Clinical and experimental links between diabetes and glaucoma

Glaucoma is a leading cause of blindness. It is a multifactorial condition, the risk factors for which are increasingly well defined from large-scale epidemiological studies. One risk factor that remains controversial is the presence of diabetes. It has been proposed that diabetic eyes are at greater risk of injury from external stressors, such as elevated intraocular pressure. Alternatively, diabetes may cause ganglion cell loss, which becomes additive to a glaucomatous ganglion cell injury. Several clinical trials have considered whether a link exists between diabetes and glaucoma. In this review, we outline these studies and consider the causes for their lack of concordant findings. We also review the biochemical and cellular similarities between the two conditions. Moreover, we review the available literature that attempts to answer the question of whether the presence of diabetes increases the risk of developing glaucoma. At present, laboratory studies provide robust evidence for an association between diabetes and glaucoma.

Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus

ObjectiveThe objective of this paper is to elucidate the role of specific cytokines in lupus (SLE) arthritis.MethodsFifty SLE and 40 RA patients had an ultrasound (US) scan of their hand as per standardized protocols. US scores were expressed per joint and as a total 'US activity' score, (sum of power Doppler (PD) and grey-scale synovial hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA-SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine kits, R & D).ResultsOn the basis of the US results SLE patients were divided into three groups: erosive arthritis (n?=?20), non-erosive arthritis (n?=?18) and those with a normal US scan (n?=?12). Across the SLE groups plasma IL-6 levels correlated with CRP (p?

Comparative evaluation of 2,3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8) rapid colorimetric assays for antimicrobial susceptibility testing of staphylococci and ESBL-producing clinical isolates

A new generation of water soluble tetrazolium salts have recently become available and in this study we compared a colorimetric assay developed using one of these salts, 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8), with a previously developed 2,3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) colorimetric assay to determine which agent is most suitable for use as a colorimetric indicator in susceptibility testing. The MICs of 6 antibiotics were determined for 33 staphylococci using both colorimetric assays and compared with those obtained using the British Society for Antimicrobial Chemotherapy reference broth microdilution method. Absolute categorical agreement between the reference and test methods ranged from 79% (cefuroxime) to 100% (vancomycin) for both assays. No minor or major errors occurred using either assay with very major errors ranging from zero (vancomycin) to seven (cefuroxime). Analysis of the distribution of differences in the log2 dilution MIC results revealed overall agreement, within the accuracy limits of the standard test (± 1 log2 dilution), using the XTT and WST-8 assays of 98% and 88%, respectively. Further studies on 31 ESBL-producing isolates were performed using the XTT method with absolute categorical agreement ranging from 87% (nitrofurantoin) to 100% (ofloxacin and meropenem). No errors were noted for either ofloxacin or meropenem with overall agreement of 91%. The data suggests that XTT is more reliable and accurate than WST-8 for use in a rapid antimicrobial susceptibility test.

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.

Improvement in clinical step and shoot intensity modulated radiation therapy delivery accuracy on an integrated linear accelerator control system

Purpose: The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac.

Methods and Materials: Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan.

Results: Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam.

Conclusions: The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac. © 2014.

Variation of clinical outcomes used in glaucoma randomised controlled trials:a systematic review

Purpose: In randomised clinical trials (RCTs) the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. The purpose of this review is to identify different clinical outcomes reported in glaucoma trials.

Methods We conducted a systematic review of glaucoma RCTs. A sample or selection of glaucoma trials were included bounded by a time frame (between 2006 and March 2012). Only studies in English language were considered. All clinical measured and reported outcomes were included. The possible variations of clinical outcomes were defined prior to data analysis. Information on reported clinical outcomes was tabulated and analysed using descriptive statistics. Other data recorded included type of intervention and glaucoma, duration of the study, defined primary outcomes, and outcomes used for sample size calculation, if nominated.

