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Background: Single-occupancy isolation rooms are a finite resource in UK hospitals but are crucial in preventing transmission of infection. Patients with suspected gastroenteritis are nursed in single-occupancy rooms, but delays in laboratory testing lead to non-infectious patients remaining isolated for prolonged periods unnecessarily. Rapid molecular test panels for gastrointestinal pathogens have a run time of around 1 h but their clinical impact is unknown. We aimed to evaluate the clinical impact of syndromic molecular point-of-care testing (mPOCT) for gastrointestinal pathogens in adult patients presenting to hospital with suspected gastroenteritis on single-occupancy room use and a range of other outcome measures., Methods: In this pragmatic, open-label, randomised controlled trial, we enrolled adults hospitalised with suspected gastroenteritis in a large UK hospital. Patients were randomly allocated (1:1) to receive syndromic mPOCT of stool or rectal samples, or to routine clinical care (control) with laboratory testing. The primary outcome was the duration of time in single-occupancy rooms assessed on a modified intention-to-treat basis. Secondary outcomes included the time to results, time to de-isolation, antibiotic use, and safety outcomes. The study was registered with ISRCTN, ISRCTN88918395, and is complete., Findings: Between March 20, 2017 and March 17, 2020, from 455 patients assessed for eligibility, we enrolled 278 patients, 138 assigned to mPOCT (one withdrawal) and 140 to the control group. The duration (geometric mean) of single-occupancy room isolation was 1·8 days (95% CI 1·5-2·2) in the mPOCT group compared with 2·6 days (2·2-3·0) in the control group (exponentiated coefficient 0·70 [95% CI 0·56 to 0·87]; p=0·0017). The median (IQR) time to results was 1·7 h (1·5-2·0) for mPOCT and 44·7 h (21·2-66·1) for the control group (p<0·0001). Time to de-isolation was 0·6 days (0·3-1·8) in the mPOCT group compared with 2·2 days (1·2-3·2) in the control group, (p<0·0001). Antibiotics were given in 89 (65%) of 137 in the mPOCT group and 66 (47%) of 140 in the control group (p=0·0028). There were no differences between groups in length of hospital stay, or in safety outcomes including mortality, intensive care unit admission, or readmission to hospital., Interpretation: mPOCT for gastrointestinal pathogens in patients with suspected gastroenteritis returned results more rapidly than conventional testing and was associated with a reduction in single-occupancy room use. However, these benefits need to be balanced against a potential increase in antibiotic use., Funding: University Hospital Southampton NHS Foundation Trust., Competing Interests: Declaration of interests TWC has received speaker fees, honoraria, travel reimbursement, and equipment and consumables at discount or free of charge for purposes independent of research, outside of this submitted study, from BioFire Diagnostics–bioMérieux and QIAGEN. He has received consultancy fees from BioFire Diagnostics–bioMérieux, Cepheid, Roche, Janssen, Synairgen, Randox Laboratories, IP Pragmatics, and Cidara therapeutics; has received speaker fees or honoraria from Janssen, Sanofi, and Medscape; has received honoraria for participation in advisory boards from Cepheid, Roche, Janssen, Seqirus, Sanofi, and Shionogi; is a member of an independent data monitoring committee for a trial sponsored by Roche; owns Synairgen stock; has acted as the UK chief investigator for a study sponsored by Janssen; was supported by a National Institute for Health Research (NIHR) post-doctoral fellowship (grant number PDF 2016-09-061); has received grant funding via an NIHR AMR research infrastructure award; andhas received grant funding from the Norwegian Research Council for the CAPNOR randomised controlled trial. NJB is supported by the NIHR Clinical Lecturer programme. KRB is supported by the NIHR Academic Clinical Fellow programme. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Addictive behavior sometimes involves harmful moral transgressions for which the addicted individual may be blamed. However, blame may motivate addiction stigma, which has its own harmful consequences, including failures to provide or seek out treatment and recovery resources. Minimizing blame and stigma, while acknowledging the moral dimension of addictive behavior, thus recommends itself as a worthy public health objective. The disease and choice models of addiction both face difficulties in reducing stigma, the latter because harmful choices are considered culpable. By challenging the widely held libertarian conception of human agency, an explicitly deterministic understanding of the genesis and expression of addiction, including voluntary choices, can help keep reactive attitudes to wrongdoing in check. This will mitigate the perceived