Molecular fingerprinting of principal neurons in the rodent hippocampus: A neuroinformatics approach.

Neurons are often classified by their morphological and molecular properties. The online knowledge base Hippocampome.org primarily defines neuron types from the rodent hippocampal formation based on their main neurotransmitter (glutamate or GABA) and the spatial distributions of their axons and dendrites. For each neuron type, this open-access resource reports any and all published information regarding the presence or absence of known molecular markers, including calcium-binding proteins, neuropeptides, receptors, channels, transcription factors, and other molecules of biomedical relevance. The resulting chemical profile is relatively sparse: even for the best studied neuron types, the expression or lack thereof of fewer than 70 molecules has been firmly established to date. The mouse genome-wide in situ hybridization mapping of the Allen Brain Atlas provides a wealth of data that, when appropriately analyzed, can substantially augment the molecular marker knowledge in Hippocampome.org. Here we focus on the principal cell layers of dentate gyrus (DG), CA3, CA2, and CA1, which together contain approximately 90% of hippocampal neurons. These four anatomical parcels are densely packed with somata of mostly excitatory projection neurons. Thus, gene expression data for those layers can be justifiably linked to the respective principal neuron types: granule cells in DG and pyramidal cells in CA3, CA2, and CA1. In order to enable consistent interpretation across genes and regions, we screened the whole-genome dataset against known molecular markers of those neuron types. The resulting threshold values allow over 6000 very-high confidence (>99.5%) expressed/not-expressed assignments, expanding the biochemical information content of Hippocampome.org more than five-fold. Many of these newly identified molecular markers are potential pharmacological targets for major neurological and psychiatric conditions. Furthermore, our approach yields reasonable expression/non-expression estimates for every single gene in each of these four neuron types with >90% average confidence, providing a considerably complete genetic characterization of hippocampal principal neurons.

Name-calling in the hippocampus (and beyond): coming to terms with neuron types and properties.

Widely spread naming inconsistencies in neuroscience pose a vexing obstacle to effective communication within and across areas of expertise. This problem is particularly acute when identifying neuron types and their properties. Hippocampome.org is a web-accessible neuroinformatics resource that organizes existing data about essential properties of all known neuron types in the rodent hippocampal formation. Hippocampome.org links evidence supporting the assignment of a property to a type with direct pointers to quotes and figures. Mining this knowledge from peer-reviewed reports reveals the troubling extent of terminological ambiguity and undefined terms. Examples span simple cases of using multiple synonyms and acronyms for the same molecular biomarkers (or other property) to more complex cases of neuronal naming. New publications often use different terms without mapping them to previous terms. As a result, neurons of the same type are assigned disparate names, while neurons of different types are bestowed the same name. Furthermore, non-unique properties are frequently used as names, and several neuron types are not named at all. In order to alleviate this nomenclature confusion regarding hippocampal neuron types and properties, we introduce a new functionality of Hippocampome.org: a fully searchable, curated catalog of human and machine-readable definitions, each linked to the corresponding neuron and property terms. Furthermore, we extend our robust approach to providing each neuron type with an informative name and unique identifier by mapping all encountered synonyms and homonyms.

Clinical decision-making augmented by simulation training: neural correlates demonstrated by functional imaging: a pilot study.

BACKGROUND: Investigation of the neuroanatomical basis of clinical decision-making, and whether this differs when students are trained via online training or simulation training, could provide valuable insight into the means by which simulation training might be beneficial. METHODS: The aim of this pilot prospective parallel group cohort study was to investigate the neural correlates of clinical decision-making, and to determine if simulation as opposed to online training influences these neural correlates. Twelve third-year medical students were randomized into two groups and received simulation-based or online-based training on anaphylaxis. This was followed by functional magnetic resonance imaging scanning to detect brain activation patterns while answering multiple choice questions (MCQs) related to anaphylaxis, and unrelated non-clinical (control) questions. Performance in the MCQs, salivary cortisol levels, heart rate, and arterial pressure were also measured. RESULTS: Comparing neural responses to clinical and non-clinical questions (in all participants), significant areas of activation were seen in the ventral anterior cingulate cortex and medial prefrontal cortex. These areas were activated in the online group when answering action-based questions related to their training, but not in the simulation group. The simulation group tended to react more quickly and accurately to clinical MCQs than the online group, but statistical significance was not reached. CONCLUSIONS: The activation areas seen could indicate increased stress when answering clinical questions compared with general non-clinical questions, and in the online group when answering action-based clinical questions. These findings suggest simulation training attenuates neural responses related to stress when making clinical decisions.

Errors during the preparation of drug infusions: a randomized controlled trial.

