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To compare the longer-term clinical efficacy of two occlusion-technology toothpastes - a 5% calcium sodium phosphosilicate (CSPS) toothpaste and a commercially available 8% arginine/calcium carbonate toothpaste - in relieving dentine hypersensitivity (DH). Efficacy was also compared with that of a regular fluoride toothpaste control.This was an exploratory, randomised, examiner-blind, parallel-group, 11-week, controlled study in healthy adults with self-reported and clinically diagnosed DH. After an acclimatisation period, subjects were randomised to one of three study treatments with which they brushed their teeth twice daily. Sensitivity was assessed at baseline and after 1, 2, 4, 6 and 11 weeks treatment in response to evaporative (air) and tactile stimuli (measured by the Schiff Sensitivity Scale/visual analogue scale and tactile threshold, respectively).A total of 135 subjects were randomised to treatment. The two occlusion-technology toothpastes performed similarly over the 11-week treatment period. All study treatments showed statistically significant reductions from baseline in DH at all timepoints for all measures (p0.05). Statistically significant and clinically relevant sensitivity relief was observed for both occluding formulations compared with the regular fluoride toothpaste: for evaporative (air) sensitivity within 1 week and for tactile sensitivity at Week 11. No significant differences were detected between the two occluding formulations at any timepoint, for any endpoint. Study treatments were generally well tolerated.In this exploratory study, a 5% CSPS occluding toothpaste was effective in relieving DH compared with a regular fluoride toothpaste; an 8% arginine/calcium carbonate anti-sensitivity toothpaste provided similar benefits. Improvements in DH continued throughout the 11-week study.Dentine hypersensitivity (DH) is a common and painful condition. Twice-daily use of a 5% calcium sodium phosphosilicate toothpaste reduces DH within 1-2 weeks of initiating use. Ongoing, twice daily use of the sensitivity toothpastes evaluated in this study was associated with continued, clinically significant improvements in DH.

Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

College football programs rely on recruiting to attract high-quality talent, which helps build a team's foundation and ensure success year after year. By conducting systems analysis of the current University of Virginia recruiting process and building upon Walter et al.'s work [1], the Virginia recruiting staff can gain a competitive advantage in the recruiting landscape. Analyzing Virginia's football recruiting and utilizing data analytics could provide the coaching staff with powerful tools to gain such a competitive edge. This study uses a database encompassing over 53,000 football recruits and over 200 predictive attributes to model the four aspects of collegiate football recruiting, as defined by Virginia's football coaches. Specifically, a desirable athlete is defined as one who 1) would succeed on the field at the collegiate level, 2) will meet Virginia's strict academic standards to achieve four years of playing eligibility, 3) fit Virginia football's “gritty” team culture, which is characterized by players who are resilient and able to overcome challenges, and 4) would commit to Virginia if given an offer.

This study determined the level of depression and the rate of diabetes among the adult African American female population. By identifying the population early, one can save millions of dollars, improve health outcomes, and treat depression that typically interferes with diabetes management. The study used secondary data from the 2011-2012 California Health Interview Survey. The 2011-2012 CHIS surveyed 42,935 adults and of those surveyed 1,403 respondents identified themselves as African Americans. Chi-square analysis was used to determine the strength of the association between diabetes in African American women with depression and exercise. The results of the statistical tests show that there was an association between the independent variables suggesting a statistically significant relationship in African American women. A major limitation of the study was the small number of African Americans interviewed in the survey. A larger sample size at the national level is recommended to more closely scrutinize the directional nature of the relationship between diabetes and depression in African American women.

Reactive oxygen species (ROS), when combined with various delivery mechanisms, has the potential to become a powerful novel therapeutic agent against difficult-to-treat infections, especially those involving biofilm. It is important in the context of the global antibiotic resistance crisis. ROS is rapidly active in vitro against all Gram-positive and Gram-negative bacteria tested. ROS also has antifungal and antiviral properties. ROS prevents the formation of biofilms caused by a range of bacterial species in wounds and respiratory epithelium. ROS has been successfully used in infection prevention, eradication of multiresistant organisms, prevention of surgical site infection, and intravascular line care. This antimicrobial mechanism has great potential for the control of bioburden and biofilm at many sites, thus providing an alternative to systemic antibiotics on epithelial/mucosal surfaces, for wound and cavity infection, chronic respiratory infections and possibly recurrent urinary infections as well as local delivery to deeper structures and prosthetic devices. Its simplicity and stability lend itself to use in developing economies as well.

OBJECTIVES: There is global concern that antimicrobial resistance is a major threat to healthcare. Antimicrobial use is a primary driver of resistance but little information exists about the variation in antimicrobial use in individual hospitals in England over time or comparative use between hospitals. The objective of this study was to collate, analyse and report issue data from pharmacy records of 158 National Health Service (NHS) acute hospitals. METHODS: This was a cohort study of inpatient antibacterial use in acute hospitals in England analysed over 5 years through a data warehouse from IMS Health, a leading provider of information, services and technology for the healthcare industry. Around 98% of NHS hospitals were included in a country with a population of 50 million residents. RESULTS: There was a dramatic change in the usage of different groups of antibacterials between 2009 and 2013 with a marked reduction in the use of first-generation cephalosporins by 24.7% and second-generation cephalosporins by 41%, but little change in the use of third-generation cephalosporins (+5.7%) and fluoroquinolones (+1.6%). In contrast, use of co-amoxiclav, carbapenems and piperacillin/tazobactam increased by 60.1%, 61.4% and 94.8%, respectively. There was wide variation in the total and relative amounts of antibacterials used between individual hospitals. CONCLUSIONS: Longitudinal analysis of antibacterial use demonstrated remarkable changes in NHS hospitals, probably reflecting governmental and professional guidance to mitigate the risk of Clostridium difficile infection. The wide variation in usage between individual hospitals suggests potential for quality improvement and benchmarking. Quality measures of optimal hospital antimicrobial prescribing need urgent development and validation to support antimicrobial stewardship initiatives.

Antimicrobial resistance (AMR) has become a global problem for health care services, with fewer antimicrobials entering the market and some pathogenic organisms becoming resistant to commonly used antimicrobials. Antimicrobial stewardship (AS), including evidence-based standard setting, education and communication, and audits of practice, has become a key method of preventing the rise in the rise in AMR. Data on antibiotic consumption are often obtained through prospective and retrospective point prevalence audits of antibiotic usage, but such studies are very resource intensive and only provide a snapshot of consumption. The objective of the study reported here was to examine longitudinal total antibacterial usage at a national level and cross-sectional usage at an individual hospital trust level using a commercial database that captures antimicrobial prescribing from at least 99% of English hospital Trusts.

