Undertaking clinical audit, with reference to a Prescribing Observatory for Mental Health audit of lithium monitoring

Audit is an important tool for quality improvement. The collection of data on clinical performance against evidence-based and clinically relevant standards, which are considered by clinicians to be realistic in routine practice, can usefully prompt reflective practice and the implementation of change. Evidence of participation in clinical audit is required to achieve intended learning outcomes for trainees in psychiatry and revalidation for those who are members of the Royal College of Psychiatrists. This article addresses some of the practical steps involved in conducting an audit project, and, to illustrate key points, draws on lessons learnt from a national, audit-based, quality improvement programme of lithium prescribing and monitoring conducted through the Prescribing Observatory for Mental Health

The impact of pneumolysin on the macrophage response to Streptococcus pneumoniae is strain-dependent

Streptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306). However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467) to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2), p19 subunit of IL-23 (IL23A) and IFNβ (IFNB1) compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism

Isolation site influences virulence phenotype of serotype 14 Streptococcus pneumoniae strains belonging to multilocus sequence type 15

Streptococcus pneumoniae is a diverse species causing invasive as well as localized infections that result in massive global morbidity and mortality. Strains vary markedly in pathogenic potential, but the molecular basis is obscured by the diversity and plasticity of the pneumococcal genome. We have previously reported that S. pneumoniae serotype 3 isolates belonging to the same multilocus sequence type (MLST) differed markedly in in vitro and in vivo phenotypes, in accordance with the clinical site of isolation, suggesting stable niche adaptation within a clonal lineage. In the present study, we have extended our analysis to serotype 14 clinical isolates from cases of sepsis or otitis media that belong to the same MLST (ST15). In a murine intranasal challenge model, five ST15 isolates (three from blood and two from ears) colonized the nasopharynx to similar extents. However, blood and ear isolates exhibited significant differences in bacterial loads in other host niches (lungs, ear, and brain) at both 24 and 72 h postchallenge. In spite of these differences, blood and ear isolates were present in the lungs at similar levels at 6 h postchallenge, suggesting that early immune responses may underpin the distinct virulence phenotypes. Transcriptional analysis of lung tissue from mice infected for 6 h with blood isolates versus ear isolates revealed 8 differentially expressed genes. Two of these were exclusively expressed in response to infection with the ear isolate. These results suggest a link between the differential capacities to elicit early innate immune responses and the distinct virulence phenotypes of clonally related S. pneumoniae strains

Operations management in high value manufacturing

This paper explores the issue of high value manufacturing from an operations management perspective and discusses the critical role that the operations management community must play in moving manufacturing organisations to 'higher value ground'. An exploratory study was carried out in two phases. In Phase 1 existing literature was examined following a systematic review process. This was followed by a stakeholder analysis that included manufacturing companies, government agencies and consultancies and case studies of three organisations that had recently repositioned their businesses. Phase 2 comprised of a focus group based industry consultation exercise. The aim of the second phase was to validate and refine the findings from the initial phase and to generate the key ideas that would inform a future research agenda. This paper provides the foundation for further research by identifying those operational issues that are affecting industry as it seeks to move to higher value ground

Insouciance and inexperience: A deadly combination when dealing with COVID-19.

This article gives key reasons for the UK's tardy and confused attempts to react to the COVID-19 pandemic. It explains very poor outcomes in the UK (in terms of the spread of the virus and high mortality, already striking at the time of writing), in terms of an initial lack of political will to prioritise public health, itself a product of a strong Prime Minister who made the "wrong call". It also highlights a failure to "follow the science", except in so far as the "science" had already accepted some dubious political judgements and the lack of capacity to test as the starting-point

Stereochemical Considerations in Triterpenoid Chemistry

Abstract Not Provided

The accuracy of diagnosis of myocardial infarction: a clinico-pathological study

(1) The 266 post -mortem records of those found to have died from or suspected of dying from myocardial infarction in The Royal Infirmary, Edinburgh, in 1954. and 1955 have been reviewed. (2) The accuracy rate in the diagnosis of myocardial infarction is surprisingly low, being 44% when the cases only discovered at autopsy are taken into account. The major diagnostic errors occur in patients who died suddenly or present in an atypical way. (3) A greater awareness of the possibility of underlying myocardial infarction in elderly patients with unexplained heart failure or pleural effusions, in cases with cerebrovascular accidents, and in post- operative patients whose condition inexplicably deteriorates might lead to a decrease in diagnostic errors. (4) About 50 of sudden deaths are due to myocardial infarction; and anyone who dies suddenly having given previous evidence, either clinical or electrocardiographic, of coronary artery disease, is almost certain to have died in this way. The electrocardiographic diagnosis of recent myocardial infarction is very accurate, and a clinical diagnosis alone without electrocardiographic corroboration, when this is available, is no longer justifiable

Development of primary invasive pneumococcal disease caused by serotype 1 pneumococci is driven by early increased type I interferon response in the lung

The pneumococcus is the world's foremost respiratory pathogen, but the mechanisms allowing this pathogen to proceed from initial asymptomatic colonization to invasive disease are poorly understood. We have examined the early stages of invasive pneumococcal disease (IPD) by comparing host transcriptional responses to an invasive strain and a noninvasive strain of serotype 1 Streptococcus pneumoniae in the mouse lung. While the two strains were present in equal numbers in the lung 6 h after intranasal challenge, only the invasive strain (strain 1861) had invaded the pleural cavity at that time point; this correlated with subsequent development of bacteremia in mice challenged with strain 1861 but not the noninvasive strain (strain 1). Progression beyond the lung was associated with stronger induction of the type I interferon (IFN-I) response in the lung at 6 h. Suppression of the IFN-I response through administration of neutralizing antibody to IFNAR1 (the receptor for type I interferons) led to significantly reduced invasion of the pleural cavity by strain 1861 at 6 h postchallenge. Our data suggest that strong induction of the IFN-I response is a key factor in early progression of invasive serotype 1 strain 1861 beyond the lung during development of IPD