Prevalence and Causes of Prescribing ErrorsL The PRescribing Outcomes for Trainee Doctors Engaged in Clinical Training (PROTECT) Study

Objectives: Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing.

Method: A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors’ self-efficacy were established.

Results: 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p,0.001), surgical (p = ,0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p,0.001), a greater number of prescribed medicines (p,0.001) and the months December and June (p,0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen.

Conclusions: Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.

Temper outbursts in Prader-Willi syndrome: causes, behavioural and emotional sequence and responses by carers

Background: Temper outbursts are common in Prader-Willi syndrome but rarely described in detail. This study investigated the phenomenology of temper outbursts in terms of antecedents, sequence of behaviours and emotions and intervention strategies used.

Method: A semi-structured interview about temper outbursts was conducted with the main carers of seven children (9.5 to 16.7 years) and seven adults (24.7 to 47.10 years) with Prader-Willi syndrome (10 male, 4 female). Reliability and validity of the interview results was established.

Results: Various setting events increased and reduced the likelihood of temper outbursts. The most common antecedent was a change to routine or expectation. There were marked similarities in the sequence of behaviours and emotions during temper outbursts, with anger rising quickly followed by expressions of remorse and distress at the end of an outburst.

Discussion: The sequence of behaviours and emotions within outbursts was similar to that described in temper tantrums in typical development. Cognitive and emotional processes are likely to be important in the understanding of temper outbursts with implications for early intervention.

Identification of the Flagellin Glycosylation System in Burkholderia cenocepacia and the Contribution of Glycosylated Flagellin to Evasion of Human Innate Immune Responses

Burkholderia cenocepacia is an opportunistic pathogen threatening patients with cystic fibrosis. Flagella are required for biofilm formation, as well as adhesion to and invasion of epithelial cells. Recognition of flagellin via the Toll-like receptor 5 (TLR5) contributes to exacerbate B. cenocepacia-induced lung epithelial inflammatory responses. In this study, we report that B. cenocepacia flagellin is glycosylated on at least 10 different sites with a single sugar, 4,6-dideoxy-4-(3-hydroxybutanoylamino)-d-glucose. We have identified key genes that are required for flagellin glycosylation, including a predicted glycosyltransferase gene that is linked to the flagellin biosynthesis cluster and a putative acetyltransferase gene located within the O-antigen lipopolysaccharide cluster. Another O-antigen cluster gene, rmlB, which is required for flagellin glycan and O-antigen biosynthesis, was essential for bacterial viability, uncovering a novel target against Burkholderia infections. Using glycosylated and nonglycosylated purified flagellin and a cell reporter system to assess TLR5-mediated responses, we also show that the presence of glycan in flagellin significantly impairs the inflammatory response of epithelial cells. We therefore suggest that flagellin glycosylation reduces recognition of flagellin by host TLR5, providing an evasive strategy to infecting bacteria.

Predicting the past: Understanding the causes of bank distress in the Netherlands in the 1920s

Why do some banks fail in financial crises while others survive? This article answers this question by analysing the effect of the Dutch financial crisis of the 1920s on 142 banks, of which 33 failed. We find that choices of balance sheet composition and product market strategy made in the lead-up to the crisis had a significant impact on banks’ subsequent chances of experiencing distress. We document that high-risk banks – those operating highly-leveraged portfolios and attracting large quantities of deposits – were more likely to fail. Branching and international activities also increased banks’ default probabilities. We measure the effects of board interlocks, which have been characterized in the extant literature as contributing to the Dutch crisis. We find that boards mattered: failing banks had smaller boards, shared directors with smaller and very profitable banks and had a lower concentration of interlocking directorates in non-financial firms.

Epstein-Barr Virus Large Tegument Protein BPLF1 Contributes to Innate Immune Evasion through Interference with Toll-Like Receptor Signaling

Viral infection triggers an early host response through activation of pattern recognition receptors, including Toll-like receptors (TLR). TLR signaling cascades induce production of type I interferons and proinflammatory cytokines involved in establishing an anti-viral state as well as in orchestrating ensuing adaptive immunity. To allow infection, replication, and persistence, (herpes)viruses employ ingenious strategies to evade host immunity. The human gamma-herpesvirus Epstein-Barr virus (EBV) is a large, enveloped DNA virus persistently carried by more than 90% of adults worldwide. It is the causative agent of infectious mononucleosis and is associated with several malignant tumors. EBV activates TLRs, including TLR2, TLR3, and TLR9. Interestingly, both the expression of and signaling by TLRs is attenuated during productive EBV infection. Ubiquitination plays an important role in regulating TLR signaling and is controlled by ubiquitin ligases and deubiquitinases (DUBs). The EBV genome encodes three proteins reported to exert in vitro deubiquitinase activity. Using active site-directed probes, we show that one of these putative DUBs, the conserved herpesvirus large tegument protein BPLF1, acts as a functional DUB in EBV-producing B cells. The BPLF1 enzyme is expressed during the late phase of lytic EBV infection and is incorporated into viral particles. The N-terminal part of the large BPLF1 protein contains the catalytic site for DUB activity and suppresses TLR-mediated activation of NF-κB at, or downstream of, the TRAF6 signaling intermediate. A catalytically inactive mutant of this EBV protein did not reduce NF-κB activation, indicating that DUB activity is essential for attenuating TLR signal transduction. Our combined results show that EBV employs deubiquitination of signaling intermediates in the TLR cascade as a mechanism to counteract innate anti-viral immunity of infected hosts.

