Publications by authors named "Martin Llewelyn"

Objectives: In 2017, the WHO introduced the AWaRe (ccess, tch and serve) classification of antibiotics to support antibiotic stewardship (AMS) at local, national and global levels. We assessed the categorization of each of the antibiotics for systemic use for antimicrobial stewardship and quality improvement practice across primary and secondary care in the UK, proposing a nationally adapted UK-AWaRe classification.

Methods: A four-stage modified Delphi survey was conducted to review the AWaRe classifications in light of antibiotic resistance profiles, antibiotic use and stewardship practice in the UK.

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Background: Heterologous schedules of booster vaccines for COVID-19 following initial doses of mRNA or adenoviral vector vaccines have been shown to be safe and immunogenic. There are few data on booster doses following initial doses of protein nanoparticle vaccines.

Methods: Participants of the phase 3 clinical trial of the COVID-19 vaccine NVX-CoV2373 (EudraCT 2020-004123-16) enroled between September 28 and November 28, 2020, who received 2 doses of NVX-CoV2373 administered 21 days apart were invited to receive a third dose booster vaccine of BNT162b2 (wild type mRNA vaccine) as a sub-study of the COV-BOOST clinical trial, and were followed up for assessment of safety, reactogenicity and immunogenicity to day 242 post-booster.

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Aim: To integrate the quantitative and qualitative data collected as part of the PEACH (Procalcitonin: Evaluation of Antibiotic use in COVID-19 Hospitalised patients) study, which evaluated whether procalcitonin (PCT) testing should be used to guide antibiotic prescribing and safely reduce antibiotic use among patients admitted to acute UK National Health Service (NHS) hospitals.

Design: Triangulation to integrate quantitative and qualitative data.

Setting And Participants: Four data sources in 148 NHS hospitals in England and Wales including data from 6089 patients.

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Objective: Skin temperature assessment is essential for the diagnosis of cellulitis and monitoring treatment response, but is currently subjective and can contribute to overdiagnosis. We aimed to characterise skin temperature changes over time in cellulitis and compare two objective measurement approaches, a thermal imaging camera (TIC) and a non-contact infrared thermometer (NCIT).

Design: A device comparison study nested within a prospective cohort.

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Background: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use.

Methods And Findings: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention.

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Background: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK.

Objectives: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic.

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Article Synopsis
  • - A study evaluated the cost-effectiveness of using procalcitonin (PCT) testing to guide antibiotic decisions for COVID-19 patients in UK hospitals during the pandemic.
  • - Data from 11 NHS hospitals showed those tested with PCT had shorter hospital stays, reduced antibiotic use, and better quality-adjusted life years (QALYs) compared to those who were not tested.
  • - Results suggest that PCT testing is likely to be cost-effective for hospitalized COVID-19 patients, although there is some uncertainty regarding these findings.
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Background: Information on the quality of life of people hospitalised with COVID-19 is important, both in assessing the burden of disease and the cost-effectiveness of treatments. However, there were potential barriers to collecting such evidence.

Objective: To review the existing evidence on quality of life for people hospitalised with COVID-19, with a focus on the amount of evidence available and methods used.

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Objectives: To identify patterns in inflammatory marker and vital sign responses in adult with suspected bloodstream infection (BSI) and define expected trends in normal recovery.

Methods: We included patients ≥16 y from Oxford University Hospitals with a blood culture taken between 1-January-2016 and 28-June-2021. We used linear and latent class mixed models to estimate trajectories in C-reactive protein (CRP), white blood count, heart rate, respiratory rate and temperature and identify CRP response subgroups.

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Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid).

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Multi-drug-resistant infection is a significant public health risk. Rapidly detecting and antimicrobial-resistant (AMR) determinants by metagenomic sequencing of urine is possible, although high levels of host DNA and overgrowth of contaminating species hamper sequencing and limit genome coverage. We performed Nanopore sequencing of nucleic acid amplification test-positive urine samples and culture-positive urethral swabs with and without probe-based target enrichment, using a custom SureSelect panel, to investigate whether selective enrichment of DNA improves detection of both species and AMR determinants.

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Objectives: Cellulitis is often treated with antibiotics for longer than recommended by guidelines. Prolonged therapy may reduce recurrence in certain patients, but it is not known which patients are at greatest risk. Our objective was to develop and temporally validate a risk prediction score to identify patients attending hospital with cellulitis at highest risk of recurrence.

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Article Synopsis
  • - The study aimed to understand the factors influencing antibiotic prescribing decisions for COVID-19 pneumonia patients during the initial pandemic phase, using interviews with clinicians across NHS trusts in England and Wales.
  • - Clinicians' antibiotic prescriptions were initially guided by fears of secondary bacterial infections, but as their experience with COVID-19 grew, they became more adept at identifying when antibiotics were necessary versus when they weren't.
  • - A model was created to illustrate the decision-making process, emphasizing the roles of clinician confidence, experience, senior support, and organizational context in improving antibiotic stewardship during the pandemic.
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Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies.

Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors.

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Background: Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection.

Methods: A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using 'pancreatic stone protein', 'PSP', 'regenerative protein', 'lithostatin' combined with 'infection' and 'sepsis' found 46 records.

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Background: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease.

Objectives: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors.

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Background: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave.

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Antimicrobial resistance (AMR) is a threat to global public health. However, unsatisfactory approaches to directly measuring the AMR burden carried by individuals has hampered efforts to assess interventions aimed at reducing selection for AMR. Metagenomics can provide accurate detection and quantification of AMR genes within an individual person's faecal flora (their gut "resistome").

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Article Synopsis
  • Urinary tract infections (UTIs) are common, especially in women, and current tests to diagnose them aren't always very accurate.
  • Researchers looked at new biomarkers in urine that might help doctors tell if someone has a UTI or just harmless bacteria.
  • They found some promising biomarkers like IL-6 and IL-8, but more studies are needed to see if they really work for diagnosing UTIs before they can be used in hospitals.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health.

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In its first 2 decades, the NHS witnessed the near eradication of life-threatening community-acquired infections. However, medical advances have created different challenges (such as antimicrobial resistance and healthcare-associated infections) against a background of an increasingly ageing population. The recent COVID-19 pandemic has highlighted a lack of parity with regards to provision of NHS 'infection services' (infectious diseases, microbiology and virology) across the UK, which urgently needs to be addressed.

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Infection expertise in the NHS has historically been provided predominantly by hospital-based medical microbiologists responsible for provision of diagnostic services and advice to front-line clinicians. While most hospitals had consultant-led microbiology departments, infectious iiseases departments were based in a small number of specialist centres. The demand for infection expertise is growing in the NHS, driven by advances in medical care, increasing awareness of the impact of antibiotic resistant and healthcare associated infections and threats from emerging infectious diseases.

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Objectives: To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort.

Methods: Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S.

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Article Synopsis
  • A study was conducted to assess a comprehensive behavior change intervention aimed at reducing unnecessary antibiotic use in hospitals by encouraging prescribers to make appropriate decisions during clinical reviews.
  • The research utilized a randomized controlled trial across multiple hospitals in the UK, tracking outcomes such as antibiotic dosage and patient mortality within 30 days post-admission through electronic health records and audits.
  • The effectiveness of the intervention was analyzed using time series methods and random-effects meta-analysis, with the study now completed and registered for validation.
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