Promoting medical student engagement with antimicrobial stewardship through involvement in undergraduate research

The National Health Service recognises the importance of research, teaching, and training to the future success of the organisation and medical students are expected to qualify with the necessary clinical, professional, and academic skills to support this. There is a wide variation in the level of cross-specialty engagement with Antimicrobial Stewardship (AMS) & Antimicrobial resistance (AMR) research at UK and international state-of-the-art conferences, with a heterogeneous level of importance also attributed amongst undergraduate and postgraduate training pathways across clinical medicine. It therefore seems apparent that the AMS-AMR agenda needs to be promoted from within specialties, rather than being ‘pushed’ on them as an external agenda, to promote broad ownership and capacity within all clinical specialties that use antimicrobials. This must start early during undergraduate medical training. We investigated whether the use of an online platform designed to facilitate medical student research projects could be utilised to promote undergraduate engagement with AMSAMR at Imperial College School of Medicine between July 2015 and 2016. During this period 12 applicants were appointed to 11 of the 13 advertised projects. So far, students undertaking these projects have achieved: 1 peer-reviewed publication, 3 national oral presentations, 1 national prize, 1 international poster presentation, 3 national poster presentations, and 2 further manuscripts are currently under peer-review. Furthermore, despite the students’ broad career interests there has been a high retention rate with students requesting involvement in further AMS-AMR related activities. Further longitudinal assessment of this tool for promoting undergraduate engagement with AMS-AMR research is now being explored

Movement control of the trunk and pelvis in cerebral palsy diplegia

Core control was quantified using performance measures derived from a computer game driven by rotation and tilt of the trunk and pelvis. Baseline results showed reduced control of tilt in comparison to rotation, and cephalo-caudal reduction of control. Training of pelvic tilt control may improve pelvic kinematics, reducing the risk of developing low back pain

Improving children's social care services: results of a feasability study.

This report sets out the findings of a feasibility study that aimed to understand how to define ‘good’ children’s social care services and how to assess whether they have improved. The intention was for the feasibility study to support a larger project exploring the processes involved in improving children’s social care services. The key findings of the study are: • There is a lack of consistent expectations about outcomes for children’s social care services and what indicators should be used to monitor them. There is mixed evidence about the features that characterise good children’s social care services, and a significant proportion of it is based on expert opinion and has not been tested quantitatively. • Analysis of the relationship between outcome data for children in need collated nationally by the Department for Education and Ofsted ratings of children’s services found very little association. There did not seem to be any pattern in terms of the local authorities that were in the top or bottom percentiles for child outcome. Only one child outcome variable and one workforce variable had a statistically significant relationship with the Ofsted ratings. • Before proceeding with a study exploring how children’s social care services improve, it is important to identify an outcomes framework that a wide range of stakeholders agree is appropriate and to establish a set of indicators that reflect these outcomes and that could be collected and collated at a national level. • The study team concluded that at this time it is not feasible to go ahead with the main project as originally envisaged, and instead to focus on how to create an outcomes framework and establish an appropriate set of indicators

Going places

Journeys. We all make them. Often they take us to exotic places. Sometimes they take us even further. They might take us through time. Or they might take us into a new way of life. There are times too, when we go all over the world and back again only to find that home is, after all, where it’s all happening. This book contains stories about many different types of journey. We hope you will enjoy travelling into it and finding a world that suits you

PCSK9 genetic variants and cognitive abilities:a large-scale Mendelian randomization study

Introduction: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function. Methods: We examined the association of genetic variants in PCSK9 with continuous measures of cognitive ability in UK Biobank. Six independent polymorphisms in PCSK9 were used in up to 337,348 individuals. Results: The PCSK9 allele score was associated with a lower risk of CHD, and weakly with worse log reaction time. Conclusions: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising the potential need for continued pharmacovigilance for patients currently treated with PCSK9 inhibitors

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial

BACKGROUND Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers

Monitoring Healthy Metabolic Trajectories with Nutritional Metabonomics

Metabonomics is a well established analytical approach for the analysis of physiological regulatory processes via the metabolic profiling of biofluids and tissues in living organisms. Its potential is fully exploited in the field of “nutrimetabonomics” that aims at assessing the metabolic effects of active ingredients and foods in individuals. Yet, one of the greatest challenges in nutrition research is to decipher the critical interactions between mammalian organisms and environmental factors, including the gut microbiota. “Nutrimetabonomics” is today foreseen as a powerful approach for future nutritional programs tailored at health maintenance and disease prevention

Air pollution control with semi-infinite programming

Environment issues are more than ever important in a modern society. Complying with stricter legal thresholds on pollution emissions raises an important economic issue. This paper presents some ideas in the use of optimization tools to help in the planning and control of stationary pollution sources. Three main semi-infinite programming approaches are described. The first consists in optimizing an objective function while the pollution level in a given region is kept bellow a given threshold. In the second approach the maximum pollution level in a given region is computed and in the third an air pollution abatement problem is considered. These formulations allow to obtain the best control parameters and the maxima pollution positions, where the sampling stations should be placed. A specific modeling language was used to code four academic problems. Numerical results computed with a semi-infinite programming solver are shown

Yield of comparative genomic hybridization microarray in pediatric neurology practice

OBJECTIVE: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes. METHODS: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records. An assessment of pathogenicity was made for each CNV, based on recent developments in the literature. RESULTS: Forty-seven patients were found to carry a pathogenic CNV, giving an overall diagnostic yield of 8.59%. Certain phenotypes predicted for the presence of a pathogenic CNV, including developmental delay (odds ratio [OR] 3.69 [1.30–10.51]), cortical visual impairment (OR 2.73 [1.18–6.28]), dysmorphism (OR 2.75 [1.38–5.50]), and microcephaly (OR 2.16 [1.01–4.61]). The combination of developmental delay/intellectual disability with dysmorphism and abnormal head circumference was also predictive for a pathogenic CNV (OR 2.86 [1.02–8.00]). For every additional clinical feature, there was an increased likelihood of detecting a pathogenic CNV (OR 1.18 [1.01–1.38]). CONCLUSIONS: the use of aCGH led to a pathogenic finding in 8.59% of patients. The results support the use of aCGH as a first tier investigation in children with diverse neurologic disorders, although whole-genome sequencing may replace aCGH as the detection method in the future. In particular, the yield was increased in children with developmental delay, dysmorphism, cortical visual impairment, and microcephaly