Amiodarone-associated Optic Neuropathy-A Clinical Criteria-based Diagnosis?

Amiodarone-associated optic neuropathy (AAON) is a controversial diagnosis with possible impact on vital cardiac therapy decisions. This retrospective case series aims for application of distinguishing features of AAON versus non-arteritic ischaemic optic neuropathy (NAION): Bilaterality, mode of onset, degree of optic nerve dysfunction, structure of uninvolved disc (unilateral cases), and systemic toxic effects. Applying these criteria to patients with disc swelling under amiodarone, the authors identified four unilateral disc swellings, one with NAION-typical features only and three with one or more NAION-atypical features. All three sequential and six bilateral cases showed one or more NAION-atypical features. The 12 cases highlight the persisting diagnostic dilemma arising from diversity of presentation, lack of plausible pathomechanism, and controversial existence of the entity itself.

Establishment of a protein frequency library and its application in the reliable identification of specific protein interaction partners.

The reliable identification of protein interaction partners and how such interactions change in response to physiological or pathological perturbations is a key goal in most areas of cell biology. Stable isotope labeling with amino acids in cell culture (SILAC)-based mass spectrometry has been shown to provide a powerful strategy for characterizing protein complexes and identifying specific interactions. Here, we show how SILAC can be combined with computational methods drawn from the business intelligence field for multidimensional data analysis to improve the discrimination between specific and nonspecific protein associations and to analyze dynamic protein complexes. A strategy is shown for developing a protein frequency library (PFL) that improves on previous use of static "bead proteomes." The PFL annotates the frequency of detection in co-immunoprecipitation and pulldown experiments for all proteins in the human proteome. It can provide a flexible and objective filter for discriminating between contaminants and specifically bound proteins and can be used to normalize data values and facilitate comparisons between data obtained in separate experiments. The PFL is a dynamic tool that can be filtered for specific experimental parameters to generate a customized library. It will be continuously updated as data from each new experiment are added to the library, thereby progressively enhancing its utility. The application of the PFL to pulldown experiments is especially helpful in identifying either lower abundance or less tightly bound specific components of protein complexes that are otherwise lost among the large, nonspecific background.

NOPdb: Nucleolar Proteome Database--2008 update.

An experimental data handling system has been created as an update to the previous Nucleolar Proteome Database (NOPdb3.0: http://www.lamondlab.com/NOPdb3.0/). This updated system is able to manage large data sets identified by multiple mass spectrometry and has been used to analyse highly purified preparations of human nucleoli from different cell lines. The newly created application includes a dynamic relational database, which is kept up to date by laboratory staff. The data are further annotated with information from specific external sources on the web, including the IPI and Gene Ontology databases. In addition, an Application Programming Interface provides external users with a portal to link into the nucleolar proteome database and hence, gain access to continually updated results. From the initial approximately 700 human proteins identified in the previous iteration of the NOPdb, we have now identified over 50 000 peptides contained in over 4500 human proteins from purified nucleoli, providing enhanced coverage of the nucleolar proteome.

What is eHealth (4): a scoping exercise to map the field.