Objective: A pilot evaluation was performed to assess the effects of Surgihoney, an engineered honey with highly active antimicrobial activity, on bacterial colonisation in long lines in oncology patients. Method: This prospective service evaluation was conducted at Hampshire Hospitals NHS Foundation Trust (HHFT) in England, UK, between 2012 and 2013. The study population consisted of oncology patients with central intravenous lines who were receiving outpatient chemotherapy. All patients were offered line dressing with or without Surgihoney, applied to the line exit site. Results: The primary outcome measure of the study was the presence or absence of bacterial colonisation of the line site. There were 30 patients in each arm – with or without Surgihoney. In the Surgihoney arm, 2 patients with existing line site colonisation were cleared of bacterial colonisation and none acquired colonisation during the study period. In the non-treatment arm, 6 patients were colonised at the line site prior to screening or during the evaluation. Bacterial colonisation was maintained throughout the period. Conclusion: Surgihoney is an effective antimicrobial line-site dressing, significantly reducing line site colonisation and eradicating existing colonisation. It was well tolerated by the patients. Declaration of interest: Surgihoney supplies were donated by Healing Honey International (HHI) who also provided some funding to Hampshire Hospitals Foundation Trust for microbiological investigation. MD and JC have provided clinical advice in an advisory capacity to HHI.

PURPOSE OF REVIEW: This review looks at the recent evidence on the safety, toxicity, microbiology and the prevention and management of acute and chronic wound infections with regard to antiseptics and antiseptic wound dressings. It is timely and relevant because of the global concerns of antimicrobial resistance and the need to address the inappropriate use of antimicrobials in the healthcare setting. RECENT FINDINGS: There have been a number of recent Cochrane reviews that have concluded that there is little evidence to delineate clinical outcomes between antiseptics and antiseptic dressings. Published in-vitro evidence offers some new techniques and evaluates some new dressings and antiseptics. There are no economic evaluations of antiseptics and antiseptic dressings. SUMMARY: Better clinical trials on the effectiveness and cost-effectiveness of wound dressings are needed to ensure evidence-based guidance is developed for optimizing the treatment of patients. It is surprising that with the paucity of evidence of clinical effectiveness, healthcare organizations continue to spend considerable resources on poorly evaluated topical wound products.

Caesarean section (CS) wound infection rates are unacceptably high; around 10% according to figures from the Health Protection Agency (2012) . This service evaluation assessed the effects of Surgihoney on surgical site infection rates in women undergoing caesarean section. All women presenting for CS were offered Surgihoney as a single application wound dressing at the end of the procedure. All women were followed up and examined for surgical site infection for 30 days after CS. A single application of Surgihoney dressing reduced surgical site infection (SSI) by 60.33% from a rate of 5.42% (n=590) to 2.15% (n=186) (p-value=0.042). The potential saving to the NHS of using Surgihoney as a single application achieving this level of wound infection reduction is considerable. Surgihoney offers a simple, cost-effective intervention to reduce SSI in women undergoing CS. It is applicable to practice in all health economies and could potentially save considerable surgical infective morbidity in patients undergoing surgical delivery.

Asylum seekers receiving housing and subsistence support from the Home Office are routinely dispersed to areas outside London. Pregnant women seeking asylum have often been dispersed very late in their pregnancies, and in some cases very soon after delivery ( Reynolds and White, 2010 ; Beecher Bryant, 2011 ). A study carried out by Maternity Action and the Refugee Council ( Feldman, 2013 ) investigated the experiences of women who had been dispersed during pregnancy and of midwives involved in the care of such women. It found that dispersal policies and procedures failed to take account of the vulnerabilities and special needs of this group of women, despite recognition by the National Institute for Health and Care Excellence (NICE) that they required additional support ( NICE, 2010a ). Women found the experience of dispersal and its impact distressing. Dispersal interrupted established maternity care and left women without social and family support, and many gave birth alone. Midwives' efforts to create rapport and trust and to establish multiagency and specialist support were undermined. The study advocated radical changes in Home Office dispersal policy for pregnant women. This article is based on the findings and report of the larger study ( Feldman, 20 13).

Background Underlying systems factors have been seen to be crucial contributors to the occurrence of medication errors. By understanding the causes of these errors, the most appropriate interventions can be designed and implemented to minimise their occurrence. Objective This study aimed to systematically review and appraise empirical evidence relating to the causes of medication administration errors (MAEs) in hospital settings. Data Sources Nine electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, ASSIA, PsycINFO, British Nursing Index, CINAHL, Health Management Information Consortium and Social Science Citations Index) were searched between 1985 and May 2013. Study Selection Inclusion and exclusion criteria were applied to identify eligible publications through title analysis followed by abstract and then full text examination. English language publications reporting empirical data on causes of MAEs were included. Reference lists of included articles and relevant review papers were hand searched for additional studies. Studies were excluded if they did not report data on specific MAEs, used accounts from individuals not directly involved in the MAE concerned or were presented as conference abstracts with insufficient detail. Data Appraisal and Synthesis Methods A total of 54 unique studies were included. Causes of MAEs were categorised according to Reason’s model of accident causation. Studies were assessed to determine relevance to the research question and how likely the results were to reflect the potential underlying causes of MAEs based on the method(s) used. Results Slips and lapses were the most commonly reported unsafe acts, followed by knowledge-based mistakes and deliberate violations. Error-provoking conditions influencing administration errors included inadequate written communication (prescriptions, documentation, transcription), problems with medicines supply and storage (pharmacy dispensing errors and ward stock management), high perceived workload, problems with ward-based equipment (access, functionality), patient factors (availability, acuity), staff health status (fatigue, stress) and interruptions/distractions during drug administration. Few studies sought to determine the causes of intravenous MAEs. A number of latent pathway conditions were less well explored, including local working culture and high-level managerial decisions. Causes were often described superficially; this may be related to the use of quantitative surveys and observation methods in many studies, limited use of established error causation frameworks to analyse data and a predominant focus on issues other than the causes of MAEs among studies. Limitations As only English language publications were included, some relevant studies may have been missed. Conclusions Limited evidence from studies included in this systematic review suggests that MAEs are influenced by multiple systems factors, but if and how these arise and interconnect to lead to errors remains to be fully determined. Further research with a theoretical focus is needed to investigate the MAE causation pathway, with an emphasis on ensuring interventions designed to minimise MAEs target recognised underlying causes of errors to maximise their impact.

