Factors that influence clinicians’ decisions to offer intravenous alteplase in acute ischemic stroke patients with uncertain treatment indication:Results of a discrete choice experiment

Background: Treatment with intravenous alteplase for eligible patients with acute ischemic stroke is underused, with variation in treatment rates across the UK. This study sought to elucidate factors influencing variation in clinicians’ decision-making about this thrombolytic treatment. Methods: A discrete choice experiment using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted with UK-based clinicians. Mixed logit regression analyses were conducted on the data. Results: A total of 138 clinicians completed the discrete choice experiment. Seven patient factors were individually predictive of increased likelihood of immediately offering IV alteplase (compared to reference levels in brackets): stroke onset time 2 h 30 min [50 min]; pre-stroke dependency mRS 3 [mRS 4]; systolic blood pressure 185 mm/Hg [140 mm/Hg]; stroke severity scores of NIHSS 5 without aphasia, NIHSS 14 and NIHSS 23 [NIHSS 2 without aphasia]; age 85 [68]; Afro-Caribbean [white]. Factors predictive of withholding treatment with IV alteplase were: age 95 [68]; stroke onset time of 4 h 15 min [50 min]; severe dementia [no memory problems]; SBP 200 mm/Hg [140 mm/Hg]. Three clinician-related factors were predictive of an increased likelihood of offering IV alteplase (perceived robustness of the evidence for IV alteplase; thrombolyzing more patients in the past 12 months; and high discomfort with uncertainty) and one with a decreased likelihood (high clinician comfort with treating patients outside the licensing criteria). Conclusions: Both patient- and clinician-related factors have a major influence on the use of alteplase to treat patients with acute ischemic stroke. Clinicians’ views of the evidence, comfort with uncertainty and treating patients outside the license criteria are important factors to address in programs that seek to reduce variation in care quality regarding treatment with IV alteplase. Further research is needed to further understand the differences in clinical decision-making about treating patients with acute ischemic stroke with IV alteplase

Antibiotic Therapy and the Gut Microbiome:Investigating the Effect of Delivery Route on Gut Pathogens

The contribution of the gut microbiome to human health has long been established, with normal gut microbiota conferring protection against invasive pathogens. Antibiotics can disrupt the microbial balance of the gut, resulting in disease and the development of antimicrobial resistance. The effect of antibiotic administration route on gut dysbiosis remains under-studied to date, with conflicting evidence on the differential effects of oral and parenteral delivery. We have profiled the rat gut microbiome following treatment with commonly prescribed antibiotics (amoxicillin and levofloxacin), via either oral or intravenous administration. Fecal pellets were collected over a 13-day period and bacterial populations were analyzed by 16S rRNA gene sequencing. Significant dysbiosis was observed in all treatment groups, regardless of administration route. More profound dysbiotic effects were observed following amoxicillin treatment than those with levofloxacin, with population richness and diversity significantly reduced, regardless of delivery route. The effect on specific taxonomic groups was assessed, revealing significant disruption following treatment with both antibiotics. Enrichment of a number of groups containing known gut pathogens was observed, in particular, with amoxicillin, such as the family Enterobacteriaceae. Depletion of other commensal groups was also observed. The degree of dysbiosis was significantly reduced toward the end of the sampling period, as bacterial populations began to return to pretreatment composition. Richness and diversity levels appeared to return to pretreatment levels more quickly in intravenous groups, suggesting convenient parenteral delivery systems may have a role to play in reducing longer term gut dysbiosis in the treatment of infection

Factors that influence variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke: results of a discrete choice experiment