BACKGROUND: Lack of consensus on the meaning of eHealth has led to uncertainty among academics, policymakers, providers and consumers. This project was commissioned in light of the rising profile of eHealth on the international policy agenda and the emerging UK National Programme for Information Technology (now called Connecting for Health) and related developments in the UK National Health Service. OBJECTIVES: To map the emergence and scope of eHealth as a topic and to identify its place within the wider health informatics field, as part of a larger review of research and expert analysis pertaining to current evidence, best practice and future trends. METHODS: Multiple databases of scientific abstracts were explored in a nonsystematic fashion to assess the presence of eHealth or conceptually related terms within their taxonomies, to identify journals in which articles explicitly referring to eHealth are contained and the topics covered, and to identify published definitions of the concept. The databases were Medline (PubMed), the Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Science Citation Index (SCI), the Social Science Citation Index (SSCI), the Cochrane Database (including Dare, Central, NHS Economic Evaluation Database [NHS EED], Health Technology Assessment [HTA] database, NHS EED bibliographic) and ISTP (now known as ISI proceedings). We used the search query, "Ehealth OR e-health OR e*health". The timeframe searched was 1997-2003, although some analyses contain data emerging subsequent to this period. This was supplemented by iterative searches of Web-based sources, such as commercial and policy reports, research commissioning programmes and electronic news pages. Definitions extracted from both searches were thematically analyzed and compared in order to assess conceptual heterogeneity. RESULTS: The term eHealth only came into use in the year 2000, but has since become widely prevalent. The scope of the topic was not immediately discernable from that of the wider health informatics field, for which over 320000 publications are listed in Medline alone, and it is not explicitly represented within the existing Medical Subject Headings (MeSH) taxonomy. Applying eHealth as narrative search term to multiple databases yielded 387 relevant articles, distributed across 154 different journals, most commonly related to information technology and telemedicine, but extending to such areas as law. Most eHealth articles are represented on Medline. Definitions of eHealth vary with respect to the functions, stakeholders, contexts and theoretical issues targeted. Most encompass a broad range of medical informatics applications either specified (eg, decision support, consumer health information) or presented in more general terms (eg, to manage, arrange or deliver health care). However the majority emphasize the communicative functions of eHealth and specify the use of networked digital technologies, primarily the Internet, thus differentiating eHealth from the field of medical informatics. While some definitions explicitly target health professionals or patients, most encompass applications for all stakeholder groups. The nature of the scientific and broader literature pertaining to eHealth closely reflects these conceptualizations. CONCLUSIONS: We surmise that the field -- as it stands today -- may be characterized by the global definitions suggested by Eysenbach and Eng.

Adoption and perception of electronic clinical communications in Scotland.

OBJECTIVES: To determine the uptake of multiple eHealth facilities enabled by the NHS Scotland Electronic Clinical Communications Implementation Programme (ECCI) and to ascertain primary and secondary care users' perceptions. DESIGN: Prospective monthly measurement of 37 indicators of roll-out and adoption. Retrospective questionnaire survey of users. SETTING: Scottish health board regions. Quantitative implementation indicators were gathered in primary and secondary care across all 16 regions. Questionnaire data were obtained from recorded users in five representative regions (112 general practices, 92 secondary care units). OUTCOME MEASURES: Change in uptake levels of ECCI facilities over a 15-month period. Users' perceptions of benefits, facilitators and barriers. RESULTS: All health boards participated in the monthly data set collection. The response rate to the survey was 62% in primary care and 37% in secondary care. Across Scotland as a whole, the process of implementation was gradual. While there were marked gains in the availability of ECCI facilities over the observation period, rates of adoption lagged behind and varied across alternative facilities. Electronic results were widely used, with most laboratories offering them and around half of general practices receiving them. More modest rates of adoption were observed for e-discharge letters, e-referrals, e-clinic letters and clinical e-mail. E-booking was used very little. Among engaged users responding to the survey, electronic access to test results was the most frequently utilised facility and electronic outpatient booking the least. Perceived benefits of ECCI facilities included convenience, ease of use, time-saving and provision of an audit trail. Perceived barriers included the need to duplicate data entry where new systems were not universally implemented, technological difficulties, time, training and resources. CONCLUSIONS: Significant progress was observed in the implementation of ECCI facilities across Scotland. Users reported that these improved communication and were beneficial, but system reliability, incompatibility and duplication of data hindered more widespread uptake. Data were collected at a transitional phase of the programme. Whilst, among users of ECCI facilities, perceptions of the programme and its potential benefits were generally positive, its full impact will not become evident until the new electronic tools are implemented nationally and have been more fully integrated into normal work routines.

Optic nerve sheath diameter in normal-tension glaucoma patients.

BACKGROUND: To report on the optic nerve sheath diameter (ONSD) in patients with normal-tension glaucoma (NTG) compared with controls without known optic nerve (ON) or intracranial disease. METHODS: In 18 patients with NTG (mean age 64.9 ± 8.9 years; 7 women and 11 men), CT of the orbit was performed. 17 age- and gender-matched patients without ON or intracranial disease, who underwent CT of the orbits for non-ophthalmological reasons, served as controls. The widest intraorbital ONSD in axial sections was measured using a standardised technique. STUDY DESIGN: unmasked. Statistical analysis was performed using an independent two-tailed t Test and the non-parametric Spearman correlation test. RESULTS: ONSD was significantly (p<0.001) increased in NTG patients (right side: mean 7.9 ± 0.9 mm SD; left: 8.0 ± 1.1 mm) compared with controls (right: 6.3 ± 0.5 mm; left: 6.1 ± 0.6 mm). Neither the NTG nor the control group had a significant difference in ONSD between males and females or between right and left sides. CONCLUSIONS: An increased ONSD is generally associated with increased intracranial pressure; however, ONSDs in a group of NTG patients also were significantly increased compared with controls. ON sheath compartmentation and thinning of the ON sheath are two possible explanations for an increase in the ONSD in patients with NTG.

Cerebrospinal fluid dynamics between the basal cisterns and the subarachnoid space of the optic nerve in patients with papilloedema.

AIMS: To determine cerebrospinal fluid (CSF) dynamics between intracranial CSF spaces and CSF in the subarachnoid space (SAS) of optic nerves (ONs) in 10 patients with papilloedema. METHODS: Prospective assessment of 10 patients with papilloedema and two control subjects using CT cisternography and analysis of CSF for the presence of lipocalin-like prostaglandin D synthase (betatrace protein). RESULTS: CT cisternography showed a progressively reduced influx of contrast-loaded CSF from intracranial CSF spaces into the SAS. The lowest concentration of contrast-loaded CSF was found in the region of the ON immediately behind the globe, where the ON sheath was widened (possibly by unfolding) in all patients compared with normal subjects. The concentration of lipocalin-like prostaglandin D synthase differed between the spinal CSF and the CSF in the SAS, with a markedly higher concentration in the SAS. CONCLUSION: The results of this study suggest that CSF turnover in the SAS of the ON is reduced in patients with papilloedema from various causes and that the composition of CSF differs between spinal CSF and that surrounding the ON.

Reducing prescribing errors: can a well-designed electronic system help?

RATIONALE, AIMS AND OBJECTIVES: In this study, the aim was to investigate if an electronic prescribing system designed specifically to reduce errors would lead to fewer errors in prescribing medicines in a secondary care setting. METHOD: The electronic system was compared with paper prescription charts on 16 intensive care patients to assess any change in the number of prescribing errors. RESULTS: The overall level of compliance with nationally accepted standards was significantly higher with the electronic system (91.67%) compared with the paper system (46.73%). Electronically generated prescriptions were found to contain significantly fewer deviations (28 in 329 prescriptions, 8.5%) than the written prescriptions (208 in 408 prescriptions, 51%). CONCLUSION: Taking an interdisciplinary approach to work on the creation of a system designed to minimize the risk of error has resulted in a favoured system that significantly reduces the number of errors made.

What is the frequency of symptomatic mild hypoglycemia in type 1 diabetes in the young?: assessment by novel mobile phone technology and computer-based interviewing.

BACKGROUND: The prevalence of mild hypoglycemia is difficult to document, particularly, in young people with diabetes. The usual method is to ask for subject recall using written 'diaries'. OBJECTIVE: In 2004, we investigated if new technology could be used to ascertain an accurate prevalence of mild hypoglycemia, particularly self-treated. We compared the use of 'text messaging' and computer-based interviewing with the standard diary method. PARTICIPANTS: Thirty-seven participants, aged 7-18 yr, with type 1 diabetes (T1D) for >1-yr duration. METHOD: Open comparison of three systems to collect the data on frequency of hypos (all severity): diary, mobile phone and computer-based interview (CBI), with qualitative analysis of patient feedback. RESULTS: One hundred thirty-two hypos were found over 705 recorded days. All were graded mild or moderate and none severe. Calculated frequency was 5.2 hypos per month: 13.6% subjects had no recorded episode, 36.4% had 1-4, 31.8% 5-9 and 18.2% >10. Mean blood glucose level at the onset of hypoglycemia was 3.0 mmol/L (1.0-5.2). Response rate of occurrence of hypoglycemic episode recorded by three systems is as follows - diary: 24 (65%) of the 37 subjects reported episodes, mobile: 18 (95%) of 19 subjects and CBI: 16 (89%) of 18 subjects. Sixty-five percent of subjects preferred the mobile and 54% of subjects preferred CBI compared with the diary. Fifty-five percent and 30.8% of subjects found the mobile and the CBI, respectively, easiest to fit into their everyday life. CONCLUSIONS: Mobile phone text messaging and CBI are alternatives to written diaries as methods of data collection. Each has its own strengths and weaknesses, but both have the advantage of daily reminders, rapid response and quick data analysis. Using this technology, it was found that the frequency of hypoglycemia was higher (>3 times) than that previously recognized.

Decision-making about mode of delivery after previous caesarean section: development and piloting of two computer-based decision aids.

OBJECTIVE: To develop and pilot two computer-based decision aids to assist women with decision-making about mode of delivery after a previous caesarean section (CS), which could then be evaluated in a randomized-controlled trial. BACKGROUND: Women with a previous CS are faced with a decision between repeat elective CS and vaginal birth after caesarean. Research has shown that women may benefit from access to comprehensive information about the risks and benefits of the delivery options. DESIGN: A qualitative pilot study of two novel decision aids, an information program and a decision analysis program, which were developed by a multidisciplinary research team. PARTICIPANTS AND SETTING: 15 women who had recently given birth and had previously had a CS and 11 pregnant women with a previous CS, recruited from two UK hospitals. Women were interviewed and observed using the decision aids. RESULTS: Participants found both decision aids useful and informative. Most liked the computer-based format. Participants found the utility assessment of the decision analysis program acceptable although some had difficulty completing the tasks required. Following the pilot study improvements were made to expand the program content, the decision analysis program was accompanied by a training session and a website version of the information program was developed to allow repeat access. CONCLUSIONS: This pilot study was an essential step in the design of the decision aids and in establishing their acceptability and feasibility. In general, participating women viewed the decision aids as a welcome addition to routine antenatal care. A randomized trial has been conducted to establish the effectiveness and cost-effectiveness of the decision aids.

Meta-analysis: cardiovascular events associated with nonsteroidal anti-inflammatory drugs.

PURPOSE: We performed a meta-analysis of randomized controlled trials to assess the effect of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) on cardiovascular events in trials of joint disease and Alzheimer's disease. METHODS: We performed comprehensive searches of MEDLINE, EMBASE, CINAHL and Cochrane databases from 1966 to July 2005, and references of identified articles and reviews. We included randomized placebo-controlled trials of at least 6 weeks duration that evaluated nonselective NSAIDs in trials of joint disease or Alzheimer's disease, and reported at least one cardiovascular event or death. The outcome measured was the composite of death, myocardial infarction or cerebrovascular accident, with the pooled results reported as odds ratios (OR). Subgroup analyses evaluated the difference between trials of joint disease and Alzheimer's disease, and for naproxen and non-naproxen NSAIDs. RESULTS: Pooled data from 13 trials with 7718 participants showed that nonselective NSAIDs had no significant effect on cardiovascular events (OR 1.3; 95% confidence interval [CI], 0.8 to 2.1). No significant effect was seen for joint disease trials (OR 0.6; 95% CI, 0.2 to 1.7) or Alzheimer disease trials (OR 1.6; 95% CI, 0.9 to 2.7). There was no significant difference in results for naproxen and non-naproxen NSAIDs. CONCLUSION: Nonselective NSAIDs have no significant effect on cardiovascular events or death in trials of joint disease and Alzheimer disease, but a small adverse effect could not be excluded. An indication for risk was present in trials of Alzheimer's disease but not in joint disease trials. There was no significant adverse or cardioprotective effect of naproxen.