blameworthiness of addicted individuals, thus reducing stigma and increasing the chances of finding compassionate and effective care. Such an approach to addiction will recognize the need for moral accountability but not include punitive attitudes and policies justified by belief in libertarian agency., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Effective antigen-sparing vaccines are needed to confront pandemic influenza. Whole-virion and oil-in-water adjuvanted vaccines are the most effective formulations against H5N1 avian influenza. We assessed the safety and immunogenicity in adults in the UK of pandemic H1N1 whole-virion vaccine and oil-in-water adjuvanted vaccine purchased by the UK government in 2009., Methods: In our randomised, observer-blind, parallel-group, controlled trial, healthy adults aged 18-44 years, 45-64 years, and 65 years and older (from Oct 19, to Nov 12, 2009) received two doses of vaccine given 21 days apart: either 7·5 μg of haemagglutinin formulated as whole-virion vaccine, or 3·75 μg of haemagglutinin formulated as split-virion vaccine with AS03(A) oil-in-water adjuvant. Assignment was by a computer-generated code, with random permuted blocks of two, four, and six. All participants and investigators were unaware of vaccine assignments. The trial was done at three hospitals in the UK. We measured antibody titres with a haemagglutination-inhibition assay at baseline; 7, 14, and 21 days after each vaccination; and at 6 months after the first dose. Primary outcome was vaccine immunogenicity of the full analysis set by the EU Committee of Human Medicinal Products licensing criteria. This study is registered with ISRCTN, number ISRCTN92328241., Findings: At day 0, baseline antibody (titre ≥1/8) was detected in 44 (13%) of 347 participants. Sera from 95% to 98% of participants were assessed for immunogenicity on days 7, 14, 21, 28, 35, and 42, and at 6 months. On day 21 after one dose of adjuvanted AS03(A) or whole-virion vaccine, 63 (94%, 95 CI 85·4-98·4) of 67 and 50 (71%, 59·4-81·6) of 70 participants aged 18-44 years, 51 (77%, 65·3-86·7) of 66 and 26 (39%, 27·1-51·5) of 67 aged 45-64 years, and 19 (51%, 34·4-68·1) of 37 and 11 (32%, 17·4-50·5) of 34 aged 65 years or older had titres of 1:40 or greater. On day 42 (21 days after the second dose), 64 (100%, 94·4-100) of 64 and 49 (73%, 60·9-83·2) of 67 participants aged 18-44 years, 59 (91%, 81·0-96·5) of 65 and 29 (43·9%, 31·7-56·7) of 66 aged 45-64 years, and 28 (76%, 58·8-88·2) of 37 and 12 (36%, 20·4-54·9) of 33 aged 65 years or older had titres of 1/40 or greater. At 6 months, 62 (98%, 91·5-100) of 63 and 54 (78%, 66·7-87·3) of 69 participants aged 18-44 years, 54 (82%, 70·4-90·2) of 66 and 37 (55%, 42·6-67·4) of 67 aged 45-64 years, and 21 (57%, 39·5-72·9) of 37 and 10 (29%, 15·1-47·5) of 34 aged 65 years or older had titres of 1/40 or greater. There were no vaccine-related serious adverse events. Whole-virion vaccine was associated with fewer local and systemic reactions than adjuvanted vaccine., Interpretation: AS03(A)-adjuvanted vaccine was more immunogenic against pandemic influenza A H1N1 virus than whole-virion vaccine and offers greater antigen-sparing capacity. A two-dose strategy should be considered for older people., Funding: Department of Health, National Institute for Health Research Evaluation, Trials and Studies Coordinating Centre., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Specific anti-influenza drugs are available for the management of seasonal influenza., Objectives: To evaluate European recommendations and guidelines for the use of antiviral drugs in treatment and prevention of seasonal influenza., Design: Guidelines issued between January 2003 and September 2007 were scored using the AGREE appraisal instrument and evaluated., Results: Guidelines were obtained from France, Germany, Italy, Netherlands, Poland, Portugal, Sweden and the UK. Most guidelines recommend neuraminidase inhibitors over M2 inhibitors, but three countries were unclear or suggested M2 inhibitor use in some circumstances. Clinical diagnosis of patients eligible for treatment during periods of influenza activity is acceptable except in Poland where virological confirmation is required. Guidelines recommend antiviral use in patients at high risk of complications, except in Germany where there is a strong recommendation to treat all patients. Post-exposure prophylaxis for household contacts is recommended in Sweden and Germany, but not other countries. Only UK guidelines are regularly updated. All scored fairly poorly by the AGREE instrument. French, Polish, Swedish and UK guidelines were recommended., Conclusion: Major variations exist in recommendations for treatment and prevention of seasonal influenza. Development of Pan-European guidance should be considered. Updating is important to reflect emerging patterns of antiviral resistance.