Role of public health professionals in the climate and ecological crisis: a qualitative study.

BACKGROUND: The climate and ecological emergency is the single biggest health threat facing humanity, yet it is not clear to what extent the public health workforce have been involved in work on this topic. This research aimed to establish what public health consultants working in local authorities in England perceive their role to be, whether the climate crisis is seen as a core component of public health and to identify barriers to action. METHODS: Semi-structured interviews were undertaken with a purposive sample (n=11) of local authority public health consultants in England. Participants were recruited via public health organisations, social media or snowballing. Thematic content analysis was used to identify codes and themes. RESULTS: Public health professionals have started work on climate change but reported being unclear about their role and feeling isolated working on this topic. Barriers to action included shortage of financial resources, communication tools and capacity, limited sharing of best practice, lack of local expertise and conflict between the need for action on climate change and other urgent issues. CONCLUSION: We highlight the need to urgently address existing barriers to enable this important part of the public health workforce to play their role in tackling the climate and ecological crisis.

Genome sequence and silkomics of the spindle ermine moth, Yponomeuta cagnagella, representing the early diverging lineage of the ditrysian Lepidoptera.

Many lepidopteran species produce silk, cocoons, feeding tubes, or nests for protection from predators and parasites for caterpillars and pupae. Yet, the number of lepidopteran species whose silk composition has been studied in detail is very small, because the genes encoding the major structural silk proteins tend to be large and repetitive, making their assembly and sequence analysis difficult. Here we have analyzed the silk of Yponomeuta cagnagella, which represents one of the early diverging lineages of the ditrysian Lepidoptera thus improving the coverage of the order. To obtain a comprehensive list of the Y. cagnagella silk genes, we sequenced and assembled a draft genome using Oxford Nanopore and Illumina technologies. We used a silk-gland transcriptome and a silk proteome to identify major silk components and verified the tissue specificity of expression of individual genes. A detailed annotation of the major genes and their putative products, including their complete sequences and exon-intron structures is provided. The morphology of silk glands and fibers are also shown. This study fills an important gap in our growing understanding of the structure, evolution, and function of silk genes and provides genomic resources for future studies of the chemical ecology of Yponomeuta species.

Improving patient understanding on discharge from the short stay unit: an integrated human factors and quality improvement approach.

This intervention used a systems approach to improve patient understanding on discharge from the adult acute medicine short stay unit (SSU). Patient understanding was assessed across five domains: diagnosis, medication changes, follow-up care, return instructions and knowing who their consultant was. The aim of this approach was that at least 90% of patients achieved near-complete understanding (score >4) on questionnaire across all five discharge domains by the end of April 2021. Pre-intervention most patients received verbal instructions and only a minority received written information. Through staff interviews, we identified the electronic discharge document (EDD) as a practical source of written information. However, testing with patients showed that the format required substantial redesign to be written in patient-friendly language, using signposting, spacing information out and avoiding jargon. The effect of this intervention was assessed with a structured telephone questionnaire, which included both a patient self-rated score and a comparative understanding score to assess true patient understanding of the revised EDD. Pre-intervention 29 discharged patients were interviewed across 10 days and post-intervention 10 patients were interviewed in 7 days. Patients consistently over-rated their understanding of discharge information. Only one patient achieved the aim of comparative understanding >4 across all domains post-intervention. Understanding improved across all but one of the domains, the exception being medication changes. An important unanticipated consequence was that interviews identified inconsistencies in EDD information and gaps in patient understanding, which required escalation to the SSU team. In summary, this intervention improved patient understanding across four of the five domains. However, further work is required on process reliability for the redesigned EDD and on improving understanding of medication changes. Furthermore, the interviews revealed clinically important inconsistencies in EDD information and gaps in patient understanding.

Non-Native Amino Acid Click Chemistry-Based Technology for Site-Specific Polysaccharide Conjugation to a Bacterial Protein Serving as Both Carrier and Vaccine Antigen.

Surface-expressed bacterial polysaccharides are important vaccine antigens but must be conjugated to a carrier protein for efficient antigen presentation and development of strong memory B cell and antibody responses, especially in young children. The commonly used protein carriers include tetanus toxoid (TT), diphtheria toxoid (DT), and its derivative CRM197, but carrier-induced epitopic suppression and bystander interference may limit the expanded use of the same carriers in the pediatric immunization schedule. Recent efforts to develop a vaccine against the major human pathogen group A Streptococcus (GAS) have sought to combine two promising vaccine antigens-the universally conserved group A cell wall carbohydrate (GAC) with the secreted toxin antigen streptolysin O (SLO) as a protein carrier; however, standard reductive amination procedures appeared to destroy function epitopes of the protein, markedly diminishing functional antibody responses. Here, we couple a cell-free protein synthesis (CFPS) platform, allowing the incorporation of non-natural amino acids into a C-terminally truncated SLO toxoid for the precise conjugation to the polyrhamnose backbone of GAC. The combined immunogen generated functional antibodies against both conserved GAS virulence factors and provided protection against systemic GAS challenges. CFPS may represent a scalable method for generating pathogen-specific carrier proteins for multivalent subunit vaccine development.

Improving documentation of prescriptions for as-required medications in hospital inpatients.

It is estimated that 1 in 10 hospital inpatients in Scotland have experienced a medication error. In our unit, an audit in 2019 identified documentation of as-required prescriptions on drug Kardexes as an important target for improvement. This project aimed to reduce the percentage of these errors to <5% in the ward in 6 months.Weekly point prevalence surveys were used to measure medication error rates over a 12-week baseline period. Errors in route, frequency of dose and maximum dose accounted for >80% of all prescribing errors. The intervention was a poster reminder about the three most common errors linked to standards for prescribing pain medication. Barriers to change were identified through inductive thematic analysis of semistructured interviews with five ward doctors and two staff nurses.In the 6 weeks after intervention, our run chart showed a shift in maximum dose errors per patient, which fell from 75% to 26%. However, route and frequency errors remained high at >70% per patient. Most of these errors were due to use of abbreviations, and qualitative interviews revealed that senior doctors and nurses believed that these abbreviations were safe. We found some evidence from national guidelines to support these beliefs.Overall, the intervention was associated with decreased prevalence of patients without a maximum dose written on their prescription, but lack of space on drug prescriptions was identified as a key barrier to further improvement in both maximum dose and abbreviation errors.

Improving access to primary care: a mixed-methods approach studying a new review appointment system in a Scottish GP practice.

A Scottish general practitioner (GP) practice proposed an improvement intervention, shorter pre-bookable 'review' appointments, to increase appointment capacity and meet their patients' demand for appointments. Staff are now able to pre-book these review appointments for patients, guaranteeing that the patient will see the same GP or advanced nurse practitioner (ANP) for both initial and review appointments. By shortening the review appointments, more patients were seen each day, hence the appointment capacity increased. The aim of this project was to examine the impact of the improvement intervention, pre-bookable review appointments, using a mixed-methods approach. Ethnographic methods (non-participant observation, participant observation and eight semistructured interviews with administrative staff) provided qualitative data, to understand the appointment system and to identify areas for further improvement. Quantitative data were then collected to assess: the number of patients receiving 'on the day' appointments, with the aim for this to be 95% (outcome measure); by how much the number of appointments available had increased (process measure) and the administrative staff workload (balancing measure). During a 7-week period, 3 months post-intervention, a median of 93% of patients received an 'on the day' appointment when they phoned for one between 08:00 and 09:00. The number of appointments available increased by 43%. Administrative staff workload (number of calls received per day) remained the same. Patients prefer being able to book in to see the same GP (continuity of care) and the ability to book in advance. Administrative staff workload decreased in terms of dealing with less frustrated patients. Main suggestions for improvement include introducing later appointments for workers and text reminders for pre-booked (review and online) appointments. The introduction of pre-bookable review appointments improved patient accessibility in the practice. Next steps for improving the appointment system include gaining clinician (GP/ANP) opinions on review appointments and trialling later appointments.

Non-clinical immunological comparison of a Next-Generation 24-valent pneumococcal conjugate vaccine (VAX-24) using site-specific carrier protein conjugation to the current standard of care (PCV13 and PPV23).

Despite widespread utilization of pneumococcal conjugate vaccines (PCVs) and the resultant disease reduction, the development of PCVs containing additional serotypes remains a public health priority due to serotype replacement and the resultant shift to non-vaccine containing serotypes. However, incorporating additional serotypes to existing PCVs using conventional technologies has proven problematic. Immune responses to individual serotypes have consistently decreased as more polysaccharide-conjugates are added due to carrier suppression. Using our proprietary cell-free protein synthesis (CFPS) platform, we have successfully produced eCRM® based on the CRM197 sequence for use as an enhanced carrier protein to develop a 24-valent PCV. The eCRM carrier protein contains multiple non-native amino acids (nnAAs) located outside of the primary T-cell epitope regions, thereby enabling site-specific covalent conjugation of the pneumococcal polysaccharides to the nnAAs to consistently expose the critical T-cell epitopes. eCRM also serves to reduce structural heterogeneity associated with classic reductive-amination conjugation while promoting formation of the conjugate matrix structures, the hallmark of PCVs. This process serves to increase the overall polysaccharide:protein ratio, enabling the inclusion of more serotypes while minimizing carrier-mediated immunological interference. The aim of this non-clinical study was to construct a 24-valent PCV and evaluate its immunogenicity. Using the XPressCF® CFPS platform, the eCRM carrier protein was separately conjugated through nnAAs to each of the 24 pneumococcal polysaccharides through click chemistry and mixed with aluminum phosphate to produce VAX-24, Vaxcyte's proprietary PCV preclinical candidate. VAX-24, Prevnar13® and Pneumovax®23 were administered to New Zealand White rabbits to compare the resulting opsonophagocytic activity (OPA) and anti-capsular IgG antibodies. VAX-24 showed conjugate-like immune responses to all 24 serotypes based on comparable OPA and IgG responses to Prevnar13 and higher responses than Pneumovax 23. This study demonstrates the utility of site-specific conjugation technology in a preclinical setting and the potential for a PCV with improved serotype coverage.

Omics-based molecular analyses of adhesion by aquatic invertebrates.

Many aquatic invertebrates are associated with surfaces, using adhesives to attach to the substratum for locomotion, prey capture, reproduction, building or defence. Their intriguing and sophisticated biological glues have been the focus of study for decades. In all but a couple of specific taxa, however, the precise mechanisms by which the bioadhesives stick to surfaces underwater and (in many cases) harden have proved to be elusive. Since the bulk components are known to be based on proteins in most organisms, the opportunities provided by advancing 'omics technologies have revolutionised bioadhesion research. Time-consuming isolation and analysis of single molecules has been either replaced or augmented by the generation of massive data sets that describe the organism's translated genes and proteins. While these new approaches have provided resources and opportunities that have enabled physiological insights and taxonomic comparisons that were not previously possible, they do not provide the complete picture and continued multi-disciplinarity is essential. This review covers the various ways in which 'omics have contributed to our understanding of adhesion by aquatic invertebrates, with new data to illustrate key points. The associated challenges are highlighted and priorities are suggested for future research.

A behavioural approach to specifying interventions: what insights can be gained for the reporting and implementation of interventions to reduce antibiotic use in hospitals?

BACKGROUND: Reducing unnecessary antibiotic exposure is a key strategy in reducing the development and selection of antibiotic-resistant bacteria. Hospital antimicrobial stewardship (AMS) interventions are inherently complex, often requiring multiple healthcare professionals to change multiple behaviours at multiple timepoints along the care pathway. Inaction can arise when roles and responsibilities are unclear. A behavioural perspective can offer insights to maximize the chances of successful implementation. OBJECTIVES: To apply a behavioural framework [the Target Action Context Timing Actors (TACTA) framework] to existing evidence about hospital AMS interventions to specify which key behavioural aspects of interventions are detailed. METHODS: Randomized controlled trials (RCTs) and interrupted time series (ITS) studies with a focus on reducing unnecessary exposure to antibiotics were identified from the most recent Cochrane review of interventions to improve hospital AMS. The TACTA framework was applied to published intervention reports to assess the extent to which key details were reported about what behaviour should be performed, who is responsible for doing it and when, where, how often and with whom it should be performed. RESULTS: The included studies (n = 45; 31 RCTs and 14 ITS studies with 49 outcome measures) reported what should be done, where and to whom. However, key details were missing about who should act (45%) and when (22%). Specification of who should act was missing in 79% of 15 interventions to reduce duration of treatment in continuing-care wards. CONCLUSIONS: The lack of precise specification within AMS interventions limits the generalizability and reproducibility of evidence, hampering efforts to implement AMS interventions in practice.

Barriers and Facilitators to Implementation of Antibiotic Stewardship Programmes in Hospitals in Developed Countries: Insights From Transnational Studies.

Objectives: To identify perceived influences on implementation of antibiotic stewardship programmes (ASPs) in hospitals, across healthcare systems, and to exemplify the use of a behavioral framework to conceptualize those influences. Methods: EMBASE and MEDLINE databases were searched from 01/2001 to 07/2017 and reference lists were screened for transnational studies that reported barriers and/or facilitators to implementing actual or hypothetical ASPs or ASP-supporting strategies. Extracted data were synthesized using content analysis with the Theoretical Domains Framework as an organizing framework. Commonly reported influences were quantified. Results: From 3,196 abstracts 75 full-text articles were screened for inclusion. Eight studies met the eligibility criteria. The number of countries involved in each study ranged from 2 to 36. These studies included a total of 1849 participants. North America, Europe and Australasia had the strongest representation. Participants were members of special interest groups, designated hospital representatives or clinical experts. Ten of the 14 theoretical domains in the framework were present in the results reported in the included studies. The most commonly reported (≥4 out of 8 studies) influences on ASP implementation were coded in the domain "environmental context and resources" (e.g., problems with data and information systems; lack of key personnel; inadequate financial resources) and "goals" (other higher priorities). Conclusions: Despite an extensive transnational research effort, there is evidence from international studies of substantial barriers to implementing ASPs in hospitals, even in developed countries. Large-scale efforts to implement hospital antibiotic stewardship in those countries will need to overcome issues around inadequacy of information systems, unavailability of key personnel and funding, and the competition from other priority initiatives. We have enhanced the evidence base to inform guidance by taking a behavioral approach to identify influences on ASP uptake. Systematic review registration: PROSPERO registration number CRD42017076425.

Assessing the accuracy of ICD-10 coding for measuring rates of and mortality from acute kidney injury and the impact of electronic alerts: an observational cohort study.

BACKGROUND: The application of a uniform definition for acute kidney injury (AKI) is vital to advance understanding and management of AKI. International Classification of Diseases (Tenth Revision) (ICD-10) coding is frequently used to define AKI, but its accuracy is unclear. The aim of this study was to determine whether ICD-10 coding is a reliable method of monitoring rates and outcomes of AKI in inpatients compared with biochemically defined AKI, and whether electronic alerts (e-alerts) for AKI affect ICD-10 AKI coding. METHODS: An observational cohort study of all 505 662 adult admissions to acute hospitals in two Scottish Health Boards [National Health Service (NHS) Tayside and NHS Fife] from January 2013 to April 2017 was performed. AKI e-alerts were implemented in NHS Tayside in April 2015. Sensitivity, specificity, positive and negative predictive values of ICD-10 coding for AKI compared with biochemically defined AKI using the Kidney Disease: Improving Global Outcomes definition and relative risk of 30-day mortality in people with ICD-10 and biochemically defined AKI before and after AKI e-alert implementation were performed. RESULTS: Sensitivity of ICD-10 coding for identifying biochemically defined AKI was very poor in both health boards for all AKI (Tayside 25.7% and Fife 35.8%) and for Stages 2 and 3 AKI (Tayside 43.8% and Fife 53.8%). Positive predictive value was poor both for all AKI (Tayside 76.1% and Fife 45.5%) and for Stages 2 and 3 AKI (Tayside 45.5% and Fife 36.8%). Measured mortality fell following implementation of AKI e-alerts in the ICD-10-coded population but not in the biochemically defined AKI population, reflecting an increase in the proportion of Stage 1 AKI in ICD-10-coded AKI. There was no evidence that the introduction of AKI e-alerts in Tayside improved ICD-10 coding of AKI. CONCLUSION: ICD-10 coding should not be used for monitoring of rates and outcomes of AKI for either research or improvement programmes.

Transcriptional characterisation of the Exaiptasia pallida pedal disc.

BACKGROUND: Biological adhesion (bioadhesion), enables organisms to attach to surfaces as well as to a range of other targets. Bioadhesion evolved numerous times independently and is ubiquitous throughout the kingdoms of life. To date, investigations have focussed on various taxa of animals, plants and bacteria, but the fundamental processes underlying bioadhesion and the degree of conservation in different biological systems remain poorly understood. This study had two aims: 1) To characterise tissue-specific gene regulation in the pedal disc of the model cnidarian Exaiptasia pallida, and 2) to elucidate putative genes involved in pedal disc adhesion. RESULTS: Five hundred and forty-seven genes were differentially expressed in the pedal disc compared to the rest of the animal. Four hundred and twenty-seven genes were significantly upregulated and 120 genes were significantly downregulated. Forty-one condensed gene ontology terms and 19 protein superfamily classifications were enriched in the pedal disc. Eight condensed gene ontology terms and 11 protein superfamily classifications were depleted. Enriched superfamilies were consistent with classifications identified previously as important for the bioadhesion of unrelated marine invertebrates. A host of genes involved in regulation of extracellular matrix generation and degradation were identified, as well as others related to development and immunity. Ab initio prediction identified 173 upregulated genes that putatively code for extracellularly secreted proteins. CONCLUSION: The analytical workflow facilitated identification of genes putatively involved in adhesion, immunity, defence and development of the E. pallida pedal disc. When defence, immunity and development-related genes were identified, those remaining corresponded most closely to formation of the extracellular matrix (ECM), implicating ECM in the adhesion of anemones to surfaces. This study therefore provides a valuable high-throughput resource for the bioadhesion community and lays a foundation for further targeted research to elucidate bioadhesion in the Cnidaria.

Changes in resistance among coliform bacteraemia associated with a primary care antimicrobial stewardship intervention: A population-based interrupted time series study.

BACKGROUND: Primary care antimicrobial stewardship interventions can improve antimicrobial prescribing, but there is less evidence that they reduce rates of resistant infection. This study examined changes in broad-spectrum antimicrobial prescribing in the community and resistance in people admitted to hospital with community-associated coliform bacteraemia associated with a primary care stewardship intervention. METHODS AND FINDINGS: Segmented regression analysis of data on all patients registered with a general practitioner in the National Health Service (NHS) Tayside region in the east of Scotland, UK, from 1 January 2005 to 31 December 2015 was performed, examining associations between a primary care antimicrobial stewardship intervention in 2009 and primary care prescribing of fluoroquinolones, cephalosporins, and co-amoxiclav and resistance to the same three antimicrobials/classes among community-associated coliform bacteraemia. Prescribing outcomes were the rate per 1,000 population prescribed each antimicrobial/class per quarter. Resistance outcomes were proportion of community-associated (first 2 days of hospital admission) coliform (Escherichia coli, Proteus spp., or Klebsiella spp.) bacteraemia among adult (18+ years) patients resistant to each antimicrobial/class. 11.4% of 3,442,205 oral antimicrobial prescriptions dispensed in primary care over the study period were for targeted antimicrobials. There were large, statistically significant reductions in prescribing at 1 year postintervention that were larger by 3 years postintervention when the relative reduction was -68.8% (95% CI -76.3 to -62.1) and the absolute reduction -6.3 (-7.6 to -5.2) people exposed per 1,000 population per quarter for fluoroquinolones; relative -74.0% (-80.3 to -67.9) and absolute reduction -6.1 (-7.2 to -5.2) for cephalosporins; and relative -62.3% (-66.9 to -58.1) and absolute reduction -6.8 (-7.7 to -6.0) for co-amoxiclav, all compared to their prior trends. There were 2,143 eligible bacteraemia episodes involving 2,004 patients over the study period (mean age 73.7 [SD 14.8] years; 51.4% women). There was no increase in community-associated coliform bacteraemia admissions associated with reduced community broad-spectrum antimicrobial use. Resistance to targeted antimicrobials reduced by 3.5 years postintervention compared to prior trends, but this was not statistically significant for co-amoxiclav. Relative and absolute changes were -34.7% (95% CI -52.3 to -10.6) and -63.5 (-131.8 to -12.8) resistant bacteraemia per 1,000 bacteraemia per quarter for fluoroquinolones; -48.3% (-62.7 to -32.3) and -153.1 (-255.7 to -77.0) for cephalosporins; and -17.8% (-47.1 to 20.8) and -63.6 (-206.4 to 42.4) for co-amoxiclav, respectively. Overall, there was reversal of a previously rising rate of fluoroquinolone resistance and flattening of previously rising rates of cephalosporin and co-amoxiclav resistance. The limitations of this study include that associations are not definitive evidence of causation and that potential effects of underlying secular trends in the postintervention period and/or of other interventions occurring simultaneously cannot be definitively excluded. CONCLUSIONS: In this population-based study in Scotland, compared to prior trends, there were very large reductions in community broad-spectrum antimicrobial use associated with the stewardship intervention. In contrast, changes in resistance among coliform bacteraemia were more modest. Prevention of resistance through judicious use of new antimicrobials may be more effective than trying to reverse resistance that has become established.

Risk of acute kidney injury following community prescription of antibiotics: self-controlled case series.

BACKGROUND: Development of acute kidney injury (AKI) following the use of antibiotics such as sulphonamides, trimethoprim and aminoglycosides is a frequently described phenomenon. More recently, an association between fluoroquinolone use and AKI has been suggested. The aim of this study was to evaluate the risk of AKI as an unintended consequence of commonly prescribed antibiotics in a large community cohort using a method that fully adjusts for underlying patient characteristics, including potential unmeasured confounders. METHODS: A self-controlled case study was conducted and included all individuals aged 18 years and over in the Tayside region of Scotland who had a serum creatinine measured between 1 January 2004 and 31 December 2012. AKI episodes were defined using the Kidney Disease: Improving Global Outcomes definition. Data on oral community-prescribed antibiotics (penicillins, cephalosporins, fluoroquinolones, sulphonamides and trimethoprim, macrolides and nitrofurantoin) were collected for all individuals. Incidence rate ratios (IRRs) for AKI associated with antibiotic exposure versus time periods without antibiotic exposure were calculated. RESULTS: Combined use of sulphonamides, trimethoprim and nitrofurantoin rose by 47% and incidence of community-acquired AKI rose by 16% between 2008 and 2012. During the study period 12 777 individuals developed 14 900 episodes of AKI in the community, of which 68% was AKI Stage 1, 16% Stage 2 and 16% Stage 3. The IRR of AKI during any antibiotic use was 1.16 [95% confidence interval (CI) 1.10-1.23], and this was highest during sulphonamides or trimethoprim use; IRR 3.07 (95% CI 2.81-3.35). Fluoroquinolone and nitrofurantoin use was not associated with a significantly increased rate of AKI; IRR 1.13 (95% CI 0.94-1.35) and 1.16 (95% CI 0.91-1.50), respectively. CONCLUSIONS: Incidence of AKI rose by 16% between 2008 and 2012. In the same period the use of sulphonamides, trimethoprim and nitrofurantoin increased by 47%. A significant increased risk of AKI was seen with the use of sulphonamides and trimethoprim, but not with fluoroquinolones or nitrofurantoin.

Effects of peri-operative nonsteroidal anti-inflammatory drugs on post-operative kidney function for adults with normal kidney function.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) provide effective analgesia during the post-operative period but can cause acute kidney injury (AKI) when used peri-operatively (at or around the time of surgery). This is an update of a Cochrane review published in 2007. OBJECTIVES: This review looked at the effect of NSAIDs used in the peri-operative period on post-operative kidney function in patients with normal kidney function. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 4 January 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the use of NSAIDs versus placebo for the treatment of post-operative pain in patients with normal kidney function were included. DATA COLLECTION AND ANALYSIS: Data extraction was carried out independently by two authors as was assessment of risk of bias. Disagreements were resolved by a third author. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). Meta-analyses were used to assess the outcomes of AKI, change in serum creatinine (SCr), urine output, renal replacement therapy (RRT), death (all causes) and length of hospital stay. MAIN RESULTS: We identified 26 studies (8835 participants). Risk of bias was high in 17, unclear in 6and low in three studies. There was high risk of attrition bias in six studies.Only two studies measured AKI. The use of NSAIDs had uncertain effects on the incidence of AKI compared to placebo (7066 participants: RR 1.79, 95% CI 0.40 to 7.96; I2 = 59%; very low certainty evidence). One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group. Moreover, both of these studies were examining NSAIDs for indications other than analgesia and therefore utilised relatively low doses.Compared to placebo, NSAIDs may slightly increase serum SCr (15 studies, 794 participants: MD 3.23 µmol/L, 95% CI -0.80 to 7.26; I2 = 63%; low certainty evidence). Studies displayed moderate to high heterogeneity and had multiple exclusion criteria including age and so were not representative of patients undergoing surgery. Three of these studies excluded patients if their creatinine rose post-operatively.NSAIDs may make little or no difference to post-operative urine output compared to placebo (6 studies, 149 participants: SMD -0.02, 95% CI -0.31 to 0.27). No reliable conclusions could be drawn from these studies due to the differing units of measurements and measurement time points.It is uncertain whether NSAIDs leads to the need for RRT because the certainty of this evidence is very low (2 studies, 7056 participants: RR 1.57, 95% CI 0.49 to 5.07; I2 = 26%); there were few events and the results were inconsistent.It is uncertain whether NSAIDs lead to more deaths (2 studies, 312 participants: RR 1.44, 95% CI 0.19 to 11.12; I2 = 38%) or increased the length of hospital stay (3 studies, 410 participants: MD 0.12 days, 95% CI -0.48 to 0.72; I2 = 24%). AUTHORS' CONCLUSIONS: Overall NSAIDs had uncertain effects on the risk of post-operative AKI, may slightly increase post-operative SCr, and it is uncertain whether NSAIDs lead to the need for RRT, death or increases the length of hospital stay. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further larger studies using the Kidney Disease Improving Global Outcomes definition for AKI including patients with co-morbidities are required to confirm these findings. .

Medical students as agents of change: a qualitative exploratory study.

BACKGROUND: There is evidence that medical students have the potential to actively initiate, lead and bring about change through quality improvement within healthcare organisations. For effective change to occur, it is important that students are introduced to, and exposed to the value and necessity of quality improvement early in their careers. The aim of this study was to explore the perspectives and experiences of medical students and their mentors after undertaking quality improvement projects within the healthcare setting, and if such practice-based experiences were an effective way of building improvement capacity and changing practice. METHODS: A qualitative interpretive description methodology, using focus groups with medical students and semi-structured interviews with academic and clinical mentors following completion of students' 4-week quality improvement projects was adopted. RESULTS: The findings indicate that there are a range of facilitators and barriers to undertaking and completing quality improvement projects in the clinical setting, such as time-scales, differing perspectives, roles and responsibilities between students and multidisciplinary healthcare professionals. CONCLUSIONS: This study has demonstrated that quality improvement experiential learning can develop knowledge and skills among medical students and transform attitudes towards quality improvement. Furthermore, it can also have a positive impact on clinical staff and healthcare organisations. Despite inherent challenges, undertaking quality improvement projects in clinical practice enhances knowledge, understanding and skills, and allows medical students to see themselves as important influencers of change as future doctors.

Interprofessional, student-led intervention to improve insulin prescribing to patients in an Acute Surgical Receiving Unit.

Our aim was to test the feasibility of interprofessional, workplace-based learning about improvement through a 4-week placement for one medical and two pharmacy final year students in an Acute Surgical Receiving Unit (ASRU). The target was insulin because this is a common, high-risk medicine in this ASRU and the intervention was medicines reconciliation. Baseline data were collected from 10 patients and used to construct a cause and effect diagram and a process map through feedback and discussions with staff. Hypoglycaemia occurred in four patients but hyperglycaemia occurred in eight patients, of whom six were placed on intravenous insulin infusion (IVII). We estimated that £2454 could be saved by preventing one patient from going on IVII. The students designed and tested a sticker to improve medicines reconciliation for insulin patients. An online form was created to capture clinician feedback on the layout and usability of the sticker. The intervention was associated with improvements in the reliability of medicines reconciliation. The students' work contributed to a larger project to reduce the risk of hypoglycaemia in the ASRU. This proved beneficial in enabling the students to engage with the clinical team. Nonetheless, it was challenging for students from two Universities to get a shared understanding of improvement methods and work effectively with the clinical team. The students said that they learnt more about quality improvement in a working healthcare environment than they would ever learn in a classroom and they valued the opportunity to work with students from other healthcare backgrounds in practice. Despite the additional staff time required to support students from two Universities, both have supported continuation of this work.

Driving sustainable change in antimicrobial prescribing practice: how can social and behavioural sciences help?

Addressing the growing threat of antimicrobial resistance is, in part, reliant on the complex challenge of changing human behaviour-in terms of reducing inappropriate antibiotic use and preventing infection. Whilst there is no 'one size fits all' recommended behavioural solution for improving antimicrobial stewardship, the behavioural and social sciences offer a range of theories, frameworks, methods and evidence-based principles that can help inform the design of behaviour change interventions that are context-specific and thus more likely to be effective. However, the state-of-the-art in antimicrobial stewardship research and practice suggests that behavioural and social influences are often not given due consideration in the design and evaluation of interventions to improve antimicrobial prescribing. In this paper, we discuss four potential areas where the behavioural and social sciences can help drive more effective and sustained behaviour change in antimicrobial stewardship: (i) defining the problem in behavioural terms and understanding current behaviour in context; (ii) adopting a theory-driven, systematic approach to intervention design; (iii) investigating implementation and sustainability of interventions in practice; and (iv) maximizing learning through evidence synthesis and detailed intervention reporting.

Learning from errors: assessing final year medical students' reflection on safety improvement, five year cohort study.

BACKGROUND: Investigation of real incidents has been consistently identified by expert reviews and student surveys as a potentially valuable teaching resource for medical students. The aim of this study was to adapt a published method to measure resident doctors' reflection on quality improvement and evaluate this as an assessment tool for medical students. METHODS: The design is a cohort study. Medical students were prepared with a tutorial in team based learning format and an online Managing Incident Review course. The reliability of the modified Mayo Evaluation of Reflection on Improvement tool (mMERIT) was analysed with Generalizability G-theory. Long term sustainability of assessment of incident review with mMERIT was tested over five consecutive years. RESULTS: A total of 824 students have completed an incident review using 167 incidents from NHS Tayside's online reporting system. In order to address the academic practice gap students were supervised by Senior Charge Nurses or Consultants on the wards where the incidents had been reported. Inter-rater reliability was considered sufficiently high to have one assessor for each student report. There was no evidence of a gradient in student marks across the academic year. Marks were significantly higher for students who used Section Questions to structure their reports compared with those who did not. In Year 1 of the study 21 (14%) of 153 mMERIT reports were graded as concern. All 21 of these students achieved the required standard on resubmission. Rates of resubmission were lower (3% to 7%) in subsequent years. CONCLUSIONS: We have shown that mMERIT has high reliability with one rater. mMERIT can be used by students as part of a suite of feedback to help supplement their self-assessment on their learning needs and develop insightful practice to drive their development of quality, safety and person centred professional practice. Incident review addresses the need for workplace based learning and use of real life examples of mistakes, which has been identified by previous studies of education about patient safety in medical schools.