Educational interventions in neurology:A comprehensive systematic review

A fear of neurology and neural sciences (neurophobia) may have clinical consequences. There is therefore a need to formulate an evidence-based approach to neurology education. A comprehensive systematic review of educational interventions in neurology was performed. BEI, Cochrane Library, Dialog Datastar, EBSCO Biomedical, EBSCO Psychology & Behavioral Sciences, EMBASE, ERIC, First Search, MDConsult, Medline, Proquest Medical Library and Web of Knowledge databases were searched for all published studies assessing interventions in neurology education among undergraduate students, junior medical doctors and residents up to and including July 2012. Two independent literature searches were performed for relevant studies, which were then classified for level of evidence using the Centre of Evidence-based Medicine criteria and four levels of Kirkpatrick educational outcomes. One systematic review, 16 randomized controlled trials (RCTs), nine non-randomized cohort/follow-up studies, 33 case series or historically controlled studies and three mechanism-based reasoning studies were identified. Educational interventions showed favourable evaluation or assessment outcomes in 15 of 16 (94%) RCTs. Very few studies measured subsequent clinical behaviour (two studies) and patient outcomes (one study). There is very little high quality evidence of demonstrably effective neurology education. However, RCTs are emerging, albeit without meeting comprehensive educational criteria. An improving evidence base in the quality of neurology education will be important to reduce neurophobia. © 2013 EFNS.

Session 4: CVD, diabetes and cancer - Evidence for the use of the Mediterranean diet in patients with CHD

Diet is associated with the development of CHD. The incidence of CHD is lower in southern European countries than in northern European countries and it has been proposed that this difference may be a result of diet. The traditional Mediterranean diet emphasises a high intake of fruits, vegetables, bread, other forms of cereals, potatoes, beans, nuts and seeds. It includes olive oil as a major fat source and dairy products, fish and poultry are consumed in low to moderate amounts. Many observational studies have shown that the Mediterranean diet is associated with reduced risk of CHD, and this result has been confirmed by meta-analysis, while a single randomised controlled trial, the Lyon Diet Heart study, has shown a reduction in CHD risk in subjects following the Mediterranean diet in the secondary prevention setting. However, it is uncertain whether the benefits of the Mediterranean diet are transferable to other non-Mediterranean populations and whether the effects of the Mediterranean diet will still be feasible in light of the changes in pharmacological therapy seen in patients with CHD since the Lyon Diet Heart study was conducted. Further randomised controlled trials are required and if the risk-reducing effect is confirmed then the best methods to effectively deliver this public health message worldwide need to be considered.

Neurophobia among general practice trainees: The evidence, perceived causes and solutions

Introduction

As general practice (GP) is the main source of referrals to neurologists, neurology education for GP trainees is important. We investigated the existence of neurophobia, contributing factors and potential prevention strategies among GP trainees.

In a questionnaire survey interest, knowledge, confidence and perceived difficulty in neurology were compared with different medical specialties. Reasons for difficulty with neurology, postgraduate neurology education experience, learning methods and suggested teaching improvements were examined.

Of 205 GP trainees, 118 (58%) completed the questionnaire. Threshold analyses justified categorical intervals for the Likert responses. Trainees recorded poorer knowledge (p < 0.001), less confidence (p < 0.001) and more perceived difficulty (p < 0.001) with neurology than with any other medical specialty. GP trainees had less interest in neurology than any other medical specialty (Duncan test, p < 0.001). There was a similar gradation in difficulty and confidence perception across medical specialties. Hospital and community-based neurology teaching was graded as “poor” or “very poor” by over 60% of GP trainees. There were multiple perceived causes of neurophobia, including neuroanatomy and poor quality teaching. More organised clinical teaching and referral guidance were suggested to address GP neurophobia.

Neurophobia is common among GP trainees in Northern Ireland. GP trainees have clear and largely uniform ideas on improving their neurology education. GP training posts should reflect the importance of neurology within the GP curriculum.

Energy compensation in the real world: Good compensation for small portions of chocolate and biscuits over short time periods in complicit consumers using commercially available foods

While investigations using covert food manipulations tend to suggest that individuals are poor at adjusting for previous energy intake, in the real world adults rarely consume foods of which they are ill-informed. This study investigated the impact in fully complicit consumers of consuming commercially available dark chocolate, milk chocolate, sweet biscuits and fruit bars on subsequent appetite. Using a repeated measures design, participants received four small portions (4 × 10-11 g) of either dark chocolate, milk chocolate, sweet biscuits, fruit bars or no food throughout five separate study days (counterbalanced in order), and test meal intake, hunger, liking and acceptability were measured. Participants consumed significantly less at lunch following dark chocolate, milk chocolate and sweet biscuits compared to no food (smallest t(19) = 2.47, p = 0.02), demonstrating very good energy compensation (269-334%). No effects were found for fruit bars (t(19) = 1.76, p = 0.09), in evening meal intakes (F(4,72) = 0.62, p = 0.65) or in total intake (lunch + evening meal + food portions) (F(4,72) = 0.40, p = 0.69). No differences between conditions were found in measures of hunger (largest F(4,76) = 1.26, p = 0.29), but fruit bars were significantly less familiar than all other foods (smallest t(19) = 3.14, p = 0.01). These findings demonstrate good compensation over the short term for small portions of familiar foods in complicit consumers. Findings are most plausibly explained as a result of participant awareness and cognitions, although the nature of these cognitions cannot be discerned from this study. These findings however, also suggest that covert manipulations may have limited transfer to real world scenarios.