OBJECTIVE:To systematically review empirical evidence on the prevalence and nature of medication administration errors (MAEs) in health care settings.DATA SOURCES:Ten electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, Scopus, Applied Social Sciences Index and Abstracts, PsycINFO, Cochrane Reviews and Trials, British Nursing Index, Cumulative Index to Nursing and Allied Health Literature, and Health Management Information Consortium) were searched (1985-May 2012).STUDY SELECTION AND DATA EXTRACTION:English-language publications reporting MAE data using the direct observation method were included, providing an error rate could be determined. Reference lists of all included articles were screened for additional studies.DATA SYNTHESIS:In all, 91 unique studies were included. The median error rate (interquartile range) was 19.6% (8.6–28.3%) of total opportunities for error including wrong-time errors and 8.0% (5.1–10.9%) without timing errors, when each dose could be considered only correct or incorrect. The median rate of error when more than 1 error could be counted per dose was 25.6% (20.8–41.7%) and 20.7% (9.7–30.3%), excluding wrong-time errors. A higher median MAE rate was observed for the intravenous route (53.3% excluding timing errors (IQR 26.6–57.9%)) compared to when all administration routes were studied (20.1%; 9.0–24.6%), where each dose could accumulate more than one error. Studies consistently reported wrong time, omission, and wrong dosage among the 3 most common MAE subtypes. Common medication groups associated with MAEs were those affecting nutrition and blood, gastrointestinal system, cardiovascular system, central nervous system, and antiinfectives. Medication administration error rates varied greatly as a product of differing medication error definitions, data collection methods, and settings of included studies. Although MAEs remained a common occurrence in health care settings throughout the time covered by this review, potential targets for intervention to minimize MAEs were identified.CONCLUSIONS:Future research should attend to the wide methodological inconsistencies between studies to gain a greater measure of comparability to help guide any forthcoming interventions.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Reactive oxygen species (ROS) is a novel therapeutic strategy for topical or local application to wounds, mucosa or internal structures where there may be heavy bacterial bioburden with biofilm and chronic inflammation. Bacterial biofilms are a significant problem in clinical settings owing to their increased tolerance towards conventionally prescribed antibiotics and their propensity for selection of further antibacterial resistance. There is therefore a pressing need for the development of alternative therapeutic strategies that can improve antibiotic efficacy towards biofilms. ROS has been successful in treating chronic wounds and in clearing multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and carbapenemase-producing isolates from wounds and vascular line sites. There is significant antifungal activity of ROS against planktonic and biofilm forms. Nebulised ROS has been evaluated in limited subjects to assess reductions in bioburden in chronically colonised respiratory tracts. The antibiofilm activity of ROS could have great implications for the treatment of a variety of persistent respiratory conditions. Use of ROS on internal prosthetic devices shows promise. Avariety of novel delivery mechanisms are being developed to apply ROS activity to different anatomical sites.

Objectives The Antimicrobial Self-Assessment Toolkit for National Health Service (NHS) Trusts (ASAT) was developed to evaluate hospital-based antimicrobial stewardship programmes. Iterative validity investigations of the ASAT were used to produce a 91-item ASAT v17 utilizing qualitative methodology. Rasch analysis was used to generate question (item) behaviour estimates and to investigate the validity of ASAT v17. Methods In 2012, the partial credit model (PCM) was used to analyse ASAT responses from 33 NHS Trusts within England. WINSTEPS® outputs such as fit statistics and respondent/item maps were examined to determine unidimensionality, item discrimination and item hierarchy. Ordinary least squares regression modelling was used to determine the predictive validity using NHS Trust ability estimates generated from the PCM and corresponding Clostridium difficile rates. Results Each domain contained items that were misfitting the PCM (with INFIT MNSQ 1.3), except Domain 3. Subsequent iterative item removal had a negligible effect on the fit indices within most ASAT domains. Scale analysis demonstrated that most items were productive for measurement (n = 81). Respondent/item maps showed ceiling effects (n = 3) and floor effects (n = 1) within ASAT domains. Ordinary least squares regression modelling identified that there was limited predictive validity due to the small positive correlation between the predictor and outcome variables for participating hospitals (ρ = 0.146; P = 0.418). Conclusions Rasch analysis was an effective measurement technique for evaluating the validity of ASAT v17 by providing evidence that each sub-scale and the overall scale demonstrated unidimensionality (construct validity). Improved item targeting may be required to improve item discrimination within the toolkit.

Background The Antimicrobial Self-Assessment Toolkit for NHS Trusts (ASAT) was developed in England by a National Pharmacist Reference Group of an Advisory Non-Departmental Public Body on Antimicrobial Resistance and Healthcare Associated Infections (ARHAI), in conjunction with the Department of Health. It is intended to identify and evaluate interventions for the promotion and implementation hospital-based antimicrobial stewardship programmes (ASPs). ASAT v16 was produced by iterative validity testing with end-users utilising a sequential exploratory strategy. It was highlighted that there was a need for the inclusion of the domain which targeted the role of clinical microbiologists due to their substantial roles in hospital-based ASP development and implementation. Methods This study aimed to investigate the content validity of ASAT v16 and a proposed draft domain for clinical microbiologists and hence produce ASAT v17. From June to September 2011, semi-structured interviews were conducted with ten consultant clinical microbiologists from secondary and tertiary care National Health Service (NHS) Trusts within England. Interviews were conducted until no novel themes were identified i.e., data saturation was achieved. Each interview was digitally recorded and transcribed verbatim and then analysed using a thematic framework that facilitated the identification of emergent themes and sub-themes. Results Nine emergent themes were identified which included common enablers and challenges associated with the implementation of effective and sustainable hospital-based ASPs. Key themes included formal governmental mandates, IT infrastructure and also prescribers’ knowledge base of antimicrobial chemotherapy and infectious diseases. Most respondents agreed with the content of ASATv16 and the proposed draft section however they suggested that minor modifications were required to improve question sensitivity and hence reduce measurement error. Conclusions Although, the ASAT been through multiple iterations and content validity testing, further modifications were required to produce the next iteration, ASAT v17. Question merging and other minor modifications were conducted as indicated by study findings. This study reinforces the need for stakeholder engagement during the development and implementation of tools that evaluate hospital-based implementation strategies.

