EGFR expression : associations with outcome and clinicopathological variables in malignant pleural mesothelioma

Malignant mesothelioma (MM) is a fatal tumour of increasing incidence which is related to asbestos exposure. This work evaluated expression in MM of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry in 168 tumour sections and its correlations with clinicopathological and biological factors. The microvessel density (MVD) was derived from CD34 immunostained sections. Hematoxylin and eosin stained sections were examined for intratumoural necrosis. COX-2 protein expression was evaluated with semi-quantitative Western blotting of homogenised tumour supernatants (n = 45). EGFR expression was correlated with survival by Kaplan-Meier and log rank analysis. Univariate and multivariate Cox proportional hazards models were used to compare the effects of EGFR with clinicopathological and biological prognostic factors and prognostic scoring systems. EGFR expression was identified in 74 cases (44%) and correlated with epithelioid cell type (p < 0.0001), good performance status (p < 0.0001), the absence of chest pain (p < 0.0001) and the presence of TN (p = 0.004), but not MVD or COX-2. EGFR expression was a good prognostic factor in univariate analysis (p = 0.01). Independent indicators of poor prognosis in multivariate analysis were non-epithelioid cell type (p = 0.0001), weight loss, performance status and WBC > 8.3 × 10 9 L -1. EGFR status was not an independent prognostic factor. EGFR expression in MM correlates with epithelioid histology and TN. EGFR may be a target for selective therapies in MM. © 2006 Elsevier Ireland Ltd. All rights reserved.

Process mining for clinical processes: A comparative analysis of four Australian hospitals

Business process analysis and process mining, particularly within the health care domain, remain under-utilised. Applied research that employs such techniques to routinely collected, health care data enables stakeholders to empirically investigate care as it is delivered by different health providers. However, cross-organisational mining and the comparative analysis of processes present a set of unique challenges in terms of ensuring population and activity comparability, visualising the mined models and interpreting the results. Without addressing these issues, health providers will find it difficult to use process mining insights, and the potential benefits of evidence-based process improvement within health will remain unrealised. In this paper, we present a brief introduction on the nature of health care processes; a review of the process mining in health literature; and a case study conducted to explore and learn how health care data, and cross-organisational comparisons with process mining techniques may be approached. The case study applies process mining techniques to administrative and clinical data for patients who present with chest pain symptoms at one of four public hospitals in South Australia. We demonstrate an approach that provides detailed insights into clinical (quality of patient health) and fiscal (hospital budget) pressures in health care practice. We conclude by discussing the key lessons learned from our experience in conducting business process analysis and process mining based on the data from four different hospitals.

Pulmonary embolism in the emergency department : a Singaporean nursing case review

Introduction The presentation of pulmonary embolism to the emergency department (ED) can prove challenging because of the myriad of potential disease processes that mimic its signs and symptoms. The incidence of pulmonary embolism and indeed the mortality associated with it is relatively high. Early diagnosis and treatment is crucial in off-setting the potential deleterious effects associated with this condition. The aim of this article is to present a nursing case review of a patient presenting to the ED with a diagnosis of pulmonary embolism. Method We chose to use a case review to highlight the nursing and medical care that was provided for a patient who presented to the emergency department acutely with dyspnoea, chest pain and pyrexia. The use of case reviews are useful in reporting unusual or rare cases and this format is typically seen more in medicine than in nursing. They can naturally take one of two formats—a single case report or a series of case reports; in this case we opted to report on a single case. Discussion The gentleman in question was an ambulance admissionto the ED with a three day history of chest pain, shortness of breath and one episode of syncope which brought him to the ED. Over the course of his admission a variety of treatment modalities were used successfully to alleviate the problem. More notable from a nursing perspective was the use of diagnostic tools as an interpretation to guide his care and provide a platform from which a deeper understanding and appreciation of the intricacies the critically ill patient often presents. Conclusion We found the use of case review very enlightening in understanding the disease process and the decision-making that accompanies this. Whilst our patient was successfully rehabilitated home, we learnt a lot from the experience which has been most beneficial in supporting our understanding of pulmonary embolism.

Do sex and atopy influence cough outcome measurements in children?