BACKGROUND: We investigated the extent and frequency of dose errors and treatment delays made as a consequence of preparing drug infusions at the bedside, rather than using pre-filled syringes. METHODS: Forty-eight nurses with critical care experience volunteered to take part in this randomized, blinded, controlled study conducted in the simulation centre of an urban hospital. They assisted in the management of a simulated patient with septic shock. Vasopressor infusions were prepared either by diluting concentrated drugs from ampoules or were provided in syringes pre-filled beforehand by an intensive care unit resident. RESULTS: The time taken for the infusion to be started and the final concentration of the drugs were measured. We also measured the concentration of infusions prepared by a pharmacist and a pharmaceutical company. Nurses took 156 s to start infusions when using pre-filled syringes compared with 276 s when preparing them de novo, a mean delay of 106 s [95% confidence interval (CI) 73-140 s, P<0.0001]. One infusion prepared from ampoules contained one-fifth of the expected concentration of epinephrine; another contained none at all. Medication errors were 17.0 times less likely when pre-filled syringes were used (95% CI 5.2-55.5), and infusions prepared by pharmacy and industry were significantly more likely to contain the expected concentration (P<0.001 for norepinephrine and P=0.001 for epinephrine). CONCLUSIONS: Providing drug infusions in syringes pre-filled by pharmacists or pharmaceutical companies would reduce medication errors and treatment delays, and improve patient safety. However, this approach would have substantial financial implications for healthcare providers, especially in less developed countries.

Retention of drug administration skills after intensive teaching.

We have identified deficiencies in medical students' drug administration skills, and we attempted to address them with interactive online teaching modules and simulated critical incident scenarios. Short-term improvements have been evident with this intensive effort, but medium-term retention of skills has not been measured. A drug administration lecture, an online module and a simulated emergency scenario were offered to final year clinical students. None of the teaching was compulsory but participation was recorded, along with students' simulator performances and marks in an objective structured practical examination 9 months later. A poor simulator score predicted a poor performance in the later examination. Participation in the simulated scenario only significantly improved examination scores when supplemented by online teaching (p = 0.002). Intensive drug administration teaching using an online module and high fidelity simulation improves drug administration skills in the medium term. Students found simulation much more engaging than online teaching.

Factors influencing doctors' ability to calculate drug doses correctly.

Doctors and medical students are more likely to make errors in drug dose calculations when the strengths of drug solutions are expressed as ratios or percentages. We have already described how a doctor's specialty influences their drug dose calculation skills, having surveyed almost 3000 doctors in an online survey. Better teaching of drug administration skills or reinforcement of existing skills would appear to be needed. We sought to identify doctors that might benefit particularly from such teaching by other means than specialty alone, by subjecting existing data to further analysis. Almost 3000 doctors subscribing to a UK-based internet content provider had participated in an online questionnaire concerning drug-dose calculation. Each doctor's score in the multiple choice questionnaire was cross referenced with demographic data obtained from the hosts of the original survey whilst maintaining anonymity. Newly and recently qualified doctors, and doctors working in the community, struggled most with the calculations (p < 0.0001). There were also highly significant differences in the performances of doctors from different medical schools (p < 0.0001). As a new training programme for junior doctors is being introduced in the UK; we recommend that drug administration skills are given a prominent place in the curriculum, and again call for the standardisation of ampoule labelling to mass concentration.

Peri-operative atrioventricular block as a result of chemotherapy with epirubicin and paclitaxel.

A 47-year-old woman presented for mastectomy and immediate latissimus dorsi flap reconstruction having been diagnosed with carcinoma of the breast 6 months previously. In the preceding months she had received neo-adjuvant chemotherapy with epirubicin, paclitaxel (Taxol) and cyclophosphamide. This had been apparently uncomplicated and she had maintained a remarkably high level of physical activity. She was found to be bradycardic at pre-operative assessment but had no cardiac symptoms. Second degree Mobitz type II atrioventricular block was diagnosed on electrocardiogram, and temporary transvenous ventricular pacing instituted in the peri-operative period. We discuss how evidence-based guidelines would not have been helpful in this case, and how chemotherapy can exhibit substantial cardiotoxicity that may develop over many years. We suggest that patients who have received chemotherapy at any time should have a pre-operative electrocardiogram even if they are asymptomatic.

The effect of additional teaching on medical students' drug administration skills in a simulated emergency scenario.

Medical students have difficulty calculating drug doses correctly, but better teaching improves their performance in written tests. We conducted a blinded, randomised, controlled trial to assess the benefit of online teaching on students' ability to administer drugs in a simulated critical incident scenario, during which they were scored on their ability to administer drugs in solution presented as a ratio (adrenaline) or percentage (lidocaine). Forty-eight final year medical students were invited to participate; 44 (92%) attended but only nine of the 20 students (45%) directed to the extra teaching viewed it. Nevertheless, the teaching module significantly improved the students' ability to calculate the correct volume of lidocaine (p = 0.005) and adrenaline (p = 0.0002), and benefited each student's overall performance (p = 0.0007). Drug administration error is a very major problem and few interventions are known to be effective. We show that focusing on better teaching at medical school may benefit patient safety.