In women, increased dietary antioxidants are associated with reduced risk of developing heart failure

Commentary on

Rautiainen S, Levitan EB, Mittleman MA, et al. Total antioxidant capacity of diet and risk of heart failure: a population-based prospective cohort of women. Am J Med 2013;126:494–500.

Patient safety and communication: A new assessment for doctors trained in countries where language differs from that of the host country: Results of a pilot using a domain-based assessment

Objective

Global migration of healthcare workers places responsibility on employers to comply with legal employment rights whilst ensuring patient safety remains the central goal. We describe the pilot of a communication assessment designed for doctors who trained and communicated with patients and colleagues in a different language from that of the host country. It is unique in assessing clinical communication without assessing knowledge.

A 14-station OSCE was developed using a domain-based marking scheme, covering professional communication and English language skills (speaking, listening, reading and writing) in routine, acute and emotionally challenging contexts, with patients, carers and healthcare teams. Candidates (n = 43), non-UK trained volunteers applying to the UK Foundation Programme, were provided with relevant station information prior to the exam.

The criteria for passing the test included achieving the pass score and passing 10 or more of the 14 stations. Of the 43 candidates, nine failed on the station criteria. Two failed the pass score and also the station criteria. The Cronbach's alpha coefficient was 0.866.

This pilot tested ‘proof of concept’ of a new domain-based communication assessment for non-UK trained doctors.

The test would enable employers and regulators to verify communication competence and safety in clinical contexts, independent of clinical knowledge, for doctors who trained in a language different from that of the host country.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Business Intelligence and Multi-market Competition

We consider a multi-market framework where a set of firms compete on two oligopolistic markets. The cost of production of each firm allows for spillovers across markets, ensuring that output decisions for both markets have to be made jointly. Prior to competing in these markets, firms can establish links gathering business intelligence about other firms. A link formed by a firm generates two types of externalities for competitors and consumers. We characterize the business intelligence equilibrium networks and networks that maximize social welfare. By contrast with single market competition, we show that in multi-market competition there exist situations where intelligence gathering activities are underdeveloped with regard to social welfare and should be tolerated, if not encouraged, by public authorities.

Internalization and desensitization of the human glucose-dependent-insulinotropic receptor is affected by N-terminal acetylation of the agonist

How incretins regulate presence of their receptors at the cell surface and their activity is of paramount importance for the development of therapeutic strategies targeting these receptors. We have studied internalization of the human Glucose-Insulinotropic Polypeptide receptor (GIPR). GIP stimulated rapid robust internalization of the GIPR, the major part being directed to lysosomes. GIPR internalization involved mainly clathrin-coated pits, AP-2 and dynamin. However, neither GIPR C-terminal region nor β-arrestin1/2 was required. Finally, N-acetyl-GIP recognized as a dipeptidyl-IV resistant analogue, fully stimulated cAMP production with a ∼15-fold lower potency than GIP and weakly stimulated GIPR internalization and desensitization of cAMP response. Furthermore, docking N-acetyl-GIP in the binding site of modelled GIPR showed slighter interactions with residues of helices 6 and 7 of GIPR compared to GIP. Therefore, incomplete or partial activity of N-acetyl-GIP on signaling involved in GIPR desensitization and internalization contributes to the enhanced incretin activity of this peptide.

Potentially harmful excipients in neonatal medicines: A pan-European observational study

Objectives We aimed to describe administration of eight potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to hospitalised neonates in Europe and to identify risk factors for exposure. Methods All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis. Results Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates were recorded. EOI were found in 638 (31%) prescriptions and were administered to 456 (63%) neonates through a relatively small number of products (n=142; 27%). Parabens, found in 71 (13%) products administered to 313 (43%) neonates, were used most frequently. EOI administration varied by geographical region, GA and route of administration. Geographical region remained a significant determinant of the use of parabens, polysorbate 80, propylene glycol and saccharin sodium after adjustment for the potential covariates including anatomical therapeutic chemical class of the active ingredient. Conclusions European neonates receive a number of potentially harmful pharmaceutical excipients. Regional differences in EOI administration suggest that EOI-free products are available and provide the potential for substitution to avoid side effects of some excipients.

EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients

BACKGROUND: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation.

METHODS: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response).

RESULTS: Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS.

CONCLUSION: This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.

Energy versus data integrity trade-offs in embedded high-density logic compatible dynamic memories

Current variation aware design methodologies, tuned for worst-case scenarios, are becoming increasingly pessimistic from the perspective of power and performance. A good example of such pessimism is setting the refresh rate of DRAMs according to the worst-case access statistics, thereby resulting in very frequent refresh cycles, which are responsible for the majority of the standby power consumption of these memories. However, such a high refresh rate may not be required, either due to extremely low probability of the actual occurrence of such a worst-case, or due to the inherent error resilient nature of many applications that can tolerate a certain number of potential failures. In this paper, we exploit and quantify the possibilities that exist in dynamic memory design by shifting to the so-called approximate computing paradigm in order to save power and enhance yield at no cost. The statistical characteristics of the retention time in dynamic memories were revealed by studying a fabricated 2kb CMOS compatible embedded DRAM (eDRAM) memory array based on gain-cells. Measurements show that up to 73% of the retention power can be saved by altering the refresh time and setting it such that a small number of failures is allowed. We show that these savings can be further increased by utilizing known circuit techniques, such as body biasing, which can help, not only in extending, but also in preferably shaping the retention time distribution. Our approach is one of the first attempts to access the data integrity and energy tradeoffs achieved in eDRAMs for utilizing them in error resilient applications and can prove helpful in the anticipated shift to approximate computing.