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Student and pre-registration pharmacist performance in a UK Prescribing Assessment’: room for improvement and need for curricular change Background Increasingly the global policy direction is for patient-facing pharmacist prescribers. The ‘UK Prescribing Safety Assessment’ (PSA) was developed for medical graduates to demonstrate prescribing competencies in relation to the safe and effective use of medicines. Objectives To determine PSA performance of final year undergraduate student pharmacists (year 4) and pre-registration pharmacy graduates (year 5) and explore their opinions on its suitability. Setting Scotland, UK Methods Final year undergraduates (n = 238) and pre-registration pharmacists (n = 167) were briefed and undertook the PSA. PSA questions were mapped to specific thematic areas with 30 questions over 60 min. Data was analysed using descriptive statistics. A questionnaire was completed to gauge opinions on appropriateness of the PSA. Main Outcome Measure PSA scores Results Mean total PSA score for pre-registration pharmacists (64.4, SD 10) was significantly higher than for undergraduates (51.2, SD 12.0,) (p < 0.001). Pre-registration pharmacists performed significantly better across all question areas (all p < 0.001 other than ‘adverse drug reactions’, p < 0.01). Hospital pre-registration pharmacists performed statistically significantly better than community with higher overall scores (67.4, SD 9.8 v 63.2, SD 9.8, p < 0.05). Positive views on the appropriateness of the approach and the usability of the online interface were obtained from participants. Conclusion Hospital pre-registration pharmacists performed better than the undergraduates, but there is a need to improve prescribing skills in all, most notably in diagnostic skills. The PSA is acceptable to the participants. These results will help inform pharmacy curricula development and provides a cross-disciplinary method of assessment of prescribing competence.

Medical education has historically relied on high stakes knowledge tests sat in examination centres with invigilators monitoring academic malpractice. The COVID-19 pandemic has made such examination formats impossible, and medical educators have explored the use of online assessments as a potential replacement. This shift has in turn led to fears that the change in format or academic malpractice might lead to considerably higher attainment scores on online assessment with no underlying improvement in student competence.Here, we present an analysis of 8092 sittings of the Prescribing Safety Assessment (PSA), an assessment designed to test the prescribing skills of final year medical students in the UK. In-person assessments for the PSA were cancelled partway through the academic year 2020, with 6048 sittings delivered in an offline, traditionally invigilated format, and then 2044 sittings delivered in an online, webcam invigilated format.A comparison (able to detect very small effects) showed no attainment gap between online (The finding suggests that the transition to online assessment does not affect student performance. The findings should increase confidence in the use of online testing in high-stakes assessment.

AIMS Candidates with disabilities are eligible for reasonable adjustments (RA) while undertaking the national Prescribing Safety Assessment (PSA). The PSA is a novel open-book, time-constrained, multiformat assessment that may pose challenges to candidates with dyslexia and other disabilities. METHODS Retrospective cohort analysis of 36 140 UK candidates undertaking first-sitting of the PSA (2014-2018). RESULTS Of the 36 140 candidates, 9.1% (3284) were registered for RA. The RA group had lower pass rates (absolute difference 1.94%, 95% confidence interval 1.01-2.87%; P < .001) and assessment scores (1.16 percentage marks, 95% confidence interval 0.83-1.48; P < .001) compared with the non-RA group. This absolute difference is small relative to overall variability. This difference persists after adjusting for confounding factors (medical school and paper), and was present for all 8 different question types. The attainment gap within each medical school is negatively correlated with the school's overall performance, both in terms of pass rate (P < .001) and scores (P = .01). The RA group were also less likely to perceive the PSA as an appropriate test, having easy to follow layout/presentation or clear/unambiguous questions, even after adjusting for candidate performance. CONCLUSION This analysis identifies slight differences in academic performance of candidates requiring RA in a national undergraduate assessment. The study is limited by the unavailability of data on ethnicity, sex, age, diagnosis and time of diagnosis. While further research is required to determine the cause of the attainment gap, this study emphasises the need to maintain a careful review on the fairness and validity of all aspects of the assessment.

All retroviruses encode a Gag polyprotein containing an N-terminal matrix domain (MA) that anchors Gag to the plasma membrane and recruits envelope glycoproteins to virus assembly sites. Membrane binding by the Gag protein of HIV-1 and most other lentiviruses is dependent on N-terminal myristoylation of MA by host Nmyristoyltransferase enzymes (NMTs), which recognize a six-residue “myristoylation signal” with consensus sequence: M(1)GXXX[ST]. For unknown reasons, the feline immunodeficiency virus (FIV), which infects both domestic and wild cats, encodes a non-consensus myristoylation sequence not utilized by its host or by other mammals (most commonly: M(1)GNGQG). To explore the evolutionary basis for this sequence, we compared the structure, dynamics, and myristoylation properties of native FIV MA with a mutant protein containing a consensus feline myristoylation motif (MA(NOS)) and examined the impact of MA mutations on virus assembly and ability to support spreading infection. Unexpectedly, myristoylation efficiency of MA(NOS) in E. coli by co-expressed mammalian NMT was reduced by ~70% compared to the wild-type protein. NMR studies revealed that residues of the N-terminal myristoylation signal are fully exposed and mobile in the native protein but partially sequestered in the MA(NOS) chimera, suggesting that the unusual FIV sequence is conserved to promote exposure and efficient myristoylation of the MA N-terminus. In contrast, virus assembly studies indicate that the MA(NOS) mutation does not affect virus assembly, but does prevent virus spread, in feline kidney cells. Our findings indicate that residues of the FIV myristoylation sequence play roles in replication beyond NMT recognition and Gag–membrane binding.

Aims To identify and evaluate clinical pharmacology (CP) online curricular (e-Learning) resources that are internationally available for medical students. Methods Literature searches of Medline, EMBASE and ERIC databases and an online survey of faculty members of international English language medical schools, were used to identify CP e-Learning resources. Resources that were accessible online in English and aimed to improve the quality of prescribing specific medications were then evaluated using a summary percentage score for comprehensiveness, usability and quality, and for content suitability. Results Our literature searches and survey of 252 faculty (40.7% response rate) in 219 medical schools identified 22 and 59 resources respectively. After screening and removing duplicates, 8 eligible resources remained for evaluation. Mean total score was 53% (standard deviation = 13). The Australian National Prescribing Curriculum, ranked highest with a score of 77%, based primarily on very good ratings for usability, quality and suitable content. Conclusion Using a novel method and evaluation metric to identify, classify, and rate English language CP e-Learning resources, the National Prescribing Curriculum was the highest ranked open access resource. Future work is required to implement and evaluate its effectiveness on prescribing competence.