To describe the methodology in developing an antimicrobial self-assessment toolkit (ASAT).The ASAT was developed through a National Pharmacy Reference Group using an evidence-based approach of published information and national reports to identify criteria for inclusion. These were subdivided into domains that addressed: 1) Antimicrobial management within the Trust-structures and lines of responsibility and accountability-high-level notification to the Board. 2) Operational delivery of an antimicrobial strategy-operational standards of good antimicrobial stewardship. 3) Risk assessment for antimicrobial chemotherapy. 4) Clinical governance assurance. 5) Education and training-training needs and delivery of education and training for all who issue, prescribe and administer antimicrobials. 6) Antimicrobial pharmacist-systems in place for ensuring their optimum use. 7) Patients, Carers and the Public-information needs of patients, carers and the public.A web-based toolkit was developed using information from national reports and guidance on antimicrobial stewardship. The toolkit offers a checklist for hospitals to self-assess their organizations' levels of antimicrobial stewardship.The ASAT offers a web-enabled, version-controlled instrument for the assessment of antimicrobial stewardship in acute hospitals. It may offer a sensitive instrument to assess longitudinal progress on antimicrobial stewardship in an individual institution or act as a benchmark with similar organizations. Further work is ongoing to evaluate and further refine the ASAT.

This report describes the work of the Human Prescribing Subgroup of the Department of Health (DH) Specialist Advisory Committee on Antimicrobial Resistance over a period of 3 years from 2003. It describes the coordination and outputs from the DH Pharmacy Initiative for promoting prudent use of antibiotics in hospitals. The production and dissemination of a template have supported this and have provided a format for acute hospitals to develop antimicrobial guidelines. Engagement with key stakeholders has enabled antimicrobial use and resistance to be highlighted as an important policy issue. Work with the Healthcare Commission has informed the development of high-level indicators that have been incorporated into national audits of acute hospitals and recommendations in a national report 'The Best Medicine'. The development of a quantitative database of antimicrobial usage has been an important feature of this work. Three annual national multidisciplinary conferences have been organized where work has been presented.

Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound‐healing response. They act as secondary messengers to many immunocytes and non‐lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound‐healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound‐healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

Antimicrobial resistance is a global problem and is being addressed through national strategies to improve diagnostics, develop new antimicrobials and promote antimicrobial stewardship. A narrative review of the literature was undertaken to ascertain the value of C reactive protein (CRP) and procalcitonin, measurements to guide antibacterial prescribing in adult patients presenting to GP practices with symptoms of respiratory tract infection (RTI). Studies that were included were randomised controlled trials, controlled before and after studies, cohort studies and economic evaluations. Many studies demonstrated that the use of CRP tests in patients presenting with RTI symptoms reduces antibiotic prescribing by 23.3% to 36.16%. Procalcitonin is not currently available as a point-of-care testing (POCT), but has shown value for patients with RTI admitted to hospital. GPs and patients report a good acceptability for a CRP POCT and economic evaluations show cost-effectiveness of CRP POCT over existing RTI management in primary care. POCTs increase diagnostic precision for GPs in the better management of patients with RTI. CRP POCT can better target antibacterial prescribing by GPs and contribute to national antimicrobial resistance strategies. Health services need to develop ways to ensure funding is transferred in order for POCT to be implemented.

To examine the types of prescribing, administration and dispensing incidents reported to an on-line incident-reporting scheme and determine the types of healthcare professionals responsible for reporting such incidents. Retrospective analysis of medication-related incidents reported to an on-line incident-reporting scheme in a large (1000-bed) teaching hospital in the UK. Frequency and type of incidents, the discipline of the health care professional who reported the incident and the stage in the medication use process (prescribing, dispensing, or administration) at which the incident occurred. Over a 26-month study period, there were 495 medication-related incidents reported, of which 38.6% (191) were classified to be a “near miss”. Medication-related incidents were reported most often at the stages of administration (230, 46.5%) and prescribing (192, 38.8%), whilst incidents involving dispensing or supply of medication were reported less often (73, 14.7%). Of all the incidents, pharmacists reported 51.9% (257), nursing staff reported 37.6% (186), and doctors reported 9.1% (45). Cardiovascular (149, 30.1%), central nervous system (106, 21.4%), and antibiotic/anti-infective medication (71, 14.3%) were the most common therapeutic categories associated with reports of medication-related incidents. An on-line reporting scheme can be used to monitor medication-related incidents at key stages in the medication-use process in secondary care. The types of incidents reported by health care professionals differ markedly, with fewer medication-related incidents being reported by doctors. Future research should explore the prevailing safety culture amongst the different health care disciplines, and examine the impact that information technology has on the willingness of health care professionals to report adverse incidents.

PURPOSE: The methods currently used by English National Health Service (NHS) hospitals to manage the use of medicines were studied. METHODS: A questionnaire was mailed to directors of pharmacy at all English NHS hospitals in May 2001. RESULTS: The response rate was 57% (157/ 275). Sixty-six percent of the responding hospitals provided general acute care services, and 34% provided mental health services. About 1 responder in 5 (19%) was a specialty hospital functioning either as a freestanding institution or alongside other hospitals. The average total expenditure by the hospital trusts was pound 94 million (dollar 175 million), of which drugs accounted for pound 3.5 million (dollar 6.5 million). Many hospitals either had formularies or were constructing them (86%), and most hospitals used a process to manage the introduction of new medicines. About three fourths of the hospitals had < or = 20 pharmacist full-time equivalents. The implementation of national guidelines was variable, although some of this variation may have been due to differences in service provision. Few hospitals were actively monitoring compliance with guidelines (31%), but audits of current care were common (72%). CONCLUSION: A survey of English NHS hospitals provided information on pharmacy staffing, drug expenditures, and measures taken to ensure rational medication use.

From 2000 to 2004, primary care organisations (PCOs) in England were legally required to operate a prescribing incentive scheme for their general practices. A statutory framework specified the types of target, maximum rewards and use of ‘good cause for failure’ provisions that schemes should include. Our objective was to explore whether schemes might be a useful approach to encourage ‘good quality’ prescribing. We requested copies of the original schemes from all PCOs in England in 2001 and 2002. Data were extracted on the rewards offered, types of budgetary targets set and additional conditions specified. Many schemes had not been finalised, some PCOs had no scheme, and one scheme operated without rewards. Although schemes covered similar therapeutic areas, they varied considerably in their length, complexity, reward levels and reward structure. Over half the schemes contained no ‘good cause for failure’ provision. PCOs are offering diverse incentives to general practices and some have interpreted the statutory framework imaginatively. Better use of the ‘good cause for failure’ provision may help to overcome inflationary pressures on prescribing, but further research is needed to clarify the role of financial incentives in influencing prescribing.

Objective: The rapid rise of prescribing expenditure is a concern in many industrialised countries and methods to manage medicines are widely employed. The purpose of this study was to identify the approaches to improve primary care prescribing by primary care organisations (PCOs) in the National Health Service (NHS) in England. Methods: A questionnaire (Management of Medicines, MANMED) was mailed to prescribing advisers and prescribing leads in 332 PCOs. Results: A response rate of 66% (220/332) was achieved. Most PCOs report the improvement of the quality of prescribing as their top priority, followed by budget adherence at both practice and PCO levels. Prescribing advisers typically offer several forms of support: practice visits, prescribing reviews, indicators of prescribing, prescribing newsletters, hands-on support, seminars and local formularies. PCOs are pursuing a wide range of prescribing initiatives, covering, on average, seven different therapeutic areas. National targets are the main driver for prescribing initiatives but other key influences include inappropriate prescribing and clinical governance. Although cost considerations are important, improving the quality of prescribing is perceived as the overriding principle on which PCO prescribing strategy is based. Multifaceted prescribing support is widespread and national targets are the largest single factor influencing choice of therapeutic area for prescribing initiatives. Conclusions: Diversity in approaches presents the opportunity to improve the evidence base for medicines management. Not only could such research inform PCOs in their central aim of improving the quality of prescribing within the NHS, but it may also offer insights of relevance to other countries if the influence of process and context upon the effectiveness of medicines management is systematically explored.

To estimate the costs and benefits for a UK hospital pharmacy of stocking a single low molecular weight heparin (LMWH), enoxaparin, compared to stocking unfractionated heparin (UFH) and stocking both UFH and multiple different LMWHs.A decision-tree model was developed which considered the use of heparins for five indications: prophylaxis against venous thromboembolism (VTE) in major orthopaedic surgery; VTE prophylaxis in major general surgery; VTE prophylaxis in acute medical inpatients; treatment of diagnosed VTE; and anticoagulation for patients with unstable angina and non-ST-elevation myocardial infarction (UA/NSTEMI). Previously published cost-effectiveness analyses for each indication were combined into a single model and updated to 2002 prices. The number of patients given heparin in each indication was estimated from the pharmacy records of a large UK teaching hospital. The model estimated the use of drugs, staff time, clinical events and resource use resulting from anti-coagulation. Costs were estimated from the perspective of the hospital and the UK National Health Service.Total annual cost was estimated to be pounds sterling 3.2 m (single LMWH), pounds sterling 4.4 m (UFH only) and pounds sterling 3.7 m (multiple heparins). The largest expected cost savings from using a single LMWH compared to UFH only resulted from reduced hospital stay for DVT treatment, reduced revascularisation in UA/NSTEMI and fewer VTE events in orthopaedic surgery. Expected cost savings from using a single LMWH compared to multiple heparins were more modestSub-optimal choice of anticoagulants may result in substantial excess costs elsewhere in the hospital.

The systematically 'handed', or directionally asymmetrical way in which the major viscera are packed within the vertebrate body is known as situs. Other less obvious vertebrate lateralisations concern cognitive neural function, and include the human phenomena of hand-use preference and language-associated cognitive partitioning. An overview, rather than an exhaustive scholarly review, is given of recent advances in molecular understanding of the mechanism that ensures normal development of 'correct' situs. While the asymmetry itself and its left/right direction are clearly vertebrate-conserved characters, data available from various embryo types are compared in order to assess the likelihood that the developmental mechanism is evolutionarily conserved in its entirety. A conserved post-gastrular 'phylotypic' stage, with left- and right-specific cascades of key, orthologous gene expressions, clearly exists. It now seems probable that earlier steps, in which symmetry-breaking information is reliably transduced to trigger these cascades on the correct sides, are also conserved at depth although it remains unclear exactly how these steps operate. Earlier data indicated that the initiation of symmetry-breaking had been transformed, among the different vertebrate classes, as drastically as has the anatomy of pre-gastrular development itself, but it now seems more likely that this apparent diversity is deceptive. Ideas concerning the functional advantages to the vertebrate lifestyle of a systematically asymmetrical visceral packing arrangement, while untestable, are accepted because they form a plausible adaptationist 'just-so' story. Nevertheless, two contrasting beliefs are possible about the evolutionary origins of situs. Major recent advances in analysis of its developmental mechanism are largely due not to zoologists, comparative anatomists or evolutionary systematists, but to molecular geneticists, and these workers have generally assumed that the asymmetry is an evolutionary novelty imposed on a true bilateral symmetry, at or close to the origin of the vertebrate clade. A major purpose of this review is to advocate an alternative view, on the grounds of comparative anatomy and molecular systematics together with the comparative study of expressions of orthologous genes in different forms. This view is that situs represents a co-optation of a pre-existing, evolutionarily ancient non-bilaterality of the adult form in a vertebrate ancestor. Viewed this way, vertebrate or chordate origins are best understood as the novel imposition of an adaptively bilateral locomotory-skeletal-neural system, around a retained non-symmetrical 'visceral' animal. One component of neuro-anatomical asymmetry, the habenular/parapineal one that originates in the diencephalon, has recently been found (in teleosts) to be initiated from the same 'phylotypic' gene cascade that controls situs development. But the function of this particular diencephalic asymmetry is currently unclear. Other left-right partitionings of brain function, including the much more recently evolved, cerebral cortically located one associated with human language and hand-use, may be controlled entirely separately from situs even though their directionality has a particular relation to it in a majority of individuals. Finally, possible relationships are discussed between the vertebrate directional asymmetries and those that occur sporadically among protostome bilaterian forms. These may have very different evolutionary and molecular bases, such that there may have been constraints, in protostome evolution, upon any exploitation of left and right for complex organismic, and particularly cognitive neural function.