Influence of improved teaching on medical students' acquisition and retention of drug administration skills.

BACKGROUND: Drug administration error is a major problem causing substantial morbidity and mortality worldwide. Lack of education about drug administration appears to be a causative factor. We devised an online teaching module for medical students and assessed its short- and long-term efficacy. METHODS: One hundred and thirty clinical medical students were invited to undertake additional, online, teaching about drug administration. Those participating were identified and the number of web pages viewed recorded. The students' knowledge retention was tested by means of drug administration questions incorporated into routine assessments and examinations over the next 6 months. Other indices of all students' performance were recorded to correct for confounding factors. RESULTS: Just over half (52%) responded to the invitation to participate. The amount of interest they showed in the teaching module correlated positively with their performance in questions about drug administration, although the latter waned over time. Surprisingly, correcting for students' general ability and keenness revealed that the less able students were most likely to undertake the teaching module. CONCLUSIONS: Additional online teaching about drug administration improves students' knowledge of the topic but clearly requires reinforcement; however, only about half the students took up the option. Medical students must acquire these fundamental skills, and online teaching can help. Medical educators must ensure that drug administration is taught formally to all students as part of the curriculum and must understand that it may require additional teaching.

Medication errors in anaesthesia and critical care.

There is an increasing recognition that medication errors are causing a substantial global public health problem, as many result in harm to patients and increased costs to health providers. However, study of medication error is hampered by difficulty with definitions, research methods and study populations. Few doctors are as involved in the process of prescribing, selecting, preparing and giving drugs as anaesthetists, whether their practice is based in the operating theatre, critical care or pain management. Anaesthesia is now safe and routine, yet anaesthetists are not immune from making medication errors and the consequences of their mistakes may be more serious than those of doctors in other specialties. Steps are being taken to determine the extent of the problem of medication error in anaesthesia. New technology, theories of human error and lessons learnt from the nuclear, petrochemical and aviation industries are being used to tackle the problem.

Integrated approaches to academic anaesthesia - the Cambridge experience.

There is mounting concern about the pressures experienced by University Departments of Anaesthesia, which, if lost, could threaten undergraduate peri-operative medicine teaching, development of critical appraisal skills among anaesthetists, and the future of coherent research programs. We have addressed these problems by establishing a foundation course in scientific methods and research techniques (the Cambridge SMART Course), complemented by competitive, fully funded, 12-month academic trainee attachments. Research conducted during academic attachments has been published and used to underpin substantive grant applications allowing work towards higher degrees. Following the attachment, a flexible scheme ensures safe reintroduction to clinical training. Research at consultant level is facilitated by encouraging applications for Clinician Scientist Fellowships, and by ensuring that the University Department champions, legitimises and validates the allocation of research time within the new consultant contract. We believe that these are important steps in safeguarding research and teaching in anaesthesia, critical care and peri-operative medicine.

A web-based system for teaching, assessment and examination of the undergraduate peri-operative medicine curriculum.

Today's students are generally computer literate and have high expectations of university information technology resources. Most United Kingdom medical schools now provide networked computers for learning, research, communication and accessing the worldwide web. We have exploited these advances to augment and improve the teaching of peri-operative medicine and anaesthesia to medical students in our university, who are taught in several hospitals over a wide geographical area. Course material such as departmental induction information, lecture notes and assessment sheets can be accessed online, contributing to the smooth running of the course. Streamed videos and simulations allow students to familiarise themselves with common practical procedures in advance. Development of a web-based end of course assessment has resulted in substantially less administration and bureaucracy for course organisers and proved to be a valuable research tool. Students' and teachers' opinions of the new course structure have been overwhelmingly positive.

Palliative surgery for acute bowel obstruction caused by Kaposi's sarcoma in a patient with AIDS.

Patients with human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) can present with acute abdominal surgical problems, either with intra-abdominal opportunistic infection as a result of their immunosuppression, or with associated malignancies. We report a 39-year-old man who developed intermittent nausea and vomiting, which was originally thought to be a side-effect of the chemotherapy he was receiving for facial Kaposi's sarcoma. However, he was found to have intraperitoneal Kaposi's sarcoma causing small bowel obstruction, which was successfully excised at laparotomy. There were no perioperative complications despite AIDS-related respiratory disease. The patient remained free of abdominal symptoms until his death. HIV infections or AIDS alone should not be contraindications to surgery for such problems, as careful patient selection can yield good results and significantly improve quality of life.