BackgroundIncreasingly the global policy direction is for patient-facing pharmacist prescribers. The ‘UK Prescribing Safety Assessment’ (PSA) was developed for medical graduates to demonstrate prescribing competencies in relation to the safe and effective use of medicines.ObjectivesTo determine PSA performance of final year undergraduate student pharmacists (year 4) and pre-registration pharmacy graduates (year 5) and explore their opinions on its suitability. SettingScotland, UKMethodsFinal year undergraduates (n= 238) and pharmacy pre-registration graduates (n= 167) were briefed and undertook the PSA. PSA questions were mapped to specific thematic areas with 30 questions over 60 minutes. Data was analysed using descriptive statistics. A questionnaire was completed to gauge opinions on appropriateness of the PSA.Main Outcome Measure PSA scoresResultsMean total PSA score for pre-registration graduates (64.4, SD 10) was significantly higher than for undergraduates (51.2, SD 12.0,) (pConclusionHospital graduates performed better than the undergraduates, but there is a need to improve prescribing skills in all, most notably in diagnostic skills. The PSA is acceptable to the participants. These results will help inform pharmacy curricula development and provides a cross-disciplinary method of assessment of prescribing competence.

Online learning, an essential component of most traditional contact-based educational programs, must be of high quality to contribute effectively to learning. The availability of first-class web-based materials is particularly valued by both learners and educators in resource-poor nations. In this Practice article, we introduce the International Union of Basic and Clinical Pharmacology (IUPHAR) Pharmacology Education Project (PEP) (https://www.pharmacologyeducation.org/), a freely accessible online learning resource intended to support education and training in pharmacological sciences worldwide.

Background Prescribing is a complex task requiring considerable knowledge and skills. The Prescribing Safety Assessment (PSA) was developed by the British Pharmacological Society and the United Kingdom (UK) Medical Schools Council. Between February and June 2014, over 7000 final year medical students undertook the PSA, with an overall pass rate of 94%. Independent prescribing for suitably trained pharmacists was introduced in the UK in 2006. To date there has been little focus on any objective measures of prescribing safety. Objective To determine the PSA performance of a pilot group of pharmacist prescribers in Scotland relative to medical students and to test the feasibility and acceptability of running the PSA. Methods: A group of 59 pharmacist prescribers took part in ten events. The PSA consisted of 30 questions to be completed over 60 min. All questions had been used in the 2014 assessments for final year medical students. The PSA was undertaken online under invigilated conditions, mirroring the medical student assessment. One month later, participants were invited to complete an online evaluation questionnaire. Results The mean overall PSA scores (±SD) were 87.5% ± 8.7 (range 52–98) compared to a 88.5% for medical students. Based on an Angoff passmark of 76.0%, 53 pharmacists (89.8%) passed compared to an overall pass rate in PSA 2014 of 94%. Pharmacists performed equivalently to medical students in all assessment areas, with a slightly lower performance in the prescribing, drug monitoring and data interpretation questions offset by better performance in prescription review and adverse drug reactions. Feedback was positive in relation to appropriateness, relevance and level of difficulty of the PSA although several commented that they were practicing in very specific clinical areas. Conclusion These pilot events have benchmarked the PSA performance of pharmacist prescribers with final year medical students, and feedback confirmed feasibility and acceptability.

The past decade of political failure on climate change has cost us all dear. It has shrunk the time left for action by two-thirds. In 2010, the world thought it had 30 years to halve global emissions of greenhouse gases. Today, we know that this must happen in ten years to minimize the effects of climate change. Incremental shifts that might once have been sufficient are no longer enough.

Background This paper seeks to contribute to a reputable evidence base for required competencies across different topics in statistics and probability (statistical topics) in preparing medical graduates for clinical practice. This is in order to inform the prioritization of statistical topics within future undergraduate medical curricula, while exploring the need for preparing tomorrow’s doctors to be producers, and not merely consumers, of statistics. Methods We conducted a comprehensive online survey from July 2013 to August 2014 for a target group of 462 medical graduates with current or prior experience of teaching undergraduate medical students of the University of Edinburgh of whom 278 (60.2%) responded. Statistical topics were ranked by proportion of respondents who identified the practice of statistics, performing statistical procedures or calculations using appropriate data, as a required competency for medical schools to provide in preparing undergraduate medical students for clinical practice. Mixed effects analyses were used to identify potential predictors for selection of the above competency and to compare the likelihood of this selection for a range of statistical topics versus critical appraisal. Results Evidence was gleaned from medical graduates’ experiences of clinical practice for the need for, not only a theoretical understanding of statistics and probability but also, the ability to practice statistics. Nature of employment and statistical topic were highly significant predictors of choice of the practice of statistics as a required competency ((F = 3.777, p Conclusions The model of medical graduates as mere consumers of statistics is oversimplified. Contrary to what has been suggested elsewhere, statistical learning opportunities in undergraduate medicine should not be restricted to development of critical appraisal skills. Indeed, our findings support development of learning opportunities for undergraduate medical students as producers of statistics across a wide range of statistical topics.

Introduction Medical textbooks are an important teaching supplement. Few have junior doctors or medical students (‘juniors’) as primary contributors. However, the strengths of junior-led face-to-face teaching are now well-established, and we hypothesized that similar advantages would be transferrable to a textbook setting. Methods Juniors were approached to contribute to an independently published medical textbook, with senior clinicians recruited in parallel to ensure factual accuracy. Juniors directed every aspect of textbook writing and the production process. The published book stressed that it was an open collaboration with readers, inviting them to get in touch to evaluate the text and suggest ideas for new titles. Results Of 75 respondents, 93 % awarded the first textbook in the series 4 or 5 out of 5 for overall quality. Five other titles have been released, with seven more in development. Over 100 juniors are currently involved, with two students progressing from reviewers to editors after less than a year of mentorship. Conclusion Juniors can be a motivated, dynamic, innovative group, capable of significant contributions to the medical textbook literature. This initiative has generated a sustainable infrastructure to facilitate junior-led publishing, and has the capacity for expansion to accommodate new initiatives and ideas.

Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery, and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students' preparedness for prescribing. In all, 185 medical schools (64%) from 27 EU countries responded. Traditional learning methods were mainly used. The majority of respondents did not provide students with the opportunity to practice real-life prescribing and believed that their students were not well prepared for prescribing. There is a marked difference in the quality and quantity of CPT education within and between EU countries, suggesting that there is considerable scope for improvement. A collaborative approach should be adopted to harmonize and modernize the undergraduate CPT education across the EU.