In the last few years, an understanding has emerged of the developmental mechanism for the consistent internal left-right structure, termed situs, that characterises vertebrate anatomy. This involves largely vertebrate-conserved (i.e. 'phylotypic') gene expression cascades that encode 'leftness' and 'rightness' in appropriate tissues either side of the embryo's midline soon after gastrulation. Recent evidence indicates that the initial, directional symmetry breaking that initiates these cascades utilises mechanisms that are conserved or at least closely related in different vertebrate types. I describe a scenario whereby the capacity for directional modification of an otherwise bilateral body plan can be viewed as an adaptive innovation rather closely connected with vertebrate origins, enabling optimal 'design' for very active lifestyles. But an alternative scenario, while retaining the view that situs and indeed other vertebrate functional lateralisations are deeply adaptive, proposes that they originated in the co-optation of left-right developmental information inherited from a very early stage in metazoan diversification. It is proposed that a remote chordate ancestor lost its original or 'ur-bilaterian' symmetry to pass through an altogether non-symmetrical stage, and that the vertebrate dorsoventral midline plane is not descended from that original one. I review the considerable evidence in favour of this scenario, and discuss its wider implications for directional asymmetries across the Metazoa.

BACKGROUND: The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality. OBJECTIVES: To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues. METHODS: The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months. RESULTS: In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01). CONCLUSIONS: The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths. ispartof: Journal of hypertension vol:21 issue:12 pages:2409-2417 ispartof: location:Prague, Czech Repubic status: published

Central arterial pressure, measured close to the heart, may be of more patho-physiological importance than conventional non-invasive cuff blood pressure. The technique of applanation tonometry using SphygmoCor® has been proposed as a non-invasive method of estimating central pressure. This relies on mathematically derived generalized transfer functions, which have been previously validated using invasive peripheral pressure measurements. We compared simultaneous estimates of central aortic pressure using this technique with those measured directly during the routine diagnostic cardiac catheterization of 30 subjects (age range 27–84 years), half of whom were aged 65 years or more. This was done by applanating the left radial artery and recording the non-invasive brachial cuff blood pressure to generate a central aortic pressure estimate, using the SphygmoCor® radial transfer function. The comparative results were analysed using Bland—Altman plots of mean difference. SphygmoCor®, on average, underestimated systolic central arterial pressure by 13.3 mmHg and overestimated diastolic pressure by 11.5 mmHg. The results were similar in patients aged under and above 65 years. Furthermore, non-invasively measured brachial pressures were seen to give an overall closer estimate of the central arterial pressure than the SphygmoCor® system. The transfer function has been validated from invasively measured arterial pressures and the current use by the system of non-invasive measures may explain the discrepancies. However, age, drugs and arterial disease would also be expected to play a role.

The goal of this project, an animation-based tutor for algebra word problems, is to build instructional software to improve estimation, reasoning, and problem-solving skills. In this study, we focused on the 2nd (task completion) module, which uses tank-filling problems in which the unknown variable is the time it will take to fill a tank. Students build on the answers to a simple (no leak) problem to estimate, and then calculate, answers to problems in which there is a leak in the bottom of the tank, a leak in the side of the tank, and a delay in starting one of the pipes. We evaluated the software in an intermediate algebra class consisting of a diverse group of students at a community college. We use the findings to discuss what works (estimation and the solution of the simpler problems) and to make recommendations on how to improve use of the decomposition method for solving the more complex problems.

BACKGROUND: Terminal digit and single-number preference may produce inaccuracy and biased results when measuring blood pressure. We describe these preferences in the Syst-Eur randomized placebo-controlled trial of the treatment of isolated systolic hypertension and describe how we sought to eliminate these problems. METHODS: The Data Monitoring Committee of the trial conducted yearly quality control meetings in Belgium and visited the participating centres to check their adherence to the protocol. These meetings involved identifying terminal digit preference, improving blood pressure control and boosting recruitment. RESULTS: The prevalence of use of terminal digit zero when measuring sitting systolic blood pressure (first readings) reduced from an average of 42.4% in the year prior to the date when a centre first randomized a patient to 31.5, 25, 22.3, 26.3, 23.2 and 22% in the subsequent 6 years. This trend was independent of the calendar year during which a centre entered the trial and supports the hypothesis that data-quality monitoring, including the feedback of digit preference to centres, led to a reduction in terminal digit zero preference. In addition, a higher than expected prevalence of the systolic blood pressure value of 148 mmHg was found in the active treatment groups in the double-blind phase. Selection for 148 mmHg persisted over time and constituted a single-number preference bias. This arose from the instruction to investigators to reduce systolic blood pressure to below 150 mmHg. CONCLUSION: Monitoring and feedback of data quality should be undertaken to minimize digit and number preference. Automatic devices should ideally be employed to help to avoid these problems as long as the devices are fully validated and regularly serviced, and providing that readings are not rejected and repeated. ispartof: Blood pressure monitoring vol:7 issue:3 pages:169-77 ispartof: location:England status: published

Background: Hospitalised patients with respiratory tract infections (RTI) frequently receive intravenous %lpar;IV) antibiotics followed by a short course of oral treatment.Objectives: To observe antibiotic use in hospitals in Germany, Spain, France, Italy and the UK and the reasons for choosing the IV route and switching to oral treatment. Methods: Research pharmacists sought the opinions of physicians and senior nurses in the completion of a semi-structured questionnaire on the treatment of RTI with IV antibiotics. Questions focussed on antimicrobials of choice, reasons for choosing IV, reasons for changing to oral administration, and duration of treatment.Results: This study recruited 796 patients with RTI, usually pneumonia. Prescribing patterns varied widely between the five hospitals. Accepted clinical criteria were only commonly cited in Germany, Spain and the UK as reasons for choosing the IV route at the beginning of the study. These were more commonly cited at the time of switch, although other criteria such as improved condition, were other significant reasons. The mean duration of IV treatment ranged from 4 days in the UK to 10 days in Italy, where most patients received the full course of treatment by the IV route. Unlike the other hospitals studied, the few patients in Italy who were switched to another form of treatment were as likely to receive intramuscular as oral administration (13% and 11%, respectively). Conclusions: The practice of and reasons for prescribing IV antibiotics varied in the hospitals studied. Objective clinical criteria were inconsistently cited as reasons for administering IV antibiotics and in general these reasons were unrelated to those given for the switch from IV to oral administration. In order for guidelines for switching from IV to oral antimicrobials to be routinely employed, explicit physiological criteria need to be recorded in a routine fashion. Closer co‐operation between pharmacists and physicians may help in developing and implementing guidelines at a local level.

WHAT IS KNOWN AND OBJECTIVE: The Antimicrobial Self-Assessment Toolkit for NHS Trusts (ASAT) was developed to evaluate the organizational strategies used to implement hospital-based antimicrobial stewardship programmes. An iterative approach was used to develop ASAT v15a, which has been previously investigated for face validity; however, further investigation into other types of validity was required. Therefore, the aim of this study was to investigate the content validity of ASAT v15a and hence modify and improve the content validity of the toolkit. METHODS: A purposive sample of eight antimicrobial pharmacists was interviewed using cognitive interviewing techniques from within the former North-west Strategic Health Authority in England. Respondents were asked to 'think aloud' and to verbally express their thought processes as they generated responses to each question with the ASAT. RESULTS: There were no cognitive difficulties reported by respondents in response to 26/83 (31�3%) questions within the ASAT. However, cognitive difficulties were reported by respondents at each stage of the cognitive processing pathway in response to 57/83 (68�7%) questions. These difficulties were comprehension/interpretation in 27/83 (32�5%) questions, information retrieval in 10/83 (12%) questions, judgment/decision in 6/83 (7�2%) questions and response generation/formatting in 13/83 (15�7%) questions. Other findings included disagreement with the weightings applied to 13/83 (15�7%) questions. Respondents recommended that these questions should be modified to reflect their impact on hospital-based antimicrobial stewardship programmes (ASPs). Based on these findings, modifications were made to ASAT v15a to produce the next iteration (ASAT v16). Furthermore, respondents indicated that the role of clinical microbiologists was underrepresented in the current version of the toolkit; therefore, seven proposed questions were drafted, based on a literature review. WHAT IS NEW AND CONCLUSION: Cognitive interviews were effectively able to detect problems encountered by respondents along the cognitive processing pathway by identifying words and/or phrases that required further modifications. Also, this method highlighted that there was a disparity between the respondents' interpretation and the ASAT developers' intent within some questions. Although respondents indicated that the toolkit evaluated the most pertinent components of ASPs, further modifications and testing would be required to improve its validity. These results highlight the importance of the inclusion of end-users in the development of reporting and/or evaluation tools or questionnaires.

This study aimed to determine the association between the reduction in the number of Clostridium difficile infection (CDI) cases reported by the English National Health Service (NHS) hospitals and concurrent antimicrobial use.A retrospective ecological study for January 2005 to December 2008 was conducted using data from 26 of the 29 NHS trusts (i.e. a trust manages one or more hospitals) located in the North West Strategic Health Authority of England. Antimicrobial use data, for patients of all ages, were provided by IMS Health, and CDI case data for patients aged ≥65 years were provided by the Health Protection Agency. Antimicrobial use was converted into defined daily doses (DDDs). The overall association between antimicrobial use and CDI for the trusts was investigated using multilevel models.Our study shows a positive significant association between the CDI cases and the use of the following antimicrobials: ‘third-generation cephalosporins’ [11.62 CDI cases per 1000 DDDs; 95% confidence interval (CI), 5.92–17.31]; ‘fluoroquinolones’ (4.79 CDI cases per 1000 DDDs; 95% CI, 2.83–6.74); and ‘second-generation cephalosporins’ (4.25 CDI cases per 1000 DDDs; 95% CI, 1.66–6.83). The strength of this association was not significantly different (95% CI) among the antimicrobial groups.This study shows that the reduction in the number of CDI cases reported by the English NHS hospitals is associated with concurrent reductions in antimicrobial use. This means that the number of CDI cases over time decreased in a similar fashion to the usage of various antimicrobials.

There is a need to identify effective interventions to minimize the threat posed by medication administration errors (MAEs). Our objective was to review and critically appraise interventions designed to reduce MAEs in the hospital setting. Ten electronic databases were searched between 1985 and November 2013. Randomized controlled trials (RCTs) and controlled trials (CTs) reporting rates of MAEs or related adverse drug events between an intervention group and a comparator group were included. Data from each study were independently extracted and assessed for potential risk of bias by two authors. Risk ratios (RRs, with 95 % confidence intervals [CIs]) were used to examine the effect of an intervention. Six RCTs and seven CTs were included. Types of interventions clustered around four main themes: medication use technology (n = 4); nurse education and training (n = 3); changing practice in anesthesia (n = 2); and ward system changes (n = 4). Reductions in MAE rates were reported by five studies; these included automated drug dispensing (RR 0.72, 95 % CI 0.53–1.00), computerized physician order entry (RR 0.51, 95 % 0.40–0.66), barcode-assisted medication administration with electronic administration records (RR 0.71, 95 % CI 0.53–0.95), nursing education/training using simulation (RR 0.17, 95 % CI 0.08–0.38), and clinical pharmacist-led training (RR 0.76, 95 % CI 0.67–0.87). Increased or equivocal outcome rates were found for the remaining studies. Weaknesses in the internal or external validity were apparent for most included studies. Theses and conference proceedings were excluded and data produced outside commercial publishing were not searched. There is emerging evidence of the impact of specific interventions to reduce MAEs in hospitals, which warrant further investigation using rigorous and standardized study designs. Theory-driven efforts to understand the underlying causes of MAEs may lead to more effective interventions in the future.

Inappropriate antibiotic use and antibiotic resistance are now major global issues. Antimicrobial stewardship programmes are increasingly being used to optimize antibiotic prescribing in acute care. The central tenet of these programmes tends to be policy and guidelines aimed at prescribers. However, rules and guidelines alone may not be sufficient to bring about effective and sustainable optimization of practice. Best practice needs to be positively reinforced by an environment that facilitates and supports optimal prescribing choices, i.e. a 'choice architecture' that makes prudent antibiotic prescribing the path of least resistance. To make prudent antibiotic management an integral part of the behaviour of all healthcare professionals and to bring about quality improvement it is necessary to adopt a whole-system approach. To do this it is necessary first to understand the factors that influence antibiotic management and prescribing.

Details are given of an advanced version of the ring method of chick embryo culture. This ensures good development from early blastoderm stages even when the culturing procedure is interrupted by the extended periods required for collecting matched embryo samples and for preparing antisense treatment. Antisense oligodeoxynucleotide treatment, in short-term incubation before return of blastoderms to their ring cultures, is then described. An alternative, roller-bottle, culture method for continued development after treatment is also described. Criteria for the validity and success of this gene interference method are given. While the text is meant to be of detailed practical help to those inexperienced in embryo culture, a preliminary reading, and familiarity with its sectional (Subheading) structure, is recommended before work is undertaken.

We have targetted the chick gene Flik with antisense oligodeoxynucleotide treatment at gastrular stages, when it is expressed in organiser-derived structures of the midline (K. Patel et al., 1996, Dev. Biol. 178, 327–342). A specific syndrome of deficient axial patterning and holoprosencephaly is produced. Most aspects of this syndrome can be understood as due to attenuation of dorsalising and neural-inducing signals during gastrulation, followed by failure to maintain the later signals from chordamesoderm/neural midline that pattern the mesodermal and neural cross sections during subsequent stages. Anatomical effects are first apparent at early neurula stages and correspond with what might be expected from a reduced counteraction of the ventralising Bone morphogenetic protein (BMP) pathway at the earlier stages, coupled with inadequate Sonic hedgehog (Shh) signalling subsequently. Delay in the clearing of BMP-4 RNA expression from the presumptive neural region at gastrulation is indeed seen, though chordin RNA expression within organiser derivatives remains normal. Subsequently, specific attenuation of chordamesoderm and neural midline Shh expression is observed. Brief preincubation of stage 4 chick blastoderms in supernatant from Xenopus oocytes that have been injected with Flik RNA prolongs and enhances the competence of their peripheral epiblast to respond to neural inductive signals from grafted Hensen's nodes. This effect specifically mimics that recently observed using μg/ml solutions of recombinant Follistatin (D. J. Connolly et al., 1999, Int. J. Dev. Biol., in press), further suggesting that Flik protein might act in vivo by somehow modulating activity of signalling pathways through BMP or other TGFβ-related ligands. We discuss the significance of the observations in relation to recent ideas about neural induction, about possible redundancy in gene action, and about subsequent patterning of the axial cross section, suggesting that a Flik function in autocrine/paracrine maintenance of later midline Shh signalling represents a role of the gene separate from that in primary dorsalisation/neural induction.

The role of the autonomic nervous system in secretory immunoglobulin A (sIgA) responses to laboratory challenge was explored in a study in which sIgA and cardiovascular activity were recorded at rest and during mental arithmetic and paced breathing. These tasks were selected to preferentially engage the sympathetic and parasympathetic nervous systems, respectively. Mental arithmetic elicited a mixed pattern of increased alpha- and beta-adrenergic activity and a reduction in parasympathetic activity; diastolic blood pressure, total peripheral resistance, and systolic blood pressure increased, preejection period shortened, and heart rate variability decreased. In contrast, paced breathing primarily elicited an increase in parasympathetic activity; heart rate variability increased. Mental arithmetic also provoked an increase in sIgA concentration but no change in saliva volume, whereas paced breathing affected neither sIgA concentration nor saliva volume. These data suggest that sIgA responses to laboratory challenges are mediated by sympathetic rather than parasympathetic processes.

The Hospital Pharmacy Initiative was a Department of Health funded programme in England between 2003 and 2006. It has produced a number of benefits that are organizational, educational, professional, clinical and economic. The opportunity to share experiences, identify what works well and collaborate across national boundaries to address a problem that is taxing all governments and NHS acute trusts and causes considerable concern to patients and their families should be a common goal for the UK.

The relationship between the use of antimicrobials and the development of resistance is complex. Considerable variation in the intensity of usage of antimicrobials in outpatient practice has been observed across Europe1 and higher rates of antimicrobial resistance have been noted in high consuming countries, probably related to the higher consumption in southern and eastern Europe than in northern Europe. There is considerable evidence of increasing use of antimicrobials in hospitals worldwide2,3 and concern is constantly highlighted to the extent of sub-optimal and inappropriate prescribing and use.4,5 Macrolide resistance of Streptococcus pneumoniae is becoming a problem, as is Escherichia coli resistance to fluroquinolones.6 In order to address problems of antimicrobial use in general and resistance in particular the Department of Health (DH) established the Specialist Advisory Committee on Antimicrobial Resistance (SACAR) in 2001 as an independent, UK-wide advisory committee to provide expert scientific

Pharmacoeconomics is starting to be employed in strategic therapeutic decision making. Costs associated with antimicrobials included: (i) acquisition costs; (ii) preparation, administration and consumables costs; (iii) monitoring costs; (iv) costs of unwanted drug effects; (v) costs of resistance and therapeutic failures and (vi) costs of duration of stay. Most hospitals have a Drug and Therapeutics Committee but acquisition costs are still the most important economic criterion for acceptance for use, even though medicines only consume between 3 and 5% of total revenue costs, of which antibiotics account for around 15%. In any sequential programme acquisition costs and consumables are immediately realizable. Staff time and monitoring tests are less realizable but require changes in the way budgets are handled. Microbial resistance and risk management are difficult to quantify but are increasingly becoming important in strategic decision-making. The educational needs of health care decision makers in economic need addressing and mechanisms need to be put in place to enable the putative savings reported in the pharmacoeconomic literature to be realized.

In the vertebrate embryo, the lateral compartment of the somite gives rise to muscles of the limb and body wall and is patterned in response to lateral-plate-derived BMP4. Activation of the myogenic program distinctive to the medial somite, i.e. relatively immediate development of the epaxial muscle lineage, requires neutralization of this lateral signal. We have analyzed the properties of molecules likely to play a role in opposing lateral somite specification by BMP4. We propose that the BMP4 antagonist Noggin plays an important role in promoting medial somite patterning in vivo. We demonstrate that Noggin expression in the somite is under the control of a neural-tube-derived factor, whose effect can be mimicked experimentally by Wnt1. Wnt1 is appropriately expressed in the neural tube. Furthermore, we show that Sonic Hedgehog is able to activate ectopic expression of Noggin resulting in the blocking of BMP4 specification of the lateral somite. Our results are consistent with a model in which Noggin activation lies downstream of the SHH and Wnt signaling pathways.