Phenotypic and genotypic characteristics of small colony variants and their role in chronic infection

Small colony variant (SCV) bacteria arise spontaneously within apparently homogeneous microbial populations, largely in response to environmental stresses, such as antimicrobial treatment. They display unique phenotypic characteristics conferred in part by heritable genetic changes. Characteristically slow growing, SCVs comprise a minor proportion of the population from which they arise but persist by virtue of their inherent resilience and host adaptability. Consequently, SCVs are problematic in chronic infection, where antimicrobial treatment is administered during the acute phase of infection but fails to eradicate SCVs, which remain within the host causing recurrent or chronic infection. This review discusses some of the phenotypic and genotypic changes that enable SCVs to successfully proliferate within the host environment as potential pathogens and strategies that could ameliorate the resolution of infection where SCVs are present

Does practice analysis agree with the ambulatory care sensitive conditions list of avoidable unplanned admissions: cross-sectional study in the East of England.

Objectives: To use Significant Event Audits (SEA) in primary care to determine which of a sample of emergency (unplanned) admissions were potentially avoidable; and compare to the NHS list of ambulatory care sensitive conditions (ACSCs). Design: Analysis of unplanned medical admissions randomly identified in secondary care. Setting: Primary Care in the East of England. Participants: 20 general practice teams trained to use SEA on unplanned admissions to identify potentially preventable factors. Interventions: SEA of admissions. Main outcome measures: Level of agreement between those admissions identified as potentially preventable by SEA and the NHS ACSC list. Results: 132 (26%) of randomly selected patients with unplanned admissions gave consent and an SEA was performed by their primary practice team. 130 SEA reports had sufficient data for our analysis. Practices concluded that 17 (13%) of admissions were potentially preventable. The NHS ACSC list identified 36 admissions (28%) as potentially preventable. There was a low level of agreement between the practices and the NHS list as to which admissions were preventable (Kappa = 0.253). The ACSC list consisted mainly of respiratory admissions whereas the practice list identified a wider range of cases and identified context-specific factors as important. Conclusions: There was disagreement between the NHS list and practice conclusions of potentially avoidable admissions. The SEAs suggest that the pathway into unplanned admission may be less dependent on the condition than on context-specific factors, and the assumption that unplanned admissions for ACSC conditions are reasonable indicators of performance for primary care may not be valid

Does practice analysis agree with the ambulatory care sensitive conditions’ list of avoidable unplanned admissions?:a cross-sectional study in the East of England

Objectives To use significant event audits (SEAs) in primary care to determine which of a sample of emergency (unplanned) admissions were potentially avoidable; and compare with the National Health Service (NHS) list of ambulatory care sensitive conditions (ACSCs).Design Analysis of unplanned medical admissions randomly identified in secondary care.Setting Primary care in the East of England.Participants 20 general practice teams trained to use SEA on unplanned admissions to identify potentially preventable factors.Interventions SEA of admissions.Main outcome measures Level of agreement between those admissions identified as potentially preventable by SEA and the NHS ACSC list.Results 132 (26%) of randomly selected patients with unplanned admissions gave consent and an SEA was performed by their primary practice team. 130 SEA reports had sufficient data for our analysis. Practices concluded that 17 (13%) admissions were potentially preventable. The NHS ACSC list identified 36 admissions (28%) as potentially preventable. There was a low level of agreement between the practices and the NHS list as to which admissions were preventable (kappa=0.253). The ACSC list consisted mainly of respiratory admissions whereas the practice list identified a wider range of cases and identified context-specific factors as important.Conclusions There was disagreement between the NHS list and practice conclusions of potentially avoidable admissions. The SEAs suggest that the pathway into unplanned admission may be less dependent on the condition than on context-specific factors, and the assumption that unplanned admissions for ACSCs are reasonable indicators of performance for primary care may not be valid

Do You Need to Travel? Mapping Face-to-Face Communication Objectives to Technology Affordances

Computer-mediated communications (CMC) can be used as a substitute for face-to-face (FtF) meetings but their effectiveness is highly context dependent. This paper describes a theoretical framework and initial experimental design for characterizing a travel replacement threshold. This effort begins with a use case of remote engineering maintenance training, conducted in three conditions: side-by-side (physically proximate), teleconference (using off-the-shelf software), and a custom VR/AR system designed to provide the apprentice with a virtual view of both the instructor’s larger scale lab and smaller scale workbench. The research hypotheses, experimental protocol, and dependent measures are described. The task involves an instructor demonstrating a circuit board troubleshooting task to a remote apprentice. The apprentice then completes the trained task independently, and performance and subject preferences are compared across conditions. The details of this paper, the result of extensive literature review and winnowing of variables, may assist researchers exploring CMC, training, or social communication

Virology under the microscope—a call for rational discourse

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Which types of emergency medical admissions may be preventable? Analyses of 132 randomly selected cases

Problem In 2012-13, there were 5.3 million emergency admissions to hospitals, an increase of 47% over the last 15 years, costing approximately £12.5 billion and occupying 67% of hospital beds. In an attempt to reduce these admissions, lists of potentially avoidable admissions (termed ACSCs) have been developed based on consensus opinions of expert physician panels drawn from secondary and primary care, examining diagnostic disease codes. We aimed to compare this list of ACSCs used in the NHS with the conclusions of GP practice teams using significant event analysis (SEA) on emergency admissions. Approach We performed a study in 20 practices in East Anglia. We trained each practice to carry out SEAs in a systematic way. Hospitals randomly selected emergency admissions (one per week per practice) and practices approached patients for consent. The practice used SEA to examine (1) details of what happened before the admission (2) the people and systems that were involved (3) what might have been done differently to avoid the admission and (4) develop specific action points to promote change in practice that might help reduce future unplanned admissions. The practice reached a consensus as to whether the admission contained avoidable factors. The ICD 10 disease code for the primary cause of admission was used to identify ACSCs. An inter-rater reliability analysis using the Cohen Kappa statistic was performed to determine consistency between the lists of potentially avoidable admissions determined using SEA with those identified by the ACSC list. Findings SEAs were carried out on 26% of selected admissions (132 cases). Practice teams identified 13% (17) of cases as potentially avoidable, and the ACSC list categorised 28 % (36) as potentially avoidable. The inter-rater reliability was found to be Kappa = 0.253 (p=0.001), which represents only fair agreement. The ACSC list mainly comprised of respiratory admissions, Pneumonia 14 cases (39%), COPD 7 (19%), Asthma 3 (8%) and Bronchiectasis 1 (3%). Practice teams identified fewer respiratory cases as potentially avoidable, Pneumonia 4 (24%), Asthma 1 (6%), COPD 1 (6%), and Bronchiectasis 1 (6%). Practices identified a wider range of cases including admission with constipation, anxiety, cancer and intracranial haemorrhage. Consequences There was only a fair level of agreement on which admissions might be avoidable when comparing the ACSC list used by the NHS with the list generated by the practice team using SEA. It is plausible that case-based analysis of actual admissions may be more sensitive in detecting factors that might be associated with an avoidable admission than simple diagnostic labels. We propose further work is done using a case-based approach to review the ACSC list and to produce an updated list of conditions and factors (practitioner, patient and systems) which might identify potentially avoidable admissions