Medical textbooks remain an integral component of the undergraduate education pathway. These texts are traditionally prepared by senior clinicians or academics, based on their long experience of the subject matter. Medical students and junior doctors are commonly asked to review these books, but often have little role in influencing the content. This article will discuss the opening of a new paradigm in medical publishing, whereby students and junior doctors (juniors) take the lead in planning and producing the content of their textbooks with senior clinicians taking the role of reviewer.

Junior doctors write the majority of hospital prescriptions but many indicate they feel underprepared to assume this responsibility and around 10% of prescriptions contain errors. Medical smartphone apps are now widely used in clinical practice and present an opportunity to provide support to inexperienced prescribers. This study assesses the contemporary range of smartphone apps with prescribing or related content. Six smartphone app stores were searched for apps aimed at the healthcare professional with drug, pharmacology or prescribing content. Three hundred and six apps were identified. 34% appeared to be for use within the clinical environment in order to aid prescribing, 14% out with the clinical setting and 51% of apps were deemed appropriate for both clinical and non-clinical use. Apps with drug reference material, such as textbooks, manuals or medical apps with drug information were the commonest apps found (51%), followed by apps offering drug or infusion rate dose calculation (26%). 68% of apps charged for download, with a mean price of £14.25 per app and a range of £0.62–101.90. A diverse range of pharmacology-themed apps are available and there is further potential for the development of contemporary apps to improve prescribing performance. Personalized app stores may help universities/healthcare organizations offer high quality apps to students to aid in pharmacology education. Users of prescribing apps must be aware of the lack of information regarding the medical expertise of app developers. This will enable them to make informed choices about the use of such apps in their clinical practice.

Aims Prescribing errors are common and inadequate preparation of prescribers appears to contribute. A junior doctor-led prescribing tutorial programme has been developed for Edinburgh final year medical students to increase exposure to common prescribing tasks. The aim of this study was to assess the impact of these tutorials on students and tutors. Methods One hundred and ninety-six tutorials were delivered to 183 students during 2010–2011. Each student completed a questionnaire after tutorial attendance which explored their previous prescribing experiences and the perceived benefits of tutorial attendance. Tutors completed a questionnaire which evaluated their teaching experiences and the impact on their prescribing practice. Student tutorial attendance was compared with end-of-year examination performance using linear regression analysis. Results The students reported increased confidence in their prescribing knowledge and skills after attending tutorials. Students who attended more tutorials also tended to perform better in end-of-year examinations (Drug prescribing: r = 0.16, P = 0.015; Fluid prescribing: r = 0.18, P = 0.007). Tutors considered that participation enhanced their own prescribing knowledge and skills. Although they were occasionally unable to address student uncertainties, 80% of tutors reported frequently correcting misconceptions and deficits in student knowledge. Ninety-five percent of students expressed a preference for prescribing training delivered by junior doctors over more senior doctors. Conclusions A ‘near-peer’ junior doctor-led approach to delivering prescribing training to medical students was highly valued by both students and tutors. Although junior doctors have relatively less clinical experience of prescribing, we believe that this can be addressed by training and academic supervision and is outweighed by the benefits of these tutorials.

Aims The aim of the study was to explore and compare junior doctors' perceptions of their self-efficacy in prescribing, their prescribing errors and the possible causes of those errors.

Prescribing is one of the commonest tasks expected of new doctors and is a complex process involving a mixture of knowledge, judgement and skills. Preparing graduates to be prescribers is one of the greatest challenges of modern undergraduate medical education and there is some evidence to suggest that training could be improved. The aims of this article are (i) to review some of the challenges of delivering effective prescribing education, (ii) to provide a clear statement of the learning outcomes in clinical pharmacology and prescribing that should be expected of all medical graduates and (iii) to describe a curriculum that might enable students to achieve these outcomes. We build on the previous curriculum recommendations of the British Pharmacological Society and take into account those of other key bodies, notably the General Medical Council. We have also reviewed relevant evidence from the literature and set our work in the context of recent trends in medical education. We divide our recommended learning objectives into four sections: principles of clinical pharmacology, essential drugs, essential therapeutic problems and prescribing skills. Although these will not necessarily be accepted universally we believe that they will help those who design and map undergraduate curricula to explore potential gaps and identify improvements.

Preparing medical students to prescribe is a major challenge of undergraduate education. They must develop an understanding of clinical pharmacology and acquire knowledge about drugs and therapeutics, as well as the skills to prescribe for individual patients in the face of multiple variables. The task of delivering the learning required to achieve these attributes relies upon limited numbers of teachers, who have increasingly busy clinical commitments. There is evidence that training is currently insufficient to meet the demands of the workplace. e-Learning provides an opportunity to improve the learning experience. The advantages for teachers are improved distribution of learning content, ease of update, standardization and tracking of learner activities. The advantages for learners are ease of access, greater interactivity and individual choice concerning the pace and mix of learning. Important disadvantages are the considerable resource required to develop e-Learning projects and difficulties in simulating some aspects of the real world prescribing experience. Pre-requisites for developing an e-Learning programme to support prescribing include academic expertise, institutional support, learning technology services and an effective virtual learning environment. e-Learning content might range from complex interactive learning sessions through to static web pages with links. It is now possible to simulate and provide feedback on prescribing decisions and this will improve with advances in virtual reality. Other content might include a student formulary, self-assessment exercises (e.g. calculations), a glossary and an on-line library. There is some evidence for the effectiveness of e-Learning but better research is required into its potential impact on prescribing.

Prescribing of medicines is the key clinical activity in the working life of most doctors. In recent years, a broad consensus regarding the necessary competencies has been achieved. Each of these is a complex mix of knowledge, judgement and skills. Surveys of those on the threshold of their medical careers have revealed widespread lack of confidence in writing prescriptions. A valid and reliable assessment of prescribing competence, separate from an overall assessment of medical knowledge and skill, would have many benefits for clinical governance and patient safety, and would provide a measure of the success of training programmes in therapeutics. Delivering such an assessment presents many challenges, not least of which are the difficulty in identifying a surrogate marker for competent prescribing in clinical practice and the challenge of ensuring that competence assessed in a controlled environment predicts performance in clinical practice. This review makes the case for an on-line OSCE as the most valid form of assessment and sets out the requirements for its development, scope, composition and delivery. It describes an on-going attempt to develop a national assessment of prescribing skills towards the end of undergraduate medical training in the UK.

Clinical pharmacology and therapeutics is the academic discipline that informs rational prescribing of medicines. There is accumulating evidence that a significant minority of prescriptions in the UK National Health Service contain errors. This comes at a time when the approach to and success of undergraduate education in this area has been called into question. Various stakeholders are now in agreement that this challenging area of undergraduate education needs to be strengthened. The principles that should form the basis of future educational strategy include greater visibility of clinical pharmacology and therapeutics in the curriculum, clear learning outcomes that are consistent with national guidance, strong and enthusiastic leadership, a student formulary, opportunities to practice prescribing, a robust assessment of prescribing competencies and external quality control. Important new developments in the UK are Prescribe, a repository of e-learning materials to support education in clinical pharmacology and prescribing, and the Prescribing Skills Assessment, a national online assessment designed to allow medical students to demonstrate that they have achieved the core competencies required to begin postgraduate training.