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

Introduction

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

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

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

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

National trends in main causes of hospitalization: a multi-cohort register study of the Finnish working-age population, 1976-2010

Principal Findings: Over the period of 35 years, the risk of hospitalization for cardiovascular diseases and respiratory diseases decreased. Hospitalization for musculoskeletal diseases increased whereas mental and behavioral hospitalizations slightly decreased. The risk of cancer hospitalization decreased marginally in men, whereas in women an upward trend was observed.

Conclusions/Significance: A considerable health transition related to hospitalizations and a shift in the utilization of health care services of working-age men and women took place in Finland between 1976 and 2010.

Background: The health transition theory argues that societal changes produce proportional changes in causes of disability and death. The aim of this study was to identify long-term changes in main causes of hospitalization in working-age population within a nation that has experienced considerable societal change.

Methodology: National trends in all-cause hospitalization and hospitalizations for the five main diagnostic categories were investigated in the data obtained from the Finnish Hospital Discharge Register. The seven-cohort sample covered the period from 1976 to 2010 and consisted of 3,769,356 randomly selected Finnish residents, each cohort representing 25% sample of population aged 18 to 64 years.

Material Waste in the Northern Ireland Construction Industry: On-Site Management Causes and Methods of Prevention

The construction industry in Northern Ireland is one of the major contributors of construction waste to landfill each year. The aim of this research paper is to identify the core on-site management causes of material waste on construction sites in Northern Ireland and to illustrate various methods of prevention which can be adopted. The research begins with a detailed literature review and is complemented with the conduction of semi-structured interviews with 6 professionals who are experienced and active within the Northern Ireland construction industry. Following on from the literature review and interviews analysis, a questionnaire survey is developed to obtain further information in relation to the subject area. The questionnaire is based on the key findings of the previous stages to direct the research towards the most influential factors. The analysis of the survey responses reveals that the core causes of waste generation include a rushed program, poor handling and on-site damage of materials, while the principal methods of prevention emerge as the adequate storage, the reuse of material on-site and efficient material ordering. Furthermore, the role of the professional background in the shaping of perceptions relevant to waste management is also investigated and significant differences are identified. The findings of this research are beneficial for the industry as they enhance the understanding of construction waste generation causes and highlight the practices required to reduce waste on-site in the context of sustainable development.

Common causes and current guidelines

Chronic cough is a common and disabling symptom. Recent guidelines have attempted to provide direction in the clinical management of cough in both primary and secondary care. They have also provided a critical review of the available literature and identified gaps in current knowledge. Despite this they have been criticized for a reliance on a low quality evidence base. In this review, we summarize the current consensus on the clinical management of chronic cough and attempt to rationalize this based on recent evidence. We have also provided an overview of the likely pathophysiological mechanisms responsible for cough and highlighted areas, where knowledge deficits exist and suggest directions for future research. Such progress will be critical in the search for new and effective treatments for cough.

New insights into the causes of human illness due to consumption of azaspiracid contaminated shellfish

Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of Irish coastline was selected and shellfish were sampled and tested for AZA using mass spectrometry. An outbreak was identified in 2010 and samples collected before and after the contamination episode were compared for their metabolite profile using high resolution mass spectrometry. Twenty eight ions were identified at higher concentration in the contaminated samples. Stringent bioinformatic analysis revealed putative identifications for seven compounds including, glutarylcarnitine, a glutaric acid metabolite. Glutaric acid, the parent compound linked with human neurological manifestations was subjected to toxicological investigations but was found to have no specific effect on the sodium channel (as was the case with AZA). However in combination, glutaric acid (1mM) and azaspiracid (50nM) inhibited the activity of the sodium channel by over 50%. Glutaric acid was subsequently detected in all shellfish employed in the study. For the first time a viable mechanism for how AZA manifests itself as a toxin is presented.

Causes and five-year incidence of blindness and visual impairment in urban southern China:The Liwan Eye Study

PURPOSE. We determined the causes and five-year incidence of blindness and visual impairment (VI) in an adult, urban Chinese population. METHODS. Participants underwent a comprehensive eye examination at baseline in 2003 and then five years later. The World Health Organization (WHO) and United States (US) definitions were used to define incident blindness (WHO visual acuity [VA] < 20/400 in the better-seeing eye, US VA ≤ 20/200) and incident VI (WHO VA < 20/60-20/400, US VA < 20/40->20/200). RESULTS. Among 1405 baseline participants, 924 (75%) of 1232 survivors (87.7%) participated in the 5-year follow-up. The incidences of VI and blindness were 5.38% (95% confidence interval [CI] 3.99% ~ 7.07%) and 0.33% (95% CI 0.07% ~ 0.95%), respectively, based on the WHO definition, and 9.85% (95% CI 7.96% ~ 12.0%) and 1.42% (95% CI 0.76% ~ 2.41%), respectively, based on the US definition. Incidence of blindness and VI (WHO definition) increased significantly with older age (P < 0.001) and poorer baseline presenting VA in the worse-seeing eye (P < 0.001). The leading cause of best-corrected VI (WHO definition) was cataract (64.6%), whereas the main causes of presenting VI were refractive error (40.4%) and cataract (38.4%). CONCLUSIONS. The incidence of VI in urban Southern China is high. The major causes are unoperated cataract and undercorrected refractive error, reflecting the need for better surgical and refractive care, even in this urban setting. © 2013 The Association for Research in Vision and Ophthalmology, Inc.