Effectiveness of an emergency nurse practitioner service for adults presenting to rural hospitals with chest pain : Protocol for a multicentre, longitudinal nested cohort study

Introduction Chest pain is common in emergency department (ED) patients and represents a considerable burden for rural health services. Health services reforms to improve access to care need appropriately skilled and supported clinicians in the delivery of safe and effective care, including the use of emergency nurse practitioners (ENPs). Despite increasing use of ENPs, little is known about the safety and quality of the service in the rural ED context. The aims of this study are (1) to examine the safety and quality of the ENP service model in the provision of care in the rural environment and (2) to evaluate the effectiveness of the service in the management of patients presenting with undifferentiated chest pain. Methods and analysis This is the protocol for a prospective longitudinal nested cohort study to compare the effectiveness of ENP service with that of standard care. Adults presenting to three rural EDs in Queensland, Australia with a primary presenting complaint of atraumatic chest pain will be eligible for enrolment. We will measure (1) clinician's use of evidence-based guidelines (2) diagnostic accuracy of ECG interpretation for the management of patients with suspected or confirmed ACS (3) service indicators of waiting times, length-of-stay and did-not-wait rates and (4) clinician's diagnostic accuracy as measured by rates of unplanned representation within 7 days (5) satisfaction with care, (6) quality-of-life and (7) functional status. To assess these outcomes we will use a combination of measures collected from routinely collected data, medical record review and questionnaires (with 30-day follow-up). Ethics and dissemination Queensland Health Human Research Ethics Committee (HREC) has approved this protocol. The results will be published in peer-reviewed scientific journals and presented at one or more scientific conferences.

Towards a consistent definition of a significant delta troponin with z-scores: A way out of chaos?

Aims: We assessed the diagnostic performance of z-scores to define a significant delta cardiac troponin (cTn) in a cohort of patients with well-defined clinical outcomes. Methods: We calculated z-scores, which are dependent on the analytical precision and biological variation, to report changes in cTn. We compared the diagnostic performances of a relative delta (%Δ), actual delta (Δ), and z-scores in 762 emergency department patients with symptoms of suspected acute coronary syndrome. cTn was measured with sensitive cTnI (Beckman Coulter), highly sensitive cTnI (Abbott), and highly sensitive cTnT (Roche) assays. Results: Receiver operating characteristic analysis showed no statistically significant differences in the areas under the curve (AUC) of z-scores and Δ with both superior compared to %Δ for all three assays (p<0.001). The AUCs of z-scores measured with the Abbott hs-cTnI (0.955) and Roche hs-cTnT (0.922) assays were comparable to Beckman Coulter cTnI (0.933) (p=0.272 and 0.640, respectively). The individualized Δ cut-off values that were required to emulate a z-score of 1.96 were: Beckman Coulter cTnI 30 ng/l, Abbott hs-cTnI 20 ng/l, and Roche hs-cTnT 7 ng/l. Conclusions: z-scores allow the use of a single cut-off value at all cTn levels, for both cTnI and cTnT and for sensitive and highly sensitive assays, with comparable diagnostic performances. This strategy of reporting significant changes as z-scores may obviate the need for the empirical development of assay-specific cut-off rules to define significant troponin changes.

Colonoscopy requirements of population screening for colorectal cancer in New Zealand

Aim: To estimate the colonoscopy burden of introducing population screening for colorectal cancer in New Zealand. Methods: Screening for colorectal cancer using biennial immunochemical faecal occult blood tests offered to people aged 50-74 years of age was modelled using population estimates from Statistics New Zealand for 2011-2031. Modelling to determine colonoscopy requirements was based on participation and test positivity rates from published results of screening programmes. Estimates of the number of procedures required for ongoing adenoma surveillance were calculated using screening literature results of adenoma yield, and New Zealand Guidelines for Adenoma Surveillance. Sensitivity analysis was undertaken on key parameters. Results: For a test positivity of 6.4%, biennial screening using immunochemical faecal occult blood testing with a 60% participation rate, would require 18,000 colonoscopies nationally, increasing to 28,000 by 2031. The majority of procedures are direct referrals from a positive FOBT, with surveillance colonoscopy numbers building over time. Conclusion: Colonoscopy requirements for immunochemical faecal occult blood based population screening for colorectal cancer are high. Significant expansion of services is required and careful management of surveillance procedures to ensure timely delivery of initial colonoscopies whilst maintaining symptomatic services. A model re-run informed by data from the screening pilot will allow improved estimates for the New Zealand setting.

Promise and pitfalls of the Immunochip

Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identified moderate proportions of the genetic variants contributing to disease heritability. To provide cost-effective genotyping of common and rare variants to map the remaining heritability and to fine-map established loci, the Immunochip Consortium has developed a 200,000 SNP chip that has been produced in very large numbers for a fraction of the cost of GWAS chips. This chip provides a powerful tool for immunogenetics gene mapping.

An immunodiagnostic assay for quantitation of specific ige to the major pollen allergen component, pas n 1, of the subtropical bahia grass

Background Pollens of the Panicoideae subfamily of grasses including Bahia (Paspalum notatum) are important allergen sources in subtropical regions of the world. An assay for specific IgE to the major molecular allergenic component, Pas n 1, of Bahia grass pollen (BaGP) would have immunodiagnostic utility for patients with pollen allergy in these regions. Methods Biotinylated Pas n 1 purified from BaGP was coated onto streptavidin ImmunoCAPs. Subjects were assessed by clinical history of allergic rhinitis and skin prick test (SPT) to aeroallergens. Serum total, BaGP-specific and Pas n 1-specific IgE were measured. Results: Pas n 1 IgE concentrations were highly correlated with BaGP SPT (r = 0.795, p < 0.0001) and BaGP IgE (r = 0.915, p < 0.0001). At 0.23 kU/l Pas n 1 IgE, the diagnostic sensitivity (92.4%) and specificity (93.1%) for the detection of BaGP allergy was high (area under receiver operator curve 0.960, p < 0.0001). The median concentrations of Pas n 1 IgE in non-Atopic subjects (0.01 kU/l, n = 67) and those with other allergies (0.02 kU/l, n = 59) showed no inter-group difference, whilst grass pollen-Allergic patients with allergic rhinitis showed elevated Pas n 1 IgE (6.71 kU/l, n = 182, p < 0.0001). The inter-Assay coefficient of variation for the BaGP-Allergic serum pool was 6.92%. Conclusions Pas n 1 IgE appears to account for most of the BaGP-specific IgE. This molecular component immunoassay for Pas n 1 IgE has potential utility to improve the sensitivity and accuracy of diagnosis of BaGP allergy for patients in subtropical regions.

Genetics of ankylosing spondylitis and rheumatoid arthritis: Where are we at currently, and how do they compare?

Both ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are common, highly heritable conditions, the pathogenesis of which are incompletely understood. Gene-mapping studies in both conditions have over the last couple of years made major breakthroughs in identifying the mechanisms by which these diseases occur. Considering RA, there is an over-representation of genes involved in TNF signalling and the NFκB pathway that have been shown to influence the disease risk. There is also considerable sharing of susceptibility genes between RA and other autoimmune diseases such as systemic lupus erythematosus, type 1 diabetes, autoimmune thyroid disease and celiac disease, with thus far little overlap with AS. In AS, genes involved in response to IL12/IL23, and in endoplasmic reticulum peptide presentation, have been identified, but a full genomewide association study has not yet been reported.

A suitable method for journal bearing wear measurement

Purpose – Ideally, there is no wear in hydrodynamic lubrication regime. A small amount of wear occurs during start and stop of the machines and the amount of wear is so small that it is difficult to measure with accuracy. Various wear measuring techniques have been used where out-of-roundness was found to be the most reliable method of measuring small wear quantities in journal bearings. This technique was further developed to achieve higher accuracy in measuring small wear quantities. The method proved to be reliable as well as inexpensive. The paper aims to discuss these issues. Design/methodology/approach – In an experimental study, the effect of antiwear additives was studied on journal bearings lubricated with oil containing solid contaminants. The test duration was too long and the wear quantities achieved were too small. To minimise the test duration, short tests of about 90 min duration were conducted and wear was measured recording changes in variety of parameters related to weight, geometry and wear debris. The out-of-roundness was found to be the most effective method. This method was further refined by enlarging the out-of-roundness traces on a photocopier. The method was proved to be reliable and inexpensive. Findings – Study revealed that the most commonly used wear measurement techniques such as weight loss, roughness changes and change in particle count were not adequate for measuring small wear quantities in journal bearings. Out-of-roundness method with some refinements was found to be one of the most reliable methods for measuring small wear quantities in journal bearings working in hydrodynamic lubrication regime. By enlarging the out-of-roundness traces and determining the worn area of the bearing cross-section, weight loss in bearings was calculated, which was repeatable and reliable. Research limitations/implications – This research is a basic in nature where a rudimentary solution has been developed for measuring small wear quantities in rotary devices such as journal bearings. The method requires enlarging traces on a photocopier and determining the shape of the worn area on an out-of-roundness trace on a transparency, which is a simple but a crude method. This may require an automated procedure to determine the weight loss from the out-of-roundness traces directly. This method can be very useful in reducing test duration and measuring wear quantities with higher precision in situations where wear quantities are very small. Practical implications – This research provides a reliable method of measuring wear of circular geometry. The Talyrond equipment used for measuring the change in out-of-roundness due to wear of bearings indicates that this equipment has high potential to be used as a wear measuring device also. Measurement of weight loss from the traces is an enhanced capability of this equipment and this research may lead to the development of a modified version of Talyrond type of equipment for wear measurements in circular machine components. Originality/value – Wear measurement in hydrodynamic bearings requires long duration tests to achieve adequate wear quantities. Out-of-roundness is one of the geometrical parameters that changes with progression of wear in a circular shape components. Thus, out-of-roundness is found to be an effective wear measuring parameter that relates to change in geometry. Method of increasing the sensitivity and enlargement of out-of-roundness traces is original work through which area of worn cross-section can be determined and weight loss can be derived for materials of known density with higher precision.

Genetics of ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that affects the spine and sacroiliac joints. It causes significant disability and is associated with a number of other features including peripheral arthritis, anterior uveitis, psoriasis and inflammatory bowel disease (IBD). Significant progress has been made in the genetics of AS have in the last five years, leading to new treatments in trial, and major leaps in understanding of the aetiopathogenesis of the disease.

Genetic insights into common pathways and complex relationships among iImmune-mediated diseases

Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap. © 2013 Macmillan Publishers Limited. All rights reserved.

Melanopsin mediated post-illumination pupil response in early age-related macular degeneration

Purpose To determine whether melanopsin expressing intrinsically photosensitive Retinal Ganglion Cell (ipRGC) inputs to the pupil light reflex (PLR) are affected in early age-related macular degeneration (AMD). Methods The PLR was measured in 40 participants (20 early AMD and 20 age-matched controls) using a custom-built Maxwellian-view pupillometer. Sinusoidal stimuli (0.5 Hz, 11.9 s duration, 35.6° diameter) were presented to the study eye and the consensual pupil response was measured for stimuli with high melanopsin excitation (464nm; blue) and with low melanopsin excitation (638 nm; red) that biased activation to the outer retina. Two melanopsin PLR metrics were quantified: the Phase Amplitude Percentage (PAP) during the sinusoidal stimulus presentation and the Post-Illumination Pupil Response (PIPR). The PLR during stimulus presentation was analyzed using latency to constriction, transient pupil response and maximum pupil constriction metrics. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves. Results The blue PIPR was significantly less sustained in the early AMD group (p<0.001). The red PIPR was not significantly different between groups (p>0.05). The PAP and blue stimulus constriction amplitude were significantly lower in the early AMD group (p < 0.05). There was no significant difference between groups in the latency or transient amplitude for both stimuli (p>0.05). ROC analysis showed excellent diagnostic accuracy for the blue PIPR metrics (AUC>0.9). Conclusions This is the initial report that the melanopsin controlled PIPR is dysfunctional in early AMD. The non-invasive, objective measurement of the ipRGC controlled PIPR has excellent diagnostic accuracy for early AMD.

The use of a synthetic prostaglandin e1 analogue (misoprostol) as an adjunct to pancreatic enzyme replacement in cystic fibrosis

Eleven cystic fibrosis children (mean age, 9.6 years) were chosen at random to participate in a study to observe the effects of concurrently stimulating gastric/duodenal bicarbonate secretion and inhibiting gastric acid secretion, using a methylated prostaglandin E1 analogue in patients with pancreatic insufficiency and taking pancreatic enzymes. Percentage fat absorption in 3-day stool collections were calculated before and after commencing therapy with misoprostol, 400 μg/day in divided doses. We found a significant reduction in fat output (14.7 ± 11.7 versus 7.5 ± 3.5 g/day, p < 0.05) in the study group as a whole and a significant reduction in steatorrhoeic level as a percentage of fat intake in all of the patients with abnormal base-line collections (23.1% versus 9.2% p < 0.002). We conclude that misoprostol should be considered in cystic fibrosis patients with steatorrhoea as a means of improving nutrient absorption. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Serum immunoreactive cationic trypsinogen: A useful indicator of severe exocrine dysfunction in the paediatric patient without cystic fibrosis

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4·9±4·9 μg/l (mean ±SD), significantly below values in patients with non-pancreatic steatorrhoea (47·0±22·1 μg/l, p<0·001) and 50 control subjects (31·4±7·4 μg/l, p<0·001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0·2-17·0 yr) who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (<-2SD or 16·6 μg/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (≥16·6 μg/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P < .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.

Ultrasound of paediatric appendicitis and its secondary sonographic signs: Providing a more meaningful finding

Sonography is an important clinical tool in diagnosing appendicitis in children as it can obviate both exposure to potentially harmful ionising radiation from computed tomography scans and the need for unnecessary appendicectomies. This review examines the diagnostic accuracy of ultrasound in the identification of acute appendicitis, with a particular focus on the the utility of secondary sonographic signs as an adjunct or corollary to traditionally examined criteria. These secondary signs can be important in cases where the appendix cannot be identified with ultrasound and a more meaningful finding may be made by incorporating the presence or absence of secondary sonographic signs. There is evidence that integrating these secondary signs into the final ultrasound diagnosis can improve the utility of ultrasound in cases where appendicitis is expected, though there remains some conjecture about whether they play a more important role in negative or positive prediction in the absence of an identifiable appendix.

Sonography of paediatric appendicitis and its secondary signs

Sonographic diagnosis of appendicitis in children is an important clinical tool, often obviating the need for potentially harmful ionising radiation from computed tomography (CT) scans and unnecessary appendectomies. Established criteria do not commonly account for the sonographic secondary signs of acute appendicitis as an adjunct or corollary to an identifiably inflamed appendix. If one of, or combinations of these secondary signs are a reliable positive and/or negative indicator of the condition, diagnostic accuracy may be improved. This will be of particular importance in cases where the appendix cannot be easily identified, possibly providing referring clinicians with a less equivocal diagnosis. Acute appendicitis (AA) is the most common emergency presentation requiring surgical intervention among both adults and children. During 2010-11 in Australia 25000 appendicectomies were performed on adults and children, more than double the number of the next most common surgical procedure [1]. Ultrasound has been commonly used to diagnose AA since the 1980s, however the best imaging modality or combination of modalities to accurately and cost-effectively diagnose the condition is still debated. A study by Puylaert advocated ultrasound in all presentations [2], whereas others suggested it only as a first line modality [3–5]. Conversely, York et al state that it is not appropriate as it delays treatment [6]. CT has been shown to more accurately diagnose AA than ultrasound, however its inherent radiation risks warrant cautionary use in children [7]. Improved accuracy in the diagnosis of suspected AA using ultrasound would enable surgeons to make a decision without the need to expose children to the potentially harmful effects of CT. Secondary signs of appendicitis are well established [8], although research into their predictive values has only recently been undertaken [9,10] indicating their potential diagnostic benefit in the absence of an identifiable appendix. The purpose of this review is to examine the history of appendiceal sonography, established sonographic criteria, paediatric specific techniques and the predictive value of secondary signs.