Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection

Introduction: Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. Whilst the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance evidence of the effect on outcome following severe infection is lacking. Methods: In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following gram-negative bacteraemia in the 2-year period around implementation. Results: Introduction of restrictive antibiotic guidelines was associated with a reduction in utilisation of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. 1593 episodes of bacteraemia were included in the study. The mortality over 1 year following gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. Conclusion: Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following gram-negative bacteraemia. There was a small reduction in one year mortality

The phenotypic, genotypic and transcriptomic characterisation of a novel Pseudomonas aeruginosa small colony variant isolated from a chronic murine infection model

No abstract available

Contextual factors and programme theories associated with implementing blue prescription programmes: a systematic realist review.

Nature-based social prescribing such as "blue prescription" promotes public health and health improvement of individuals with long-term health conditions. However, there is limited evidence explaining the relationship of contexts, mechanisms, and outcomes of implementing blue prescription programmes (BPPs) in health and social care settings that could inform policy and practice. We conducted a systematic realist review by searching PubMed, Web of Science, PsycInfo, Scopus, MEDLINE, and CINAHL for articles published in English between January 2000 and June 2022 about health and social care professionals providing referral to or prescription of blue space activities (e.g., swimming, fishing, surfing, etc.) with health-related outcomes. Components and descriptions of BPP implementation were extracted and used to develop themes of contextual factors used to develop programme theories and a logic model demonstrating the mechanisms of BPP implementation. Sixteen studies with adequate to strong quality were included from 8,619 records. After participating in BPPs referred to or prescribed by health and social care professionals, service users had improvements in their physical, cognitive (mental), social health, and proenvironmental knowledge. Service user-related contextual factors were referral information, free equipment, transportation, social support, blue space environments, and skills of service providers. Programme-related contextual factors were communication, multistakeholder collaboration, financing, and adequate service providers. Programme theories on service user enrolment, engagement, adherence, communication protocols, and programme sustainability explain the mechanisms of BPP implementation. BPPs could promote health and wellbeing if contextual factors and programme theories associated with service users' characteristics and programme delivery are considered in the design, delivery, and evaluation of BPPs. The study was registered with PROSPERO (CRD42020170660)

Genomic and transcriptomic characterization of Pseudomonas aeruginosa small colony variants derived from a chronic infection model

Phenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis, well-characterized phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoid P. aeruginosa strain NH57388A. Using a combination of single-molecule real-time (PacBio) and Illumina sequencing we identify a large genomic inversion in the SCV through recombination between homologous regions of two rRNA operons and an associated truncation of one of the 16S rRNA genes and suggest this may be the genetic switch for conversion to the SCV phenotype. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance because the appearance of SCVs during chronic infection is associated with declining lung function

Taking an evaluative stance to decision-making about professional development options in early childhood education and care

This article builds on our ongoing work in conceptualising an ‘evaluative stance’ framework to assist in understanding how leaders in the field of early childhood education and care (ECEC) make decisions about the selection of professional development options for themselves and their staff. It introduces the notion that evaluative mindsets can be considered in terms of attitudes towards decision-making that are based on personal epistemologies. Drawing on data from semi-structured interviews, it explores the mindsets of six experienced leaders in two long-established ECEC organisations in Australia with respect to their decision-making about professional development. The article concludes with a consideration of the potential utility of the framework and the coding template used in this exploratory study

Measuring “waiting” impulsivity in substance addictions and binge eating disorder in a novel analogue of rodent serial reaction time task

Background Premature responding is a form of motor impulsivity that preclinical evidence has shown to predict compulsive drug seeking but has not yet been studied in humans. We developed a novel translation of the task, based on the rodent 5-choice serial reaction time task, testing premature responding in disorders of drug and natural food rewards. Methods Abstinent alcohol- (n = 30) and methamphetamine-dependent (n = 23) subjects, recreational cannabis users (n = 30), and obese subjects with (n = 30) and without (n = 30) binge eating disorder (BED) were compared with matched healthy volunteers and tested on the premature responding task. Results Compared with healthy volunteers, alcohol- and methamphetamine-dependent subjects and cannabis users showed greater premature responding with no differences observed in obese subjects with or without BED. Current smokers exhibited greater premature responding versus ex-smokers and nonsmokers. Alcohol-dependent subjects also had lower motivation for explicit monetary incentives. A Motivation Index correlated negatively with alcohol use and binge eating severity. Conclusions Premature responding on a novel translation of a serial reaction time task was more evident in substance use disorders but not in obese subjects with or without BED. Lower motivation for monetary incentives linked alcohol use and binge eating severity. Our findings add to understanding the relationship between drug and natural food rewards