Results The search strategy identified 4323 potentially relevant abstracts. There were 315 publications retrieved, of which 233 RCTs were included. A total of 967 clinical measures were reported. There were large variations in the definitions used to describe different outcomes and their measures. Intraocular pressure was the most commonly reported outcome (used in 201 RCTs, 86%) with a total of 422 measures (44%). Safety outcomes were commonly reported in 145 RCTs (62%) whereas visual field outcomes were used in 38 RCTs (16%).

Conclusions There is a large variation in the reporting of clinical outcomes in glaucoma RCTs. This lack of standardisation may impair the ability to evaluate the evidence of glaucoma interventions.

Offshoring Clinical Trials: The Mutable Ethics, Weak Protections and Vulnerable Subjects of EU Law

In this paper I engage with science and technology studies work on pharmaceuticalisation to explore how European Union (EU) law helps to produce and support the preference for pharmaceutical responses in public health governance, while authorising the production of vulnerable subjects through the growing off-shoring of clinical trials. Drawing on the analysis of legal and policy documents, I demonstrate how EU law allows and legitimates the use of data procured from vulnerable subjects abroad for market authorisation and corporate profitability at home. This is possible because the EU has (de)selected international ethical frameworks in order to support the continued and growing use of clinical trials data from abroad. This has helped to stimulate the revision of international ethical frameworks in light of market needs, inscribing EU public health law within specific politics (that often remained obscured by the joint workings of legal and technological discourses). I suggest that law operates as part of a broader ‘technology’ – encompassing ethics and human rights discourses – that functions to optimise life through resort to market reasoning. Law is thereby reoriented, instrumentalised and deployed as part of a broader project aimed at (re)defining and limiting the boundaries of the EU's responsibility for public health, including the broader social production of public health problems and the unequal global order that the EU represents and helps to depoliticise and perpetuate. Overall, this limits the EU's responsibility and accountability for these failures, as well as another: the weak and mutable protections and insecure legacies for vulnerable trial subjects abroad.

A systematic review evaluating the impact of online or blended learning vs. face-to-face learning of clinical skills in undergraduate nurse education.

Aim: To determine whether the use of an online or blended learning paradigm has the potential to enhance the teaching of clinical skills in undergraduate nursing.

Background: The need to adequately support and develop students in clinical skills is now arguably more important than previously considered due to reductions in practice opportunities. Online and blended teaching methods are being developed to try and meet this requirement, but knowledge about their effectiveness in teaching clinical skills is limited.

Design: Mixed methods systematic review, which follows the Joanna Briggs Institute User guide version 5.

Data Sources: Computerized searches of five databases were undertaken for the period 1995-August 2013.

Review Methods: Critical appraisal and data extraction were undertaken using Joanna Briggs Institute tools for experimental/observational studies and interpretative and critical research. A narrative synthesis was used to report results.

Results: Nineteen published papers were identified. Seventeen papers reported on online approaches and only two papers reported on a blended approach. The synthesis of findings focused on the following four areas: performance/clinical skill, knowledge, self-efficacy/clinical confidence and user experience/satisfaction. The e-learning interventions used varied throughout all the studies.

Conclusion: The available evidence suggests that online learning for teaching clinical skills is no less effective than traditional means. Highlighted by this review is the lack of available evidence on the implementation of a blended learning approach to teaching clinical skills in undergraduate nurse education. Further research is required to assess the effectiveness of this teaching methodology.

History taking and clinical examination skills from a stoma nurse’s perspective

Comprehensive history-taking and clinical examination skills are examples of role development for a stoma care nurse specialist. Comprehensive history-taking is a thorough exploration of a patient's presenting complaint and the gathering of subjective information, while clinical examination is the gathering of objective information from a head-to-toe assessment or a focused assessment of a particular body system. This paper demonstrates the application of comprehensive history-taking and gastrointestinal clinical examination skills by the stoma care nurse in a clinical community setting, and explores their advantages and disadvantages in stoma care practice.

Anaesthetic nurse specialist role: leading and facilitation in clinical practice

Leadership and its effectiveness is becoming more prevalent within the nursing profession with anaesthetic nurse specialists showing their ability to lead, inspire and motivate others to work towards a shared vision in the rapidly changing peri-anaesthesia environment. Anaesthetic nurse specialists must therefore be aware of their personal leadership skills and continually develop these within clinical practice. They are also well placed regarding the facilitation of learning.

Central venous catheterization - An anatomical review of a clinical skill - Part 1: Subclavian vein via the infraclavicular approach.

The safe and successful performance of a central venous catheterization (CVC) requires a specific knowledge of anatomy in addition to a working knowledge. Misunderstanding the anatomy may result in failure or complications. This review aims to aid understanding of the anatomical framework, pitfalls, and complications of CVC of the subclavian (SCV). CVC is common practice amongst surgeons, anesthesiologists, and emergency room physicians during the preparations for major surgical procedures such as open-heart surgery, as well as, for intensive care monitoring and rapid restoration of blood volume. Associated with this technique are certain anatomical pitfalls and complications that can be successfully avoided if one possesses a thorough knowledge of the contraindications, regional anatomy, and rationale of the technique.

Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients

Aim: To determine if serum pigment epithelium-derived factor (PEDF) levels in Type 2 diabetes are related to vascular risk factors and renal function. Methods: PEDF was quantified by ELISA in a cross-sectional study of 857 male Veterans Affairs Diabetes Trial (VADT) subjects, and associations with cardiovascular risk factors and renal function were determined. In a subset (n = 246) in whom serum was obtained early in the VADT (2.0 ± 0.3 years post-randomization), PEDF was related to longitudinal changes in renal function over 3.1 years. Results: Cross-sectional study: In multivariate regression models, PEDF was positively associated with serum triglycerides, waist-to-hip ratio, serum creatinine, use of ACE inhibitors or angiotensin receptor blockers, and use of lipid-lowering agents; it was negatively associated with HDL-C (all p < 0.05). Longitudinal study: PEDF was not associated with changes in renal function over 3.1 years (p > 0.09). Conclusions: Serum PEDF in Type 2 diabetic men was cross-sectionally associated with dyslipidemia, body habitus, use of common drugs for blood pressure and dyslipidemia, and indices of renal function; however, PEDF was not associated with renal decline over 3.1 years.

How Outcomes Are Defined in Clinical Trials of Mechanically Ventilated Adults and Children

Systematic reviews have considerable potential to provide evidence-based data to aid clinical decision-making. However, there is growing recognition that trials involving mechanical ventilation lack consistency in the definition and measurement of ventilation outcomes, creating difficulties in combining data for meta-analyses. To address the inconsistency in outcome definitions, international standards for trial registration and clinical trial protocols published recommendations, effectively setting the “gold standard” for reporting trial outcomes. In this Critical Care Perspective, we review the problems resulting from inconsistent outcome definitions and inconsistent reporting of outcomes (outcome sets). We present data highlighting the variability of the most commonly reported ventilation outcome definitions. Ventilation outcomes reported in trials over the last 6 years typically fall into four domains: measures of ventilator dependence; adverse outcomes; mortality; and resource use. We highlight the need, first, for agreement on outcome definitions and, second, for a minimum core outcome set for trials involving mechanical ventilation. A minimum core outcome set would not restrict trialists from measuring additional outcomes, but would overcome problems of variability in outcome selection, measurement, and reporting, thereby enhancing comparisons across trials.

Lung clearance index: Evidence for use in clinical trials in cystic fibrosis

The ECFS-CTN Standardisation Committee has undertaken this review of lung clearance index as part of the group's work on evaluation of clinical endpoints with regard to their use in multicentre clinical trials in CF. The aims were 1) to review the literature on reliability, validity and responsiveness of LCI in patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3) to gain consensus on answers to key questions regarding the promotion of LCI to surrogate endpoint status. It was concluded that LCI has an attractive feasibility and clinimetric properties profile and is particularly indicated for multicentre trials in young children with CF and patients with early or mild CF lung disease. This is the first article to collate the literature in this manner and support the use of LCI in clinical trials in CF.