How can clinical research improve European health outcomes in cancer?

We review the mechanisms by which clinical cancer research can improve health outcomes and argue that this should be central to the development of policy. Recent series of major international studies have analysed large, often nationwide, datasets for cancer patient outcomes and participation in clinical research. They have evaluated and quantified the impact of new evidence generated by randomised controlled trials on cancer survival. They show a strong and probably causal relationship between the participation in clinical research in hospitals and the outcomes for patients with the disease under study in those hospitals. Also, institutions that are active in clinical trials appear to take up well evidenced innovations more rapidly than those which are not so engaged. Further work is necessary to confirm and examine the generalisability of these findings but we argue that all of these mechanisms are likely to lead to improved outcomes for patients as a consequence of the conduct of clinical research. The size of the benefit appears to be substantial and an active programme to promote clinical research across cancer care systems should be a part of National Cancer Plans and Cancer Control Strategies

Redeploying β-lactam antibiotics as a novel antivirulence strategy for the treatment of methicillin-resistant <i>Staphylococcus aureus</i> infections

Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. We report a new approach to the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections by demonstrating that oxacillin can be used to significantly attenuate the virulence of MRSA despite the pathogen being resistant to this drug. Using mechanistic in vitro assays and in vivo models of invasive pneumonia and sepsis, we show that oxacillin-treated MRSA strains are significantly attenuated in virulence. This effect is based primarily on the oxacillin-dependent repression of the accessory gene regulator quorum-sensing system and altered cell wall architecture, which in turn lead to increased susceptibility to host killing of MRSA. Our data indicate that beta-lactam antibiotics should be included in the treatment regimen as an adjunct antivirulence therapy for patients with MRSA infections. This would represent an important change to current clinical practice for treatment of MRSA infection, with the potential to significantly improve patient outcomes in a safe, cost-effective manner

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Redeploying β-lactam antibiotics as a novel antivirulence strategy for the treatment of methicillin-resistantstaphylococcus aureusinfections

Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. We report a new approach to the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections by demonstrating that oxacillin can be used to significantly attenuate the virulence of MRSA despite the pathogen being resistant to this drug. Using mechanistic in vitro assays and in vivo models of invasive pneumonia and sepsis, we show that oxacillin-treated MRSA strains are significantly attenuated in virulence. This effect is based primarily on the oxacillin-dependent repression of the accessory gene regulator quorum-sensing system and altered cell wall architecture, which in turn lead to increased susceptibility to host killing of MRSA. Our data indicate that beta-lactam antibiotics should be included in the treatment regimen as an adjunct antivirulence therapy for patients with MRSA infections. This would represent an important change to current clinical practice for treatment of MRSA infection, with the potential to significantly improve patient outcomes in a safe, cost-effective manner

Celebrating 50 years of ACAL: Selected papers from the 50th Annual Conference on African Linguistics

The papers in this volume were presented at the 50th Annual Conference on African Linguistics held at the University of British Columbia in 2019. The contributions span a range of theoretical topics as well as topics in descriptive and applied linguistics. The papers reflect the typological and genetic diversity of languages in Africa and also represent the breadth of the ACAL community, with papers from both students and more senior scholars, based in North America and beyond. They thus provide a snapshot on current research in African linguistics, from multiple perspectives. To mark the 50th anniversary of the conference, the volume editors reminisce, in the introductory chapter, about their memorable ACALs

Celebrating 50 years of ACAL: Selected papers from the 50th Annual Conference on African Linguistics

The papers in this volume were presented at the 50th Annual Conference on African Linguistics held at the University of British Columbia in 2019. The contributions span a range of theoretical topics as well as topics in descriptive and applied linguistics. The papers reflect the typological and genetic diversity of languages in Africa and also represent the breadth of the ACAL community, with papers from both students and more senior scholars, based in North America and beyond. They thus provide a snapshot on current research in African linguistics, from multiple perspectives. To mark the 50th anniversary of the conference, the volume editors reminisce, in the introductory chapter, about their memorable ACALs

Web Analysis and Design - Project Planning

This reading material forms part of the "Project Planning" topic in the Web Analysis and Design module

Celebrating 50 years of ACAL: Selected papers from the 50th Annual Conference on African Linguistics

The papers in this volume were presented at the 50th Annual Conference on African Linguistics held at the University of British Columbia in 2019. The contributions span a range of theoretical topics as well as topics in descriptive and applied linguistics. The papers reflect the typological and genetic diversity of languages in Africa and also represent the breadth of the ACAL community, with papers from both students and more senior scholars, based in North America and beyond. They thus provide a snapshot on current research in African linguistics, from multiple perspectives. To mark the 50th anniversary of the conference, the volume editors reminisce, in the introductory chapter, about their memorable ACALs