Hereditary haemochromatosis, haemophagocytic lymphohistiocytosis and COVID-19

Background Syndromes of iron overload have been shown to increase the risk severe clinical disease in viral infections. Immune dysfunction is similarly described in hereditary haemochromatosis (HH). We present here the case of a 51-year-old man who developed severe coronavirus disease 2019 (COVID-19) complicated by suspected haemophagocytic lymphohistiocytosis (HLH). He was found to have HH post-mortem and we propose a link between his iron overload and the development of severe COVID-19. Case report The initial clinical presentation consisted of cough, shortness of breath and fever. Pancytopenia, markedly elevated ferritin and d-dimer were present. Computed tomography (CT) showed bilateral ground glass changes consistent with COVID-19, widespread lymphadenopathy and splenomegaly. A subsequent combined nose and throat swab was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). HLH was suspected based upon the H-score and Anakinra, an IL-1 receptor antagonist, was commenced. Liver function acutely worsened and magnetic resonance cholangiopancreatography (MRCP) revealed hepatic haemosiderosis. Intense splenic and cervical lymph node uptake were seen on a positron emission tomography (PET) scan and high doses of intravenous steroids were administered due to concerns over haematological malignancy. Results Day fourteen of admission heralded the start of progressive clinical deterioration with rapid increase in oxygen demands. Continuous positive airway pressure (CPAP) was trialled without success and the patient unfortunately died seventeen days into admission. Results returned after his death showed homozygous C282Y mutation of the HFE gene consistent with a diagnosis of HH. Post-mortem examination revealed widespread haemosiderin deposition in the liver along with lung pathology in keeping with severe COVID-19 and widespread splenic infarctions. Conclusion An association between HH and COVID-19 is not currently described in the literature. What does exist, however, is an evidence base for the detrimental impacts iron overload has on viral infections in general and the negative effects of HH on the immune system. We therefore postulate that the underlying metabolic and immune disturbances seen in HH should be considered a potential risk factor for the development of severe COVID-19. This case also adds to the evidence that hyperinflammation appears to be a unique and interesting characteristic of this novel viral disease

Contextual factors and programme theories associated with implementing blue prescription programmes: a systematic realist review

Nature-based social prescribing such as “blue prescription” promotes public health and health improvement of individuals with long-term health conditions. However, there is limited evidence explaining the relationship of contexts, mechanisms, and outcomes of implementing blue prescription programmes (BPPs) in health and social care settings that could inform policy and practice. We conducted a systematic realist review by searching PubMed, Web of Science, PsycInfo, Scopus, MEDLINE, and CINAHL for articles published in English between January 2000 and June 2022 about health and social care professionals providing referral to or prescription of blue space activities (e.g., swimming, fishing, surfing, etc.) with health-related outcomes. Components and descriptions of BPP implementation were extracted and used to develop themes of contextual factors used to develop programme theories and a logic model demonstrating the mechanisms of BPP implementation. Sixteen studies with adequate to strong quality were included from 8,619 records. After participating in BPPs referred to or prescribed by health and social care professionals, service users had improvements in their physical, cognitive (mental), social health, and proenvironmental knowledge. Service user-related contextual factors were referral information, free equipment, transportation, social support, blue space environments, and skills of service providers. Programme-related contextual factors were communication, multistakeholder collaboration, financing, and adequate service providers. Programme theories on service user enrolment, engagement, adherence, communication protocols, and programme sustainability explain the mechanisms of BPP implementation. BPPs could promote health and wellbeing if contextual factors and programme theories associated with service users’ characteristics and programme delivery are considered in the design, delivery, and evaluation of BPPs. Our study was registered with PROSPERO (CRD42020170660)