Prescribing medicines safely and effectively represents one of the greatest challenges for healthcare systems. Prescribing errors are common. A recent prospective observational study in the UK suggested that 10% of hospital prescriptions contained errors and that senior doctors were almost as frequently culpable as those who had recently graduated [1]. Avoidable adverse drug reactions are a frequent cause of consultations in primary care, admission to hospital and increased length of hospital stay [2, 3]. All healthcare providers should be striving to provide high-quality prescribing that meets the goals of being safe, effective, cost-effective and patient-centred [4]. The reasons for this failure to deliver these optimal standards of care are multiple but can be broadly divided into those that surround individuals, such as education and training and those that relate to the systems in which they work. The healthcare environment is now increasingly demanding for prescribers because of the widening choice of medicines available, expanding indications for drug treatment, greater complexity of treatment regimens and associated ‘polypharmacy’, and a more elderly and vulnerable patient cohort. The other major challenge is the pace of change in therapeutics. New evidence on effectiveness, emerging safety signals and altered costs means that what is considered good prescribing today may not necessarily be so in a year. Amidst all of these pressures it is now clear that the mid-20th century model of training prescribers in medical school and providing them with books of reference information (e.g. national or local formularies) is no longer fit for purpose. The modern day prescriber will need electronic drug information that is instantly available and in a logical format that can interface with the electronic health record and decision support systems. Bringing these three developments together has the potential to help prescribers to improve selection and dosage of drugs, make better predictions of adverse effects and interactions and will also help patients to engage more fully in the process of selecting and monitoring their own treatment. However, there is plenty of evidence to suggest that delivery of information could be improved [5, 6]. A recent report of healthcare in six European member states (Czech Republic, France, the Netherlands, Sweden, Spain and the UK) estimated that about 100 000 inpatient adverse drug events could be avoided each year in the six member states by implementing better electronic drug services [5]. This would correspond to an annual saving of €300m in bed days. The potential for improved information technology to save money and advance important political objectives such as patient safety, healthcare access and continuity of care should accelerate our efforts to develop new and user-friendly sources of drug information. So what might a new electronic system look like? It will involve several important elements including an electronic health record (EHR), a computerized physician order entry system (CPOE) and a highly developed decision support system (DSS). Each of these elements will have to be underpinned by access to an authoritative, standardized, validated and regularly updated repository of information about prescribed drugs (dosages, packages and mode of administration; Figure 1). Although many parts of the electronic prescribing vision are already in place there is still a lack of standardized electronic drug information (EDI) that can be integrated easily into DSS and EHRs. The need for standardized formats of structure, storage, visualization and communication of drug information has been highlighted in various reports [6, 7]. Figure 1 The e-SPC structure with data content can be co-ordinated with other data sources and knowledge databases, as well as electronic health records (EHR) and decision support systems (DSS), to implement a new model of electronically supported prescribing. ... How can EDI be developed? The European Medicine Agency (or the national regulatory bodies) currently require the manufacturers of all medicines to provide a summary of product characteristics (SPC) prior to the granting of a market authorization. The SPC contains detailed information about the medicinal product accumulated during the development process and regularly updated after approval and can help health professionals to use the medicinal product safely and effectively. The current SPC is a chapter-based document available only as plain free text. Each is available as a single document file and is published in portable document format running typically to between 10 and 30 pages. Its length and the fragmentation of information make them time-consuming to read and data hard to retrieve. Prescribers simply do not have the time to consult them as they make rapid ‘point of care’ decisions in clinical practice [8, 9]. Although this information provides support for health professionals as they initiate and supervise treatment safely and effectively, it falls short of the standardization and detail required to make accurate predictions on outcome. For example, adverse effects of medicines need to be described in standard terms and grouped according to frequency and body system that they affect. Dosing decisions require detailed information about pharmacokinetics in different groups of patients and drug indications should be described with specific diagnostic codes for easy linkage to patient data in EHRs. These problems emphasize the need for a detailed and carefully structured SPC that is available in a logical electronic format (e-SPC) that can complement the increasingly detailed information available in EHRs (e.g. past diseases and care episodes, current and past medicines, physiological and biochemical data). A major challenge is that a new e-SPC that offers relevant data to support complex decisions regarding, e.g. dose selection, will require information about parameters that are currently not available (or only incompletely) at the time of marketing. For example, the current SPC gives insufficient details to allow prescribers to make common dose adjustments necessitated by factors such as renal impairment or drug interactions [10, 11] and variations in pharmacokinetics are not well supported [12, 13]. Providing these details will involve not only pre-licensing studies but also careful accumulation of relevant data in the post-marketing phase. This will have to focus more clearly on parameters that will be of importance to patients who will be exposed to the drug, doctors who prescribe it and those who administer the drugs. The primary focus of future efforts with improved drug information should be to support prescribers and patients but the new e-SPC could also help other groups. These might include: (i) drug companies or clinical researchers during pre- and post-registration clinical drug development; (ii) clinical researchers who wish to combine existing EHRs with the results of prospective clinical trials to understand better how drugs produce their beneficial and adverse effects; and (iii) pharmacoepidemiologists who wish to understand safety signals derived from observational studies in large linked data sets. All of these groups would have access to carefully structured and predictable information that could be integrated into their own data sets. There will be many hurdles to overcome before rolling out the new era of EDI. The new e-SPC format needs to be specified and this will require agreement between stakeholders in the pharmaceutical industry, the regulators and healthcare providers. Another important stakeholder will be those who develop CPOE and DSS systems with which e-SPC would have to integrate. There will need to be an effective education package created, together with guidelines for use in other software systems across European healthcare institutions. It will be a major task to convert all, or even a subset of, the existing SPCs to the new format. While we strongly support the utilization of new technology to deliver extra layers of safety to the complex task of prescribing, we also readily acknowledge that such systems offer the potential to introduce new kinds of hazards [14, 15]. The introduction of CPOE and DSS systems requires close monitoring to identify potential flaws [16] and unanticipated clinical risk situations [15]. Nevertheless, prescribing-related errors and harm are so common that we should address these new challenges and not lose sight of the potential gains that the new electronic prescribing era will offer [17]. Notwithstanding all of these challenges it is clear that structured and standardized electronic drug information that can be easily accessed is vital for future clinical drug development, clinical drug research and for improving the prescribing decisions that are made at the point of patient care across Europe. Such a development will also help to enhance overall efficiency in the use of healthcare resources and will establish drug information standards that will benefit development of medical guidelines and knowledge bases by medical professional organizations and universities [18]. This development will not happen without the input of considerable effort and resource at a time when budgets are tight. However, looking at the costs currently imposed by suboptimal use of medicines in Europe the question should not be ‘Can we afford to do this?’ but rather ‘Can we afford NOT to do this?’.

