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

Identification of Anthrax as the Cause of a Cluster of Unexplained Deaths, Uganda, 2023: The Role of Metagenomic Next-Generation Sequencing and Postmortem Specimens.

Between April and November 2023, 27 unexplained human deaths that presented with swelling of the arms, skin sores with black centers, difficulty in breathing, obstructed swallowing, headaches, and other body aches were reported in Kyotera District, Uganda by the Public Health Emergency Operations Center. Subsequently, the death of cattle on farms and the consumption of carcass meat by some residents were also reported. Field response teams collected clinical/epidemiological data and autopsy samples to determine the cause of deaths. Metagenomic next-generation sequencing (mNGS) and target enrichment sequencing conducted on postmortem samples confirmed Bacillus anthracis, the etiological agent of anthrax disease, as the cause of the deaths. Applying mNGS to autopsy specimens is useful as a retrospective tool for identifying high-consequence pathogens during suspected outbreaks of unknown etiology

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

Peer reviewe

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P &lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Validation of a cost-effective appendicectomy model for surgical training

Background Appendicitis is a commonly occurring condition worldwide. The gold standard treatment is appendicectomy. Although training models are commercially available for this procedure, they are often associated with high cost. Here we present a cost-effective model. Aim To establish construct validity of a cost-effective laparoscopic appendicectomy simulation model. Methods Three groups of surgeons were recruited; novices ( n = 31), of intermediate expertise ( n = 13) and experts ( n = 5) and asked to perform a simulated laparoscopic appendicectomy using the new model. Their performance was assessed by a faculty member and compared between the three groups using a validated scoring system (Global Operative Assessment of Laparoscopic Skills [GOALS] score). Results One-way ANOVA test showed a significant difference in task performance between groups ( p &lt; 0.0001). Post-hoc comparisons after the application of Bonferroni correction (statistically significant p value &lt;0.017) demonstrate a significant difference in performance between all groups for all GOALS categories as well as the total score. Effect size calculations showed that experience level had moderate (Eta-squared &gt;0.5 and &lt;0.8) and significant (&gt;0.8) impact on the performance of the simulated procedure. Conclusion The model described in this study is cost-effective, valid and can adequately simulate appendicectomy. The authors recommend inclusion of this model to postgraduate surgical training. </jats:sec

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