Background: Intravenous thrombolysis for patients with acute ischaemic stroke is underused (only 80% of eligible patients receive it) and there is variation in its use across the UK. Previously, variation might have been explained by structural differences; however, continuing variation may reflect differences in clinical decision-making regarding the eligibility of patients for treatment. This variation in decision-making could lead to the underuse, or result in inappropriate use, of thrombolysis. Objectives: To identify the factors which contribute to variation in, and influence, clinicians’ decision-making about treating ischaemic stroke patients with intravenous thrombolysis. Methods: A discrete choice experiment (DCE) using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted to better understand the influence of patient-related and clinician-related factors on clinical decision-making. An online DCE was developed following an iterative five-stage design process. UK-based clinicians involved in final decision-making about thrombolysis were invited to take part via national professional bodies of relevant medical specialties. Mixed-logit regression analyses were conducted. Results: A total of 138 clinicians responded and opted to offer thrombolysis in 31.4% of cases. Seven patient factors were individually predictive of the increased likelihood of offering thrombolysis (compared with reference levels in brackets): stroke onset time of 2 hours 30 minutes (50 minutes); pre-stroke dependency modified Rankin Scale score (mRS) of 3 (mRS4); systolic blood pressure (SBP) of 185 mmHg (140 mmHg); stroke severity scores of National Institutes of Health Stroke Scale (NIHSS) 5 without aphasia, NIHSS 14 and NIHSS 23 (NIHSS 2 without aphasia); age 85 years (65 years); and Afro-Caribbean (white). Factors predictive of not offering thrombolysis were age 95 years; stroke onset time of 4 hours 15 minutes; severe dementia (no memory problems); and SBP of 200 mmHg. Three clinician-related factors were predictive of an increased likelihood of offering thrombolysis (perceived robustness of the evidence for thrombolysis; thrombolysing more patients in the past 12 months; and high discomfort with uncertainty) and one factor was predictive of a decreased likelihood of offering treatment (clinicians’ being comfortable treating patients outside the licensing criteria). Limitations: We anticipated a sample size of 150–200. Nonetheless, the final sample of 138 is good considering that the total population of eligible UK clinicians is relatively small. Furthermore, data from the Royal College of Physicians suggest that our sample is representative of clinicians involved in decision-making about thrombolysis. Conclusions: There was considerable heterogeneity among respondents in thrombolysis decision-making, indicating that clinicians differ in their thresholds for treatment across a number of patient-related factors. Respondents were significantly more likely to treat 85-year-old patients than patients aged 68 years and this probably reflects acceptance of data from Third International Stroke Trial that report benefit for patients aged > 80 years. That respondents were more likely to offer thrombolysis to patients with severe stroke than to patients with mild stroke may indicate uncertainty/concern about the risk/benefit balance in treatment of minor stroke. Findings will be disseminated via peer-review publication and presentation at national/international conferences, and will be linked to training/continuing professional development (CPD) programmes. Future work: The nature of DCE design means that only a subset of potentially influential factors could be explored. Factors not explored in this study warrant future research. Training/CPD should address the impact of non-medical influences on decision-making using evidence-based strategies. Funding: The National Institute for Health Research Health Services and Delivery Research programme

A novel design process for selection of attributes for inclusion in discrete choice experiments: case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke

A discrete choice experiment (DCE) is a method used to elicit participants’ preferences and the relative importance of different attributes and levels within a decision-making process. DCEs have become popular in healthcare; however, approaches to identify the attributes/levels influencing a decision of interest and to selection methods for their inclusion in a DCE are under-reported. Our objectives were: to explore the development process used to select/present attributes/levels from the identified range that may be influential; to describe a systematic and rigorous development process for design of a DCE in the context of thrombolytic therapy for acute stroke; and, to discuss the advantages of our five-stage approach to enhance current guidance for developing DCEs. A five-stage DCE development process was undertaken. Methods employed included literature review, qualitative analysis of interview and ethnographic data, expert panel discussions, a quantitative structured prioritisation (ranking) exercise and pilot testing of the DCE using a ‘think aloud’ approach. The five-stage process reported helped to reduce the list of 22 initial patient-related factors to a final set of nine variable factors and six fixed factors for inclusion in a testable DCE using a vignette model of presentation. In order for the data and conclusions generated by DCEs to be deemed valid, it is crucial that the methods of design and development are documented and reported. This paper has detailed a rigorous and systematic approach to DCE development which may be useful to researchers seeking to establish methods for reducing and prioritising attributes for inclusion in future DCEs.Financial support for this study was provided entirely by a grant from the National Institute for Health Research (NIHR) Health Services and Delivery Research Programme (project number: 12/5001/45)

A novel design process for selection of attributes for inclusion in discrete choice experiments:Case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke

On-line structured prioritisation exercise (SPE). Full survey used to collect data. (DOCX 42 kb

Pseudomonas aeruginosa: Recent advances in vaccine development

Pseudomonas aeruginosa is an important opportunistic human pathogen. Using its arsenal of virulence factors and its intrinsic ability to adapt to new environments, P. aeruginosa causes a range of complicated acute and chronic infections in immunocompromised individuals. Of particular importance are burn wound infections, ventilator-associated pneumonia, and chronic infections in people with cystic fibrosis. Antibiotic resistance has rendered many of these infections challenging to treat and novel therapeutic strategies are limited. Multiple clinical studies using well-characterised virulence factors as vaccine antigens over the last 50 years have fallen short, resulting in no effective vaccination being available for clinical use. Nonetheless, progress has been made in preclinical research, namely, in the realms of antigen discovery, adjuvant use, and novel delivery systems. Herein, we briefly review the scope of P. aeruginosa clinical infections and its major important virulence factors