AIMS Relevant and easily accessible drug information at point-of-care is essential for physicians' decision making when prescribing. However, the information available by using Clinical Decision Support Systems (CDSSs) often does not meet physicians' requirements. The Summary of Product Characteristics (SmPC) is statutory information about drugs. However, the current structure, content and format of SmPCs make it difficult to incorporate them into CDSSs and link them to relevant patient information from the Electronic Health Records. The aim of the study was to evaluate the perceived needs for drug information among physicians in Sweden. METHODS We recruited three focus group discussions with 18 physicians covering different specialities. The information from the groups was combined with a questionnaire administered at the beginning of the group discussions. RESULTS Physicians reported their needs for knowledge databases at the point of drug prescribing. This included more consistent information about existing and new drugs. They also wished to receive automatically generated alerts for severe drug-drug interactions and adverse effects, and to have functions for calculating glomerular filtration rate to enable appropriate dose adjustments to be made for elderly patients and those with impaired renal function. Additionally, features enhancing electronic communication with colleagues and making drug information more searchable were suggested. CONCLUSIONS The results from the current study showed the need for knowledge databases which provide consistent information about new and existing drugs. Most of the required information from physicians appeared to be possible to transfer from current SmPCs to CDSSs. However, inconsistencies in the SmPC information have to be reduced to enhance their utility.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Dose calculation errors are an important cause of some of the most serious medication incidents in advanced healthcare systems. • A number of small studies have shown that dose calculations are poorly performed by hospital doctors, nurses and medical students. WHAT THIS PAPER ADDS • The performance of dose calculations was highly variable amongst a large cohort of medical students from a leading UK medical school. • Calculations that involved converting concentrations expressed as percentage or calculating infusion rates were identified as major weaknesses. • The availability of an online self-assessment and education package, coupled with encouragement and twice-yearly formative assessment, led to a significant improvement in performance. AIMS Dose calculation errors can cause serious life-threatening clinical incidents. We designed eDrugCalc as an online self-assessment tool to develop and evaluate calculation skills among medical students. METHODS We undertook a prospective uncontrolled study involving 1727 medical students in years 1–5 at the University of Edinburgh. Students had continuous access to eDrugCalc and were encouraged to practise. Voluntary self-assessment was undertaken by answering the 20 questions on six occasions over 30 months. Questions remained fixed but numerical variables changed so each visit required a fresh calculation. Feedback was provided following each answer. RESULTS Final-year students had a significantly higher mean score in test 6 compared with test 1 [16.6, 95% confidence interval (CI) 16.2, 17.0 vs. 12.6, 95% CI 11.9, 13.4; n= 173, P < 0.0001 Wilcoxon matched pairs test] and made a median of three vs. seven errors. Performance was highly variable in all tests with 2.7% of final-year students scoring < 10/20 in test 6. Graduating students in 2009 (30 months' exposure) achieved significantly better scores than those in 2007 (only 6 months): mean 16.5, 95% CI 16.0, 17.0, n= 184 vs. 15.1, 95% CI 14.5, 15.6, n= 187; P < 0.0001, Mann–Whitney test. Calculations based on percentage concentrations and infusion rates were poorly performed. Feedback showed that eDrugCalc increased confidence in calculating doses and was highly rated as a learning tool. CONCLUSIONS Medical student performance of dose calculations improved significantly after repeated exposure to an online formative dose-calculation package and encouragement to develop their numeracy. Further research is required to establish whether eDrugCalc reduces calculation errors made in clinical practice.

Junior doctors feel poorly prepared by their training in Clinical Pharmacology and Therapeutics and commonly make prescribing errors. Since 1993 the General Medical Council's guidance on undergraduate medical education 'Tomorrow's Doctors' has emphasized the integration of Clinical Pharmacology and Therapeutics teaching within the medical curriculum. With the publication of a new version of Tomorrow's Doctors in 2009, medical schools will be further revising their Clinical Pharmacology and Therapeutics teaching. WHAT THIS STUDY ADDS Although we know what the recommendations for undergraduate teaching of Clinical Pharmacology and Therapeutics teaching are, there are no published data describing what is currently happening in UK medical schools. This paper describes the course structures, volume and range of teaching and assessment of Clinical Pharmacology and Therapeutics in the UK in 2009. Our data provide a foundation for schools looking to revise the Clinical Pharmacology and Therapeutics Teaching in the light of Tomorrow's Doctors 2009. AIM To describe the current structure, delivery and assessment of Clinical Pharmacology and Therapeutics (CPT) teaching in UK medical schools. METHODS An online questionnaire was distributed to the person with overall responsibility for CPT teaching at all UK medical schools in June 2009. RESULTS Thirty of the 32 UK medical schools responded. 60% of schools have a CPT course although in 72% this was an integrated vertical theme. At 70% of schools pharmacologists have overall responsibility for CPT teaching (clinical 67%, non-clinical 33%); at 20% teaching is run by a non-specialist clinician and at 7% by a pharmacist. Teaching is commonly delivered by NHS clinicians (87%) and clinical pharmacists (80%) using lectures (90%) but additionally 50% of schools use e-Learning and 63% have a student formulary. CPT is assessed throughout the curriculum at many schools through written, practical examinations and course work. 90% of schools have specific CPT content in their written examinations. 90% of respondents believed that their students were 'fairly' to 'well' prepared for the foundation year but only 37% of schools gather data on the competence of their graduates. CONCLUSIONS CPT teaching in UK medical schools is very diverse. Most schools do not assess the performance of their graduates as prescribers and there is a lack of evidence that many of the teaching approaches employed are suitable for the development of prescribing skills. It is vital that developments in CPT teaching are driven by validated, real-world assessments of the prescribing skills of medical students and newly qualified doctors.

Prescribing is the most important tool used by physicians to cure illness, relieve symptoms and prevent future disease. It is also a complex intellectual task that requires formulation of an appropriate treatment regimen from the many thousands available, taking into account the infinite variation in the patients they encounter. Unfortunately, the selection of a medicine and dosage regimen is sometimes suboptimal, leading to poor patient outcomes (eg treatment failure, avoidable adverse reactions). This article will highlight some of the common prescribing errors and will develop a rational approach that includes making a diagnosis, estimating prognosis, establishing the goals of therapy, selecting the most appropriate treatment and monitoring the effects of the treatment.

