methods Demographic, clinical and outcome data for all patients undergoing PPCI in Leeds General Infirmary, UK, between 1 January 2009 and 31 December 2011, and 1 January 2013 and 31 December 2013, were obtained prospectively. Operator volumes were analysed according to annual operator PPCI volume (low volume: 1–54 PPCI per year; intermediate volume: 55–109 PPCI per year; high volume: ≥110 PPCI per year). Cox proportional hazards regression analyses were undertaken to investigate 30-day and 12-month all-cause mortality, adjusting for confounding factors. Results During this period, 4056 patients underwent PPCI, 3703 (91.3%) of whom were followed up for a minimum of 12 months. PPCI by low-volume operators was associated with significantly higher adjusted 30-day mortality (HR 1.48 (95% CI 1.05 to 2.08); p=0.02) compared with PPCI performed by high-volume operators, with no significant difference in adjusted 12-month mortality (HR 1.26 (95% CI 0.96 to 1.65); p=0.09). Comparisons between low-volume and intermediate-volume operators, and between intermediate and high-volume operators, showed no significant differences in 30-day and 12-month mortality. Conclusions Low operator volume is independently associated with higher probability of 30-day mortality compared with high operator volume, suggesting a volume–outcome relationship in PPCI at a threshold higher than current recommendations

Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination - United States, 2001-2010

<p>Abstract</p> <p>Background</p> <p>Congenital rubella syndrome (CRS) is associated with several negative outcomes, including autism spectrum disorders (ASDs). The objective of this study was to estimate the numbers of CRS and ASD cases prevented by rubella vaccination in the United States from 2001 through 2010.</p> <p>Methods</p> <p>Prevention estimates were calculated through simple mathematical modeling, with values of model parameters determined from published literature. Model parameters included pre-vaccine era CRS incidence, vaccine era CRS incidence, the number of live births per year, and the percentage of CRS cases presenting with an ASD.</p> <p>Results</p> <p>Based on our estimates, 16,600 CRS cases (range: 8300-62,250) were prevented by rubella vaccination from 2001 through 2010 in the United States. An estimated 1228 ASD cases were prevented by rubella vaccination in the United States during this time period. Simulating a slight expansion in ASD diagnostic criteria in recent decades, we estimate that a minimum of 830 ASD cases and a maximum of 6225 ASD cases were prevented.</p> <p>Conclusions</p> <p>We estimate that rubella vaccination prevented substantial numbers of CRS and ASD cases in the United States from 2001 through 2010. These findings provide additional incentive to maintain high measles-mumps-rubella (MMR) vaccination coverage.</p

From Producer Innovation to User and Open Collaborative Innovation

In this paper we assess the economic viability of innovation by producers relative to two increasingly important alternative models: innovations by single user individuals or firms, and open collaborative innovation. We analyze the design costs and architectures and communication costs associated with each model. We conclude that both innovation by individual users and open collaborative innovation increasingly compete with and may displace producer innovation in many parts of the economy. We explain why this represents a paradigm shift with respect to innovation research, policymaking, and practice. We discuss important implications and offer suggestions for further research

Mapping Robots to Therapy and Educational Objectives for Children with Autism Spectrum Disorder

The aim of this study was to increase knowledge on therapy and educational objectives professionals work on with children with autism spectrum disorder (ASD) and to identify corresponding state of the art robots. Focus group sessions (n = 9) with ASD professionals (n = 53) from nine organisations were carried out to create an objectives overview, followed by a systematic literature study to identify state of the art robots matching these objectives. Professionals identified many ASD objectives (n = 74) in 9 different domains. State of the art robots addressed 24 of these objectives in 8 domains. Robots can potentially be applied to a large scope of objectives for children with ASD. This objectives overview functions as a base to guide development of robot interventions for these children

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication