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.

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.

A framework for ensuring a balanced accounting of the impact of antimicrobial stewardship interventions.

Drawing on a Cochrane systematic review, this paper examines the relatively limited range of outcomes measured in published evaluations of antimicrobial stewardship interventions (ASIs) in hospitals. We describe a structured framework for considering the range of consequences that ASIs can have, in terms of their desirability and the extent to which they were expected when planning an ASI: expected, desirable consequences (intervention goals); expected, undesirable consequences (intervention trade-offs); unexpected, undesirable consequences (unpleasant surprises); and unexpected, desirable consequences (pleasant surprises). Of 49 randomized controlled trials identified by the Cochrane review, 28 (57%) pre-specified increased length of stay and/or mortality as potential trade-offs of ASI, with measurement intended to provide reassurance about safety. In actuality, some studies found unexpected decreases in length of stay (a pleasant surprise). In contrast, only 11 (10%) of 110 interrupted time series studies included any information about unintended consequences, with 10 examining unexpected, undesirable outcomes (unpleasant surprises) using case-control, qualitative or cohort designs. Overall, a large proportion of the ASIs reported in the literature only assess impact on their targeted process goals-antimicrobial prescribing-with limited examination of other potential outcomes, including microbial and clinical outcomes. Achieving a balanced accounting of the impact of an ASI requires careful consideration of expected undesirable effects (potential trade-offs) from the outset, and more consideration of unexpected effects after implementation (both pleasant and unpleasant surprises, although the latter will often be more important). The proposed framework supports the systematic consideration of all types of consequences of improvement before and after implementation.

Time series analysis of the impact of an intervention in Tayside, Scotland to reduce primary care broad-spectrum antimicrobial use.

OBJECTIVES: Concern about Clostridium difficile infection (CDI) and resistance has driven interventions internationally to reduce broad-spectrum antimicrobial use. An intervention combining guidelines, education and feedback was implemented in Tayside, Scotland in 2009 aiming to reduce primary care prescribing of co-amoxiclav, cephalosporins, fluoroquinolones and clindamycin ('4C antimicrobials'). Our aim was to assess the impact of this real-world intervention on antimicrobial prescribing rates. METHODS: We used interrupted time series with segmented regression analysis to examine associations between the intervention and changes in antimicrobial prescribing (quarterly rates of patients exposed to 4C antimicrobials, non-4C antimicrobials and any antimicrobial in 2005-12). RESULTS: The intervention was associated with a highly significant and sustained decrease in 4C antimicrobial prescribing, by 33.5% (95% CI -26.1 to -40.9), 42.2% (95% CI -34.2 to -50.2) and 55.5% (95% CI -45.9 to -65.1) at 6, 12 and 24 months after intervention, respectively. The effect was seen across all age groups, with the largest reductions in people aged 65 years and over (58.4% reduction at 24 months, 95% CI -46.7 to -70.1) and care home residents (65.6% reduction at 24 months, 95% CI -51.8 to -79.4). There were balancing increases in doxycycline, nitrofurantoin and trimethoprim prescribing as well as a reduction in macrolide prescribing. Total antimicrobial exposure did not change. CONCLUSIONS: A real-world intervention to reduce primary care prescribing of antimicrobials associated with CDI led to large, sustained reductions in the targeted prescribing, largely due to substitution with guideline-recommended antimicrobials rather than by avoiding antimicrobial use altogether. Further research is needed to examine the impact on antimicrobial resistance.

Identifying which septic patients have increased mortality risk using severity scores: a cohort study.

BACKGROUND: Early aggressive therapy can reduce the mortality associated with severe sepsis but this relies on prompt recognition, which is hindered by variation among published severity criteria. Our aim was to test the performance of different severity scores in predicting mortality among a cohort of hospital inpatients with sepsis. METHODS: We anonymously linked routine outcome data to a cohort of prospectively identified adult hospital inpatients with sepsis, and used logistic regression to identify associations between mortality and demographic variables, clinical factors including blood culture results, and six sets of severity criteria. We calculated performance characteristics, including area under receiver operating characteristic curves (AUROC), of each set of severity criteria in predicting mortality. RESULTS: Overall mortality was 19.4% (124/640) at 30 days after sepsis onset. In adjusted analysis, older age (odds ratio 5.79 (95% CI 2.87-11.70) for ≥80y versus <60y), having been admitted as an emergency (OR 3.91 (1.31-11.70) versus electively), and longer inpatient stay prior to sepsis onset (OR 2.90 (1.41-5.94) for >21d versus <4d), were associated with increased 30 day mortality. Being in a surgical or orthopaedic, versus medical, ward was associated with lower mortality (OR 0.47 (0.27-0.81) and 0.26 (0.11-0.63), respectively). Blood culture results (positive vs. negative) were not significantly association with mortality. All severity scores predicted mortality but performance varied. The CURB65 community-acquired pneumonia severity score had the best performance characteristics (sensitivity 81%, specificity 52%, positive predictive value 29%, negative predictive value 92%, for 30 day mortality), including having the largest AUROC curve (0.72, 95% CI 0.67-0.77). CONCLUSIONS: The CURB65 pneumonia severity score outperformed five other severity scores in predicting risk of death among a cohort of hospital inpatients with sepsis. The utility of the CURB65 score for risk-stratifying patients with sepsis in clinical practice will depend on replicating these findings in a validation cohort including patients with sepsis on admission to hospital.

Community-associated Clostridium difficile infection among older people in Tayside, Scotland, is associated with antibiotic exposure and care home residence: cohort study with nested case-control.

OBJECTIVES: To estimate the risks of community-associated Clostridium difficile infection (CA-CDI) among the population aged ≥ 65 years associated with antibiotic exposure and care home residence. POPULATION AND METHODS: We linked cases from a prospective study in Tayside, Scotland from 1 November 2008 to 31 October 2009 to population datasets to conduct a cohort study and a nested, matched (1 : 10 by age and gender) case-control study. RESULTS: There were 79,039 eligible residents. CA-CDI incidence was 20.3/10,000 person years. In the cohort study, after adjustment, we found a significantly increasing risk of CA-CDI with increasing age and comorbidity, prior hospital admission, care home residence [hazard ratio (HR) 1.96, 95% CI 1.14-3.34] and baseline antibiotic exposure (1.94, 1.35-2.77). In separate adjusted models, '4C' antibiotics (clindamycin, co-amoxiclav, cephalosporins, ciprofloxacin; 2.75, 1.78-4.26) and fluoroquinolones (3.33, 1.95-5.67) had higher associated risks. We matched 62 CA-CDI cases without recent (prior 3 months) hospital admission to 620 controls. In adjusted logistic regression models, exposure to any antibiotics increased the risk of CA-CDI (OR 6.04, 95% CI 3.19-11.43). Exposure to 4C antibiotics or fluoroquinolones had higher associated risks: adjusted OR 11.60 (95% CI 5.57-24.15) and 13.04 (4.91-34.64), respectively. Risk of CA-CDI increased with cumulative antibiotic exposure. Subgroup analysis of 42 cases with C. difficile cultured and 420 controls amplified all associations between antibiotic exposure and CA-CDI. Care home residence independently increased the risk of CA-CDI in all models. CONCLUSIONS: Our results have two important implications. First, they validate the classification of 4C antibiotics and fluoroquinolones in primary care as high risk for CA-CDI. Second, they demonstrate the importance of prior antibiotic exposure and place of residence for risk assessment by primary care prescribers.

Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe.

BACKGROUND: The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS). METHODS AND FINDINGS: The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future. CONCLUSIONS: Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern.

Clinical impact of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay related to methicillin-resistant Staphylococcus aureus bloodstream infections.

Antimicrobial resistance is threatening the successful management of nosocomial infections worldwide. Despite the therapeutic limitations imposed by methicillin-resistant Staphylococcus aureus (MRSA), its clinical impact is still debated. The objective of this study was to estimate the excess mortality and length of hospital stay (LOS) associated with MRSA bloodstream infections (BSI) in European hospitals. Between July 2007 and June 2008, a multicenter, prospective, parallel matched-cohort study was carried out in 13 tertiary care hospitals in as many European countries. Cohort I consisted of patients with MRSA BSI and cohort II of patients with methicillin-susceptible S. aureus (MSSA) BSI. The patients in both cohorts were matched for LOS prior to the onset of BSI with patients free of the respective BSI. Cohort I consisted of 248 MRSA patients and 453 controls and cohort II of 618 MSSA patients and 1,170 controls. Compared to the controls, MRSA patients had higher 30-day mortality (adjusted odds ratio [aOR] = 4.4) and higher hospital mortality (adjusted hazard ratio [aHR] = 3.5). Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR = 2.4) and hospital (aHR = 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR = 1.8; P = 0.04), but not for hospital mortality (HR = 1.1; P = 0.63) or LOS (difference = 0.6 days; P = 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.

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.

The information and support needs of patients discharged after a short hospital stay for treatment of low-risk Community Acquired Pneumonia: implications for treatment without admission.

BACKGROUND: There is increasing evidence that patients with low-risk community acquired pneumonia (CAP) can be effectively treated as outpatients. This study aimed to explore patients' experiences of having pneumonia and seeking health care; their perceptions of the information provided by health professionals; how they self managed at home; their information and support needs; and their beliefs and preferences regarding site of care. METHODS: We conducted qualitative, semi-structured interviews with 15 patients who had a confirmed diagnosis of low-risk CAP and had received fewer than 3 days hospital care. Interviews were audio recorded and transcribed, and data were analysed thematically. RESULTS: Most patients left hospital with no clear understanding of pneumonia, its treatment or follow-up and most identified additional-other specific information needs when they got home. Some were unable to independently address their activities of daily living in their first days at home.Main concerns after discharge related to the cause and implications of pneumonia, symptom trajectory and prevention of transmission. Most sought advice from their GP in their first days at home, and indicated they would have appreciated a follow-up phone call or visit to discuss their concerns.Patients' preferences for site of care varied and appeared to be influenced by beliefs about safety (fear of rapid deterioration at home or acquiring an infection in hospital), family burden, access to support, or confidence in home-care services. Those who received intravenous (IV) medication were more likely to state a preference for hospital care. CONCLUSION: Trends to support community-based treatment of CAP should be accompanied by increased attention to the information and support needs of patients who go home to self-manage. Although some information needs can be anticipated and addressed on diagnosis, specific needs often do not become apparent until patients return home, so some access to information and support in the community is likely to be necessary. Our finding that patients who received IV treatment for low-risk CAP were concerned about the relative safety of home-based care highlights the potential importance of the inferences patients make from treatment modalities, and also the need to ensure that patients' expectations and understandings are managed effectively.

The ORION statement: guidelines for transparent reporting of outbreak reports and intervention studies of nosocomial infection.

The quality of research in hospital epidemiology (infection control) must be improved to be robust enough to influence policy and practice. In order to raise the standards of research and publication, a CONSORT equivalent for these largely quasi-experimental studies has been prepared by the authors of two relevant systematic reviews, following consultation with learned societies, editors of journals, and researchers. The ORION (Outbreak Reports and Intervention Studies Of Nosocomial infection) statement consists of a 22 item checklist, and a summary table. The emphasis is on transparency to improve the quality of reporting and on the use of appropriate statistical techniques. The statement has been endorsed by a number of professional special interest groups and societies. Like CONSORT, ORION should be considered a "work in progress", which requires ongoing dialogue for successful promotion and dissemination. The statement is therefore offered for further public discussion. Journals and research councils are strongly recommended to incorporate it into their submission and reviewing processes. Feedback to the authors is encouraged and the statement will be revised in 2 years.

Locality deprivation and Type 2 diabetes incidence: a local test of relative inequalities.

There is increasing evidence that the socio-spatial context of the local area in which one lives can have an effect on health, but teasing out contextual influences is not a simple task. We examine whether the incidence of Type 2 diabetes in small areas in Tayside, Scotland is associated with deprivation in neighbouring areas, controlling for the deprivation of the area itself. As such, this is a genuinely 'contextual' variable situating each small area in the context of surrounding places. We test two opposing hypotheses. First, a 'psycho-social' hypothesis might suggest that negative social comparisons made by individuals in relation to those who surround them could lead to chronic low-level stress via psycho-social pathways, the physiological effects of which could promote diabetes. Thus, we would expect people living in deprived areas surrounded by less deprived areas to have an increased risk of diabetes, compared to those living in similarly deprived areas that are surrounded by equally or more deprived areas. Alternatively, a neo-materialist approach might suggest that the social, cultural and environmental resources in the surrounding environment will influence circumstances in a particular area of interest. Poorer areas surrounded by less deprived areas would benefit from the better resources in the wider locality, while less deprived areas surrounded by poorer areas may be hampered by the poorer resources available nearby. We refer to this as the 'pull-up/pull-down' hypothesis. Our results show that, as expected, area deprivation is positively related to diabetes incidence (p<0.001), whilst deprivation inequality between areas and their neighbours is negatively related (p=0.006). Type 2 diabetes is more common in deprived areas, but lower in deprived areas that are surrounded by relatively less deprived areas. On the other hand, less deprived areas that are surrounded by relatively more deprived areas have higher diabetes incidence than would be expected from the deprivation of the area alone. Our model results are consistent with a pull-up/pull-down model and lend no support to a 'psycho-social' interpretation at this local scale of analysis.

Evaluation of outcomes in community-acquired pneumonia: a guide for patients, physicians, and policy-makers.

Community-acquired pneumonia (CAP) is a key target for research and quality improvement in acute medicine. However, many of the outcome measures used in prognostic and antibiotic studies are not validated and do not capture features of outcome that are important to patients. Substitutes for traditional outcome measures include a recently validated patient-based symptom questionnaire (the CAP-Sym) and process-of-care measures. The interpretation of outcomes also depends on the quality of the study design and methods used. This paper discusses the advantages and disadvantages of outcome, process-of-care, and economic measures in CAP and the interpretation of these measures in randomised and observational studies. A core set of measures for use in clinical CAP research and performance measurement is proposed.

Educational interventions to improve antibiotic use in the community: report from the International Forum on Antibiotic Resistance (IFAR) colloquium, 2002.

National and international strategies for the control of antibiotic resistance recommend education for health-care professionals and the public to promote prudent antibiotic use. This paper, based on discussions at the 2002 colloquium of the International Forum on Antibiotic Resistance (IFAR), provides an international discourse between theoretical approaches to behaviour change and practical experience gained in large-scale antibiotic use educational campaigns. Interventions are more likely to be effective if their aim is to change behaviour, rather than provide information. They should target all relevant groups, especially parents, children, day-care staff, and health-care professionals. They should use clear and consistent messages concerning bacterial versus viral infection, prudent antibiotic use, symptomatic treatment, and infection-control measures (eg, handwashing). Campaigns should use a range of communications using pilot-testing, strong branding, and sociocultural adaptation. Prime-time television is likely to be the most effective public medium, while academic detailing is especially useful for health-care professionals. Multifaceted interventions can improve antibiotic prescribing to some degree. However, there are few data on their effects on resistance patterns and patient outcomes, and on their cost-effectiveness. Current research aims include the application of behaviour-change models, the development and validation of prudent antibiotic prescribing standards, and the refinement of tools to assess educational interventions.

Education in pharmacoeconomics: an international multidisciplinary view.

There is a global need for more training in pharmacoeconomics. Pharmacoeconomics is a relatively new discipline that draws from other more established disciplines; hence, multidisciplinary collaboration is recommended. Descriptions of opportunities for pharmacoeconomics education can be found in the literature and on websites, but research on the trends in pharmacoeconomics education is largely limited to training in US pharmacy schools. Although basic pharmacoeconomics concepts and methods can be standardised for different countries and cultures, specific applications and examples will differ by region. There are also different levels of educational need (awareness, application, conceptualisation) and different methods of receiving pharmacoeconomics education (short courses, internships, fellowships, graduate degrees). In order to assess educational goals, some educational programmes have moved toward the concept of developing and measuring 'learning outcomes', defined as the knowledge, skills and attitudes needed to fulfil the societal roles expected of the learner. This method can improve the standardisation of the educational process; however, there is still much work to be done in order to achieve real consensus on 'learning outcomes' in pharmacoeconomics.

A multifaceted intervention to improve sepsis management in general hospital wards with evaluation using segmented regression of interrupted time series.

PROBLEM: Antibiotic administration to inpatients developing sepsis in general hospital wards was frequently delayed. We aimed to reproduce improvements in sepsis management reported in other settings. CONTEXT: Ninewells Hospital, an 860-bed teaching hospital with quality improvement (QI) experience, in Scotland, UK. The intervention wards were 22 medical, surgical and orthopaedic inpatient wards. DESIGN: A multifaceted intervention, informed by baseline process data and questionnaires and interviews with junior doctors, evaluated using segmented regression analysis of interrupted time series (ITS) data. MEASURES FOR IMPROVEMENT: Primary outcome measure: antibiotic administration within 4 hours of sepsis onset. Secondary measures: antibiotics within 8 hours; mean and median time to antibiotics; medical review within 30 min for patients with a standardised early warning system score .4; blood cultures taken before antibiotic administration; blood lactate level measured. STRATEGIES FOR CHANGE: The intervention included printed and electronic clinical guidance, educational clinical team meetings including baseline performance data, audit and monthly feedback on performance. EFFECTS OF CHANGE: Performance against all study outcome measures improved postintervention but differences were small and ITS analysis did not attribute the observed changes to the intervention. LESSONS LEARNT: Rigorous analysis of this carefully designed improvement intervention could not confirm significant effects. Statistical analysis of many such studies is inadequate, and there is insufficient reporting of negative studies. In light of recent evidence, involving senior clinical team members in verbal feedback and action planning may have made the intervention more effective. Our focus on rigorous intervention design and evaluation was at the expense of iterative refinement, which likely reduced the effect. This highlights the necessary, but challenging, requirement to invest in all three components for effective QI.

Trimethoprim prescription and subsequent resistance in childhood urinary infection: multilevel modelling analysis.

BACKGROUND: Antibiotic resistance is a growing concern and antibiotic usage the main contributing factor, but there are few studies examining antibiotic use and resistance in children. AIM: To investigate the association between previous trimethoprim prescribing and resistance in urinary Escherichia coli (E. coli) isolates in children. DESIGN AND SETTING: Retrospective, population cohort study in Tayside, Scotland. METHOD: Multilevel modelling of linked microbiology and dispensed prescribing data for 1373 ≤16-year-olds with E. coli urinary isolates in 2004-2009, examining the association between prior trimethoprim prescription and subsequent trimethoprim resistance in people with urinary E. coli isolates. RESULTS: Trimethoprim resistance was common (26.6%, 95% confidence interval [CI] = 24.6 to 28.6). Previous trimethoprim prescription was associated with subsequent culture of trimethoprim-resistant E. coli, with more recent prescription being more strongly associated with resistance. After adjusting for the number of previous E. coli isolates and sample year, trimethoprim prescribing in the previous 84 days remained significantly associated with culturing trimethoprim-resistant E. coli (adjusted OR 4.71, 95% CI = 1.83 to 12.16 for the previous 15-28 days versus never prescribed; adjusted OR 3.16, 95% CI = 1.63 to 6.13 for the previous 29-84 days); however, associations were not statistically significant for longer periods since prior exposure. CONCLUSION: Trimethoprim prescription has implications for future resistance in individual children, as well as at population level. Clinicians must ensure appropriateness of treatment choice and duration, and alternative antibiotics should be considered for childhood urinary tract infections if trimethoprim has been prescribed in the preceding 3 months.