This paper stresses the difficulty of resolving the many debates on food aid without closer attention to the impact of food aid programmes. It argues, however, that inadequate, casual, ex‐post evaluation must be replaced by a comprehensive impact assessment system. The data requirements of such a system are explored for different sorts of food aid activity and ways of simplifying the monitoring and evaluation task are discussed, based on selectivity, a step by step approach and the use of data‐economising methods. Specific proposals are made for an international initiative on impact assessment, with donor coordination and a strengthening of indigenous capability in recipient countries.

RESUMENLos temas de la cosecha y post-cosecha en la investigacion de sistemas agricoles La creciente literatura sobre la investigacion de sistemas agricolas presta poca atencion al sistema de cosecha y post-cosecha (SCPC), Y aun asi el SCPC es probable que sea central en cualquier programa de investigacion de sistemas agricolas, tanto por ser prioritario de por si como por los efectos que tendran en el SCPC tradicional los cambios tecnologicos en otras partes del sistema agricola. El argumento se ilustra con un caso estudiado en Santa Cruz, Bolivia, examinandose asimismo las implicaciones para la organizacion de la investigacion de sistemas agricolas. SUMMARY The growing literature on farming systems research pays little attention to the harvest and post-harvest system (HPHS). Yet the HPHS is likely to be central to any programme of farming systems research both because it is a priority on its own account and because technology changes in other parts of the farm system disturb the traditional HPHS. The argument is illustrated by a case study from Santa Cruz, Bolivia and the implications for the organisation of farming systems research are examined. RESUMEQuestions de recoltes et post-recoltes dans la recherche des systemes agricoles La litterature grossisante sur les recherches des systemes agricoles ne prete que peu d'attention au systeme recolte et post-recolte (SRPR). II est cependant tres possible que le SRPR soit au coeur meme de tout programme de recherche des systemes agricoles tant parce que c'est en lui-meme une priorite de recherche que parce que les modifications de la technologie dans d'autres parties du systeme agricole troublent le SRPR traditionnel. Le point est illustre par une etude individuelle de Santa Cruz, en Bolivie, et les implications pour l'organisation de la recherche des systemes d'exploitation agricole sont examinees.

The mechanisms of action of morphine on the arterial system are not well understood. The aim was to report forearm vascular responses, and their mediation, to intra-arterial morphine in healthy subjects.Three separate protocols were performed: (i) dose ranging; (ii) acute tolerance; (iii) randomized crossover mechanistic study on forearm blood flow (FBF) responses to intrabrachial infusion of morphine using venous occlusion plethysmography. Morphine was infused either alone (study 1 and 2), or with an antagonist: naloxone, combined histamine-1 and histamine-2 receptor blockade or during a nitric oxide clamp.Morphine caused an increase in FBF at doses of 30 microg min(-1)[3.25 (0.26) ml min(-1) 100 ml(-1)][mean (SEM)] doubling at 100 microg min(-1) to 5.23 (0.53) ml min(-1) 100 ml(-1). Acute tolerance was not seen to 50 microg min(-1) morphine, with increased FBF [3.96 (0.35) ml min(-1) 100 ml(-1)] (P = 0.003), throughout the 30-min infusion period. Vasodilatation was abolished by pretreatment with antihistamines (P = 0.008) and the nitric oxide clamp (P0.001), but not affected by naloxone. The maximum FBF with pretreatment with combined H1/H2 blockade was 3.06 (0.48) and 2.90 (0.17) ml min(-1) 100 ml(-1) after 30 min, whereas with morphine alone it reached 4.3 (0.89) ml min(-1) 100 ml(-1).Intra-arterial infusion of morphine into the forearm circulation causes vasodilatation through local histamine-modulated nitric oxide release. Opioid receptor mechanisms need further exploration.

Evidence of poor prescribing is widespread including overuse of medicines, underuse of effective medicines, avoidable adverse drug reactions and medication errors. Junior doctors who have recently graduated are responsible for much of the prescribing that takes place in hospitals and are implicated in many of the adverse medication events. Analysis of such events suggests that lack of knowledge and training underlies many of them and it has been shown that dedicated training can increase prescribing performance. In the context of these problems, it is a matter of increasing concern that recent changes to undergraduate medical education may have reduced exposure to clinical pharmacology, a discipline dedicated to optimal practice in relation to medicines. For this reason, the European Association of Clinical Pharmacology and Therapeutics (EACPT) and British Pharmacological Society (BPS) jointly organized a meeting to explore (i) the state of undergraduate education in clinical pharmacology in Europe, (ii) the knowledge and competencies in relation to medicines that should be expected of a new graduate, (iii) assessments that might demonstrate that this minimum standard had been reached, (iv) a curriculum that might help medical students to achieve this standard and (v) how competence can be developed in the postgraduate phase. It was agreed that the lack of exposure to clinical pharmacology is a cause for concern at a time when the challenges facing junior prescribers have never been greater. The potential for undertaking further research was discussed.

Background. Wideband external pulse (WEP) monitoring, using a broad bandwidth piezoelectric sensor located over the brachial artery under the distal edge of a sphygmomanometer cuff, can be used for evaluating the contour of the arterial pressure pulse wave. The pulse contour contains valuable information relating to cardiovascular function which may be of clinical use in addition to blood pressure measurements. The aim of this study was to compare the shape of the WEP signal during inflation of the cuff to suprasystolic pressure, with intra-arterial pressure waves, after the administration of vasoactive drugs. Methods. Radial intra-arterial and suprasystolic WEP waveforms were recorded in 11 healthy men (mean 23 yr) before and at the end of infusion of glyceryl trinitrate, angiotensin II, norepinephrine, and salbutamol. Waveform similarity was assessed by comparing the timing and pressure of incident and reflected waves and by root mean square error (RMSE). Results. The WEP signal was found to closely resemble the first derivative of intra-arterial pressure. The WEP signal could be used to derive an arterial pressure wave with minimal bias in the timing of incident [28 (18) ms, mean (SD)] and reflected [21 (24) ms] waves. Augmentation index was underestimated by WEP [27 (18)%]. WEP also provided a measure of compliance which correlated with pulse wave velocity (r¼20.44). RMSE values after the administration of each of the four drugs mentioned earlier were 12.4 (3.8), 17.7 (5.0), 22.1 (11.7), and 28.9 (22.4) mm Hg, respectively. Changes in derived WEP signals were similar to those measured by arterial line with all drugs. Conclusions. The suprasystolic WEP signals can be used to derive arterial pressure waves which, although not identical, track changes in the intra-arterial pulse wave induced by vasoactive drugs. Br J Anaesth 2007; 99: 653‐61

Endothelial dysfunction contributes to excess cardiovascular risk in patients with type 2 diabetes. There is strong evidence of an association between high serum uric acid concentrations and endothelial dysfunction, and uric acid has been proposed as an independent cardiovascular risk factor in type 2 diabetes. We hypothesised that lowering of uric acid concentrations might allow restoration of endothelial function in this high-risk group.Intravenous urate oxidase (1.5 mg) was administered to ten patients with type 2 diabetes and ten healthy participants in a two-way, randomised, placebo-controlled, crossover study. Forearm blood flow responses to intra-brachial acetylcholine, sodium nitroprusside and N(G)-monomethyl-L-arginine (L-NMMA) were measured using venous occlusion plethysmography. The augmentation index (AIx) was determined by pulse wave analysis as a measure of large arterial stiffness.Acetylcholine and L-NMMA evoked lesser responses in patients with type 2 diabetes than in healthy participants. Baseline AIx was higher in patients with type 2 diabetes (mean +/- SD: 13.1 +/- 6.9%) than in healthy participants (2.0 +/- 5.1%; p = 0.006). Urate oxidase lowered serum uric acid concentrations by 64 +/- 11% (p0.001), but this had no effect on forearm blood flow responses or AIx in either group.Substantial short-term lowering of uric acid did not have a direct vascular effect, suggesting that, on its own, this might not be an effective strategy for restoring endothelial function in patients with type 2 diabetes.

This symposium was organized as a collaborative venture between the Education Subcommittee and Clinical Section Committee of the British Pharmacological Society in recognition of the slow but steady advent of nonmedical prescribing in the UK, which has created significant opportunities for improved medicines management, together with a crucial responsibility to ensure that new prescribers are appropriately prepared and competent. The intention was to provide a programme that would update Society members on recent developments in the provision of prescribing powers to nurses and other health professionals, and to advertise the Society and its resources to those with a special interest in pharmacology education for new prescribers, who are not currently members of the Society. To this end, the symposium programme focused first on context and then on content. It commenced with a brief history of the extension of prescribing rights (M.A.), followed by an analytical description of an innovatory e-learning programme designed to meet the education-for-prescribing requirements of people from a wide range of health professions (M.B. and M.A.) and an account of related issues and resources from a medical perspective (S.M.). [The DVD referred to in the symposium has since received a gold award from the International Visual Communications Association (presented 25 March 2006).] The second part explored ways in which pharmacology education can be delivered effectively for new prescribers with a limited background in chemistry (H.L.L.), with particular focus on drug interactions and cytochrome P450 (M.L.). This paper provides an overview and summary of the papers, with particular emphasis on the e-learning project.

Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.

The arterial pulse-wave transit time can be measured between the ECG R-wave and the finger pulse ( rPTT), and has been shown previously to have a linear correlation with blood pressure (BP). We hypothesized that the relationship between rPTT, preejection period (PEP; the R-wave/mechanical cardiac delay), and BP would vary with different vasoactive drugs. Twelve healthy men (mean age 22 yr) were studied. Beat-to-beat measurements were made of rPTT (using ECG and photoplethysmograph finger probe), intra-arterial radial pressure, PEP (using cardiac bioimpedance), and transit time minus PEP ( pPTT). Four drugs (glyceryl trinitrate, angiotensin II, norepinephrine, salbutamol) were administered intravenously over 15 min, with stepped dosage increase every 5 min and a 25-min saline washout between agents. All subjects in all conditions had a negative linear correlation ( R2 = 0.39) between rPTT and systolic BP (SBP), generally constant between different drugs, apart from four subjects who had a positive rPTT/SBP correlation with salbutamol. The 95% limits of agreement between measured and rPTT-predicted SBP were ±17.0 mmHg. Beat-to-beat variability of rPTT showed better coherence with SBP variability than it did with heart rate variability ( P < 0.001). PEP accounted for a substantial and variable proportion of rPTT (12–35%). Diastolic (DBP) and mean arterial BP (MAP) correlated poorly with rPTT ( R2 = 0.02 and 0.08, respectively) but better with pPTT ( rPTT corrected for PEP, R2 = 0.41 and 0.45, respectively). The 95% limits of agreement between measured and pPTT-predicted DBP were ± 17.3 mmHg. In conclusion, the negative correlation between rPTT and SBP is generally constant, even with marked hemodynamic perturbations. However, the relationship is not reliable enough for rPTT to be used as a surrogate marker of SBP, although it may be useful in assessing BP variability. DBP and MAP cannot be predicted from rPTT without correction for PEP. The significant contribution of PEP to rPTT means that rPTT should not be used as a marker of purely vascular function.

Dissension over Iraq in 2003 challenged the legitimacy and effectiveness of the UN. It also highlighted long-standing problems that previous UN institutional reform efforts had failed to resolve. Kofi Annan has been a reforming secretary-general, but even he acknowledged in September 2003 that the core UN institutions needed "radical reform." (1) The High-Level Panel on Threats, Challenges and Change was the response: (2) wide-ranging, certainly; radical, up to a point; and with at least some of its core recommendations regarding peacebuilding and protection likely implemented at the UN summit in September 2005. However, other recommendations of the High-Level Panel have proved to be problematical. These include key ideas about the composition of the Security Council and about the reform of other UN bodies. This is not surprising. The key question on UN reform has always been not "why" or "what" but "how." (3) Indeed, there have been many previous reports and recommendations, by outside bodies and by the secretary-general. (4) The high principles and values are well established. They include peace, justice, freedom, equity, sustainability, and solidarity. Earlier reports have also made many specific proposals--for example, about membership of the Security Council, the need for stronger institutions to manage the world economy, and voting rights for developing countries on the boards of the World Bank and the International Monetary Fund (IMF). Actual reform has often been slow, however, especially where changes to the core institutions are required. For example, Kofi Annan made wide-ranging recommendations when he first came to office, in a document called "Renewing the UN: A Programme for Reform." (5) Some of the ideas, described in the document as Track 1 changes, could be pursued internally and included setting up cabinet-style decisionmaking and creating a UN Development Group of Funds and Programs. Others, described as Track 2, dealt with governance arrangements, such as relations with the UN specialized agencies, and made far less progress. (6) Why should this be? Research on collective action offers not only an explanation of why countries might or might not collaborate in particular reforms, but also a way of thinking about actions and processes that might provide a greater incentive for collaboration on UN reform. In fact, an eight-step program can be proposed. We need to start with the theory. (7) At the heart of this is the idea that successful cooperation happens only when certain conditions are met. Researchers in different disciplines have discussed the conditions and have studied cases as varied as villages in India, business associations in New York, and communities of guppy fish. There is also a tradition of analysis using game theory. Sometimes, in these various pieces of research, the actors are all equal--villagers, for example, cooperating in the management of shared forest or grazing land. More often, and more usefully, because of the parallels in the real world, there are disparities in power: there may be one rich landowner, acting as a local superpower, or a shark in the tank with the guppy fish. Some of the research conclusions are unsurprising. Trust turns out to be central--the medium within which exchange takes place, the key ingredient of social capital, and the means by which transaction costs are kept as low as possible. For example, among diamond traders in New York, social networks are so dense that legal contracts are simply unnecessary. There is an important corollary, however: the group has to be small enough that knowledge can be shared. Trust is harder to achieve in large groups and is more likely to require formal institutions for dispute settlement. More generally, the likelihood of cooperation increases when the prevailing culture provides strong reinforcement: noncooperators are simply frozen out. Why, for example, do people not steal the tea bags provided in the office kitchen? …

The Africa Commission Report is an exhilarating, exhausting and intriguing read. Exhilarating because of its breadth and political impetus. Exhausting because of its ambition and the comprehensive nature of its proposals. Intriguing because of the new twists embedded in its narratives, and the intellectual challenges they pose. It is these – the intellectual challenges – which will extend the life of the Report beyond its immediate political span. Exhilarating need not detain us. There have been many reports over the years on Africa. Few have been signed by as many practising leaders, from North and South. And few have seen their recommendations translated so quickly onto the agenda of the G8, the EU Presidency and the UN. Few, it might also be said, have been as well written. Exhausting can also be covered in short order – certainly in shorter order than the 462 pages of the Report. The extended summary alone, called here ‘the argument’, extends to 58 pages. There are five substantive chapters, dealing respectively with: (i) governance and capacity building; (ii) peace and security; (iii) investing in people; (iv) growth; and (v) trade. A substantial chapter deals with resources. Other chapters set the scene, talk about the importance of culture, and discuss implementation. The substantive chapters are strongly research-based, and are packed with examples and ‘killer facts’, some of them literally so: corruption adds 25% to the cost of public procurement; an AK47 can be bought for US$6; poor infrastructure in Uganda amounts to an 80% tax on textile exports; in Zambia, by 2010, every third child will be an orphan. The recommendations run to 13 pages. They include many actions to be taken by African governments and people, especially in the area of governance and accountability, and many to be taken by developed countries or the international

Blood flow and plasma fibrinolytic factors were measured on five occasions in both forearms of eight otherwise healthy male smokers during unilateral brachial artery infusion of the endothelium-dependent vasodilator, substance P (2 to 8 pmol/min), and the endothelium-independent vasodilator, sodium nitroprusside (2 to 8 microg/min). On the first occasion, intra-arterial vitamin C was co-infused at 25 mg/min. On subsequent occasions, subjects attended after 28 and 35 days treatment with oral vitamin C (1 g daily) or placebo in a double-blind randomized crossover design still smoking but with and without acute smoke inhalation (3 cigarettes over 30 minutes). Basal plasma ascorbate concentrations increased from 37 +/- 6 micromol/L to 105 +/- 11 micromol/L following oral vitamin C supplementation (P = 0.002). Substance P caused dose-dependent increases in forearm blood flow (P0.001, ANOVA) and t-PA release (P0.05, ANOVA) that was unaffected by acute recent smoke inhalation, intra-arterial vitamin C, or oral vitamin C administration (p = ns). Likewise there were no effects on sodium nitroprusside-induced vasodilatation (p = ns). Neither acute local intra-arterial nor prolonged oral vitamin C supplementation reverses smoking-related endothelial dysfunction and impaired endogenous t-PA release. We conclude that the adverse vascular actions of smoking are not principally mediated through oxidative stress.

OBJECTIVE: To investigate the possibility that uric acid (UA) can impair endothelial function, an important surrogate for atherosclerosis.DESIGN: UA was administered locally or systemically to healthy adult men and women in a series of randomised placebo controlled studies. This temporarily raised serum UA concentrations, so that the potential effects of hyperuricaemia on mechanisms of cardiovascular disease could be studied.MAIN OUTCOME MEASURES: The effects of UA administration on basal blood flow and responses to locally administered acetylcholine, sodium nitroprusside, and L-N(G)-monomethylarginine were studied in the forearm vascular bed with venous occlusion plethysmography. The effects of hyperuricaemia on systemic vascular resistance, large artery compliance, and baroreflex sensitivity were examined by validated non-invasive techniques.RESULTS: UA administration caused a twofold increase in serum concentrations. However, there were no acute effects on haemodynamic variables, basal forearm blood flow, or nitric oxide dependent endothelial function.CONCLUSION: Unlike other risk factors associated with endothelial dysfunction, acute exposure to high concentrations of UA does not impair cardiovascular function in healthy men. These findings do not support a causal link between hyperuricaemia and atherosclerosis.

The character of the food system and the nature of food policy are both changing, as urbanisation, technical change and the industrialisation of the food system transform the way food is produced, marketed and consumed in developing countries. This overview presents an evaluation framework and explores new policy options. Some issues feature more prominently in richer, more urbanised, more industrialised developing countries, but the new food policy agenda is relevant in all countries – and it is in the poorest countries where challenges are set to emerge most rapidly. The agenda is more one of ‘food policy’ than ‘food security’: developing countries need both, but particularly a greater engagement with the new food policy.

Supplementary oxygen is commonly administered in current medical practice. However, attention has recently been drawn to the potentially disadvantageous hemodynamic consequences in certain patients. Possible mechanisms underlying the cardiovascular responses to acute hyperoxia are unclear. The effects of acute oxygen administration on heart rate, blood pressure, cardiac output, systemic vascular resistance, and baroreflex sensitivity were studied in a series of randomised, placebo-controlled studies in healthy individuals, using validated, non-invasive techniques. The effects of oxygen administration on forearm blood flow responses to locally administered acetylcholine, an endothelium-dependent vasodilator, sodium nitroprusside, an endothelium-independent vasodilator, and l-NG-monomethylarginine, a nitric oxide synthase inhibitor, were studied using venous occlusion plethysmography. Oxygen administration for 1 hour caused a reduction in heart rate (P0.01) and cardiac index (P0.05), and an increase in mean arterial pressure (P0.01), systemic vascular resistance (P0.05), large artery stiffness (P0.05), and baroreflex sensitivity (P0.05). There were no effects on vascular responses in the isolated forearm bed. These findings indicate that oxygen administration causes acute effects on cardiovascular function, which might be important in the context of acute illness.