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In this study, 37% of 146,000 PCR-tested contacts of infected persons in England were positive for SARS-CoV-2. Transmission of the alpha variant from twice-vaccinated index patients was rarer than that from unvaccinated index patients (adjusted rate ratio with BNT162b2, 0.32). Vaccine protection waned over time and was more effective against the alpha strain than against the delta strain.

AbstractObjectiveTo assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres.DesignObservational cohort study.SettingCommunity LFT pilot at covid-19 testing sites in Liverpool, UK.Participants5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020.InterventionsParticipants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites.Main outcome measuresSensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease.ResultsOf 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >106 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>104 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<104 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load.ConclusionsThe Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.

In partnership with NHS England, Genomics England’s ambitious plans to embed genomic medicine into routine patient care are well underway. Clare Turnbull and colleagues discuss its progress

Antibiotics underpin all of modern medicine, from routine major surgery through to caesarean sections and modern cancer therapies. These drugs have revolutionized how we practice medicine, but we are in a constant evolutionary battle to evade microbial resistance and this has become a major global public health problem. We have overused and misused these essential medicines both in the human and animal health sectors and this threatens the effectiveness of antimicrobials for future generations. We can only address the threat of antimicrobial resistance (AMR) through international collaboration across human and animal health sectors integrating social, economic and behavioural factors. Our global organizations are rising to the challenge with the recent World Health Assembly resolution on AMR and development of the Global Action plan but we must act now to avoid a return to a pre-antibiotic era.

[...]the need for increased education and awareness about antimicrobial resistance among the public, National Health Service managers, and health-care professionals. [...]the need to develop and improve surveillance systems for antimicrobial resistance and infectious diseases in general, particularly through improved linkage of data.

People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3–6 months after the second dose in the cancer cohort and control population. The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8–69·9) in the control population and 65·5% (65·1–65·9) in the cancer cohort. Vaccine effectiveness at 3–6 months was lower in the cancer cohort (47·0%, 46·3–47·6) than in the control population (61·4%, 61·4–61·5). COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

Background Self-sampling and self-testing have been increasingly used for sexually transmitted infections (STIs) and quickly became widespread during the COVID-19 pandemic. User acceptability, preferences, and experiences are important factors affecting self-sampling/self-testing uptake. Understanding these factors is key to managing infections and planning responses to health emergencies. This review aimed to identify user views and experiences related to the acceptability, usability, motivations and preferences for self-sampling/self-testing for infections. Methods We conducted a rapid systematic review. We searched Medline, EMBASE, PsycINFO, CINAHL, and Web of Science, limiting records to those published in English between 2014 and 2023. We also searched manually for additional peer-reviewed and grey literature. We included reports of public users’ views on self-sampling/self-testing for any symptomatic and asymptomatic infections (except human papillomavirus) with qualitative, mixed-methods or survey data relevant to the review aim. Data were extracted into tables and qualitative findings were coded in NVivo. We synthesised data narratively. Results We identified 194 eligible reports, including 64 from Europe (which we prioritised for detailed synthesis) and 130 from outside of Europe. In Europe, the studied infections were respiratory ( n  = 42, including 37 for COVID-19), STIs/HIV/genital infections ( n  = 20), and hepatitis C ( n  = 2). Findings indicate that users found self-sampling/self-testing acceptable across infection/sampling types, populations, settings, and countries. Users wanted self-sampling/self-testing to help determine infection status and protect others. The main benefits were privacy and convenience, helping reduce the potential stigma of STIs/HIV/genital infections, and (for COVID-19) informing behaviour (e.g., socialising, self-isolating) and contributing to research. Easier to perform and less invasive sampling approaches were more acceptable. However, some participants reported challenges to self-sampling/self-testing, such as not understanding instructions, pain/discomfort in collecting samples, and lack of confidence in interpreting results. Conclusions This review synthesised evidence on the acceptability of SS/ST and factors affecting it across different infections, sampling approaches, settings, and populations. Evidence shows that most people with experience of self-sampling/self-testing found it acceptable and were willing to accept some discomfort in favour of several perceived benefits. This amenability to self-sampling/self-testing could be leveraged for diagnosing infections and preventing transmission. It can be used to support the viability of new models of clinical care and pandemic preparedness. Trial registration The review was pre-registered on PROSPERO (ref. CRD42024507656 ).

The rising burden of chronic disease poses a challenge for all public health systems and requires innovative approaches to effectively improve population health. Persisting inequalities in health are of particular concern. Disadvantage because of education, income, or social position is associated with a larger burden of disease and, in particular, multimorbidity. Although much has been achieved to enhance population health, challenges remain, and approaches need to be revisited. In this paper, we join the debate about how a new wave of public health improvement might look. We start from the premise that population health improvement is conditional on a health-promoting societal context. It is characterised by a culture in which healthy behaviours are the norm, and in which the institutional, social, and physical environment support this mindset. Achievement of this ambition will require a positive, holistic, eclectic, and collaborative effort, involving a broad range of stakeholders. We emphasise three mechanisms: maximisation of the value of health and incentives for healthy behaviour; promotion of healthy choices as default; and minimisation of factors that create a culture and environment which promote unhealthy behaviour. We give examples of how these mechanisms might be achieved.

Mutational signatures are imprints of pathophysiological processes arising through tumorigenesis. We generated isogenic CRISPR-Cas9 knockouts (Δ) of 43 genes in human induced pluripotent stem cells, cultured them in the absence of added DNA damage, and performed whole-genome sequencing of 173 subclones. Δ Δ Δ Δ Δ Δ Δ Δ and Δ produced marked mutational signatures indicative of being critical mitigators of endogenous DNA modifications. Detailed analyses revealed mutational mechanistic insights, including how 8-oxo-dG elimination is sequence-context-specific while uracil clearance is sequence-context-independent. Mismatch repair (MMR) deficiency signatures are engendered by oxidative damage (C>A transversions), differential misincorporation by replicative polymerases (T>C and C>T transitions), and we propose a 'reverse template slippage' model for T>A transversions. Δ Δ and Δ signatures were similar to each other but distinct from Δ . Finally, we developed a classifier, MMRDetect, where application to 7,695 WGS cancers showed enhanced detection of MMR-deficient tumors, with implications for responsiveness to immunotherapies.