Background Despite the commonality of cough and its burden, there are no published data on the relationship between atopy or sex on objectively measured cough frequency or subjective cough scores in children. In 202 children with and without cough, we determined the effect of sex and atopy on validated cough outcome measurements (cough receptor sensitivity [CRS], objective cough counts, and cough scores). We hypothesized that in contrast to adult data, sex does not influence cough outcome measures, and atopy is not a determinant of these cough measurements. Methods We combined data from four previous studies. Atopy (skin prick test), the concentration of capsaicin causing two and five or more coughs (C2 and C5, respectively), objectively measured cough frequency, and cough scores were determined and their relationship explored. The children’s (93 girls, 109 boys) mean age was 10.6 years (SD 2.9), and 56% had atopy. Results In multivariate analysis, CRS was influenced by age (C2 coefficient, 5.9; P = .034; C5 coefficient, 29.1; P = .0001). Atopy and sex did not significantly influence any of the cough outcomes (cough counts, C2, C5, cough score) in control subjects and children with cough. Conclusions Atopy does not influence important cough outcome measures in children with and without chronic cough. However, age, but not sex, influences CRS in children. Unlike adult data, sex does not affect objective counts or cough score in children with and without chronic cough. Studies on cough in children should be age matched, but matching for atopic status and sex is less important.

Measuring patient flow variations : a cross-organisational process mining approach

Variations that exist in the treatment of patients (with similar symptoms) across different hospitals do substantially impact the quality and costs of healthcare. Consequently, it is important to understand the similarities and differences between the practices across different hospitals. This paper presents a case study on the application of process mining techniques to measure and quantify the differences in the treatment of patients presenting with chest pain symptoms across four South Australian hospitals. Our case study focuses on cross-organisational benchmarking of processes and their performance. Techniques such as clustering, process discovery, performance analysis, and scientific workflows were applied to facilitate such comparative analyses. Lessons learned in overcoming unique challenges in cross-organisational process mining, such as ensuring population comparability, data granularity comparability, and experimental repeatability are also presented.

A multicenter study on chronic cough in children : burden and etiologies based on a standardized management pathway

Background While the burden of chronic cough in children has been documented, etiologic factors across multiple settings and age have not been described. In children with chronic cough, we aimed (1) to evaluate the burden and etiologies using a standard management pathway in various settings, and (2) to determine the influence of age and setting on disease burden and etiologies and etiology on disease burden. We hypothesized that the etiology, but not the burden, of chronic cough in children is dependent on the clinical setting and age. Methods From five major hospitals and three rural-remote clinics, 346 children (mean age 4.5 years) newly referred with chronic cough (> 4 weeks) were prospectively managed in accordance with an evidence-based cough algorithm. We used a priori definitions, timeframes, and validated outcome measures (parent-proxy cough-specific quality of life [PC-QOL], a generic QOL [pediatric quality of life (PedsQL)], and cough diary). Results The burden of chronic cough (PC-QOL, cough duration) significantly differed between settings (P = .014, 0.021, respectively), but was not influenced by age or etiology. PC-QOL and PedsQL did not correlate with age. The frequency of etiologies was significantly different in dissimilar settings (P = .0001); 17.6% of children had a serious underlying diagnosis (bronchiectasis, aspiration, cystic fibrosis). Except for protracted bacterial bronchitis, the frequency of other common diagnoses (asthma, bronchiectasis, resolved without specific-diagnosis) was similar across age categories. Conclusions The high burden of cough is independent of children’s age and etiology but dependent on clinical setting. Irrespective of setting and age, children with chronic cough should be carefully evaluated and child-specific evidence-based algorithms used.

The radiological diagnosis of pneumonia in children

Despite the importance of paediatric pneumonia as a cause of short and long-term morbidity and mortality worldwide, a reliable gold standard for its diagnosis remains elusive. The utility of clinical, microbiological and radiological diagnostic approaches varies widely within and between populations and is heavily dependent on the expertise and resources available in various settings. Here we review the role of radiology in the diagnosis of paediatric pneumonia. Chest radiographs (CXRs) are the most widely employed test, however, they are not indicated in ambulatory settings, cannot distinguish between viral and bacterial infections and have a limited role in the ongoing management of disease. A standardised definition of alveolar pneumonia on a CXR exists for epidemiological studies targeting bacterial pneumonias but it should not be extrapolated to clinical settings. Radiography, computed tomography and to a lesser extent ultrasonography and magnetic resonance imaging play an important role in complicated pneumonias but there are limitations that preclude their use as routine diagnostic tools. Large population-based studies are needed in different populations to address many of the knowledge gaps in the radiological diagnosis of pneumonia in children, however, the feasibility of such studies is an important barrier.

Effectiveness of electrocardiographic guidance in CVAD tip placement

Background International standard practice for the correct confirmation of the central venous access device is the chest X-ray. The intracavitary electrocardiogram-based insertion method is radiation-free, and allows real-time placement verification, providing immediate treatment and reduced requirement for post-procedural repositioning. Methods Relevant databases were searched for prospective randomised controlled trials (RCTs) or quasi RCTs that compared the effectiveness of electrocardiogram-guided catheter tip positioning with placement using surface-anatomy-guided insertion plus chest X-ray confirmation. The primary outcome was accurate catheter tip placement. Secondary outcomes included complications, patient satisfaction and costs. Results Five studies involving 729 participants were included. Electrocardiogram-guided insertion was more accurate than surface anatomy guided insertion (odds ratio: 8.3; 95% confidence interval (CI) 1.38; 50.07; p=0.02). There was a lack of reporting on complications, patient satisfaction and costs. Conclusion The evidence suggests that intracavitary electrocardiogram-based positioning is superior to surface-anatomy-guided positioning of central venous access devices, leading to significantly more successful placements. This technique could potentially remove the requirement for post-procedural chest X-ray, especially during peripherally inserted central catheter (PICC) line insertion.

Accelerated strategies in the assessment of emergency patients with possible acute coronary syndromes

This thesis synthesises advancements made in the method of assessment of emergency patients with possible acute cardiac disease and has defined new assessment strategies that supports the safe early discharge of patients at low risk for acute coronary syndromes. These important findings have informed clinicians and health services about improvements that can be made at this current time in the process of care of ED patients, and the studies have had local, national and international influence.

Respiratory Exacerbations in Indigenous Children From Two Countries With Non-Cystic Fibrosis Chronic Suppurative Lung Disease/Bronchiectasis

BACKGROUND: Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis. METHODS: Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter. RESULTS: Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators. CONCLUSIONS: AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care.

Prospective external validation of an accelerated (2-h) acute coronary syndrome rule-out process using a contemporary troponin assay

Background: Recently there have been efforts to derive safe, efficient processes to rule out acute coronary syndrome (ACS) in emergency department (ED) chest pain patients. We aimed to prospectively validate an ACS assessment pathway (the 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker (ADAPT) pathway) under pragmatic ED working conditions. Methods: This prospective cohort study included patients with atraumatic chest pain in whom ACS was suspected but who did not have clear evidence of ischaemia on ECG. Thrombolysis in myocardial infarction (TIMI) score and troponin (TnI Ultra) were measured at ED presentation, 2 h later and according to current national recommendations. The primary outcome of interest was the occurrence of major adverse cardiac events (MACE) including prevalent myocardial infarction (MI) at 30 days in the group who had a TIMI score of 0 and had presentation and 2-h TnI assays <99th percentile. Results: Eight hundred and forty patients were studied of whom 177 (21%) had a TIMI score of 0. There were no MI, MACE or revascularization in the per protocol and intention-to-treat 2-h troponin groups (0%, 95% confidence interval (CI) 0% to 4.5% and 0%, 95% CI 0% to 3.8%, respectively). The negative predictive value (NPV) was 100% (95% CI 95.5% to 100%) and 100% (95% CI 96.2% to 100%), respectively. Conclusions: A 2-h accelerated rule-out process for ED chest pain patients using electrocardiography, a TIMI score of 0 and a contemporary sensitive troponin assay accurately identifies a group at very low risk of 30-day MI or MACE.

Clinical pathways for chronic cough in children

Background Chronic cough (a cough lasting longer than four weeks) is a common problem internationally. Chronic cough has associated economic costs and is distressing to the child and to parents; ignoring cough may lead to delayed diagnosis and progression of serious underlying respiratory disease. Clinical guidelines have been shown to lead to efficient and effective patient care and can facilitate clinical decision making. Cough guidelines have been designed to facilitate the management of chronic cough. However, treatment recommendations vary, and specific clinical pathways for the treatment of chronic cough in children are important, as causes of and treatments for cough vary significantly from those in adults. Therefore, systematic evaluation of the use of evidence-based clinical pathways for the management of chronic cough in children would be beneficial for clinical practice and for patient care. Use of a management algorithm can improve clinical outcomes; such management guidelines can be found in the guidelines for cough provided by the American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS). Objectives To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. Search methods The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of re levant articles were searched. The latest search was conducted in January 2014. Selection criteria All randomised controlled trials of parallel-group design comparing use versus non-use of a clinical pathway for treatment of chronic cough in children (< 18 years of age). Data collection and analysis Results of searches were reviewed against predetermined cr iteria for inclusion. Two review authors independently selected studies and performed data extraction in duplicate. Main results One study was included in the review. This multi-centre trial was based in five Australian hospitals and recruited 272 children with chronic cough. Children were randomly assigned to early (two weeks) or delayed (six weeks) referral to respiratory specialists who used a cough management pathway. When an intention-to-treat analysis was performed, clinical failure at six wee ks post randomisation (defined as < 75% improvement in cough score, or total resolution for fewer than three consecutive days) was significantly less in the early pathway arm compared with the control arm (odds ratio (OR) 0.35, 95% confidence interval (CI) 0.21 to 0.58). These results indicate that one additional child will be cured for e very five children treated via th e cough pathway (number needed to treat for an additional beneficial outcome (NNTB) = 5, 95% CI 3 to 9) at six weeks. Cough-specific parent-reported quality of life scores were significantly better in th e early-pathway group; the mean difference (MD) between groups was 0.60 (95% CI 0.19 to 1.01). Duration of cough post randomisation was significantly shorter in the intervention group (early-pathway arm) compared with the control group (delayed-pathway arm) (MD -2.70 weeks, 95% CI -4.26 to -1.14). Authors’ conclusions. Current evidence suggests that using a clinical algorithm for the management of children with ch r onic cough in h ospital outpatient settings is more effective than providing wait-list care. Futher high-quality randomised controlled trials are needed to perform ongoing evaluation of cough management pathways in general practitioner and other primary care settings.

Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features

Objective National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated Methods A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. Results The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079–0.115%) (one of 1027 patients). Conclusions Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome

Does failed chronic wet cough response to antibiotics predict bronchiectasis?

Aim: To determine whether a child with chronic wet cough and poor response to at least 4 weeks of oral antibiotics is more likely to have bronchiectasis. Methods: All chest multi-detector computerised tomography (MDCT) scans at a single paediatric tertiary hospital from April 2010 to August 2012 were reviewed retrospectively so as to identify those ordered by respiratory physicians for assessment of children with a chronic wet cough. Information regarding age, sex, ethnicity, indication for imaging and the response to at least 4 weeks of antibiotics before having the scan were recorded from their charts. The data were analysed using simple and multiple logistic regression. Results: Of the 144 (87 males) eligible children, 106 (65 males, 30 Indigenous) aged 10–199 months had MDCT scan evidence of bronchiectasis. Antibiotic data were available for 129 children. Among the 105 children with persistent cough despite at least 4 weeks of antibiotics, 88 (83.8%) had bronchiectasis, while of the 24 children whose cough resolved after antibiotics, only six (25.0%) received this diagnosis (adjusted OR 20.9; 95% CI 5.36 to 81.8). Being Indigenous was also independently associated with radiographic evidence of bronchiectasis (adjusted OR 5.86; 95% CI 1.20 to 28.5). Conclusions: Further investigations including a MDCT scan should be considered in a child with a chronic wet cough that persists following 4 weeks of oral antibiotics. However, while reducing the likelihood of underlying bronchiectasis, responding well to a single prolonged course of antibiotics does not exclude this diagnosis completely.

A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis following failed epithelial repair. Mesenchymal stromal cells (MSC), a key component of the stem cell niche in bone marrow and possibly other organs including lung, have been shown to enhance epithelial repair and are effective in preclinical models of inflammation-induced pulmonary fibrosis, but may be profibrotic in some circumstances. METHODS: In this single centre, non-randomized, dose escalation phase 1b trial, patients with moderately severe IPF (diffusing capacity for carbon monoxide (DLCO ) ≥ 25% and forced vital capacity (FVC) ≥ 50%) received either 1 × 10(6) (n = 4) or 2 × 10(6) (n = 4) unrelated-donor, placenta-derived MSC/kg via a peripheral vein and were followed for 6 months with lung function (FVC and DLCO ), 6-min walk distance (6MWD) and computed tomography (CT) chest. RESULTS: Eight patients (4 female, aged 63.5 (57-75) years) with median (interquartile range) FVC 60 (52.5-74.5)% and DLCO 34.5 (29.5-40)% predicted were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1% (0-2%)) fall in SaO2 after 15 min, but no changes in haemodynamics. At 6 months FVC, DLCO , 6MWD and CT fibrosis score were unchanged compared with baseline. There was no evidence of worsening fibrosis. CONCLUSIONS: Intravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF.