Comparison of high sensitivity troponin T and I assays in the diagnosis of non-ST elevation acute myocardial infarction in emergency patients with chest pain

Objectives: Concentrations of troponin measured with high sensitivity troponin assays are raised in a number of emergency department (ED) patients; however many are not diagnosed with acute myocardial infarction (AMI). Clinical comparisons between the early use (2 h after presentation) of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) assays for the diagnosis of AMI have not been reported. Design and methods: Early (0 h and 2 h) hs-cTnT and hs-cTnI assay results in 1571 ED patients with potential acute coronary syndrome (ACS) without ST elevation on electrocardiograph (ECG) were evaluated. The primary outcome was diagnosis of index MI adjudicated by cardiologists using the local cTnI assay results taken ≥6 h after presentation, ECGs and clinical information. Stored samples were later analysed with hs-cTnT and hs-cTnI assays. Results: The ROC analysis for AMI (204 patients; 13.0%) for hs-cTnT and hs-cTnI after 2 h was 0.95 (95% CI: 0.94–0.97) and 0.98 (95% CI: 0.97–0.99) respectively. The sensitivity, specificity, PLR, and NLR of hs-cTnT and hs-cTnI for AMI after 2 h were 94.1% (95% CI: 90.0–96.6) and 95.6% (95% CI: 91.8–97.7), 79.0% (95% CI: 76.8–81.1) and 92.5% (95% CI: 90.9–93.7), 4.48 (95% CI: 4.02–5.00) and 12.86 (95% CI: 10.51–15.31), and 0.07 (95% CI: 0.04–0.13) and 0.05 (95% CI:0.03–0.09) respectively. Conclusions: Exclusion of AMI 2 h after presentation in emergency patients with possible ACS can be achieved using hs-cTnT or hs-cTnI assays. Significant differences in specificity of these assays are relevant and if using the hs-cTnT assay, further clinical assessment in a larger proportion of patients would be required.

miR-126 in human cancers : clinical roles and current perspectives

miR-126 has been implicated in the processes of inflammation and angiogenesis. Through these processes, miR-126 is implicated in cancer biology, but its role there has not been well reviewed. The aim of this review is to examine the molecular mechanisms and clinicopathological significance of miR-126 in human cancers. miR-126 was shown to have roles in cancers of the gastrointestinal tract, genital tracts, breast, thyroid, lung and some other cancers. Its expression was suppressed in most of the cancers studied. The molecular mechanisms that are known to cause aberrant expression of miR-126 include alterations in gene sequence, epigenetic modification and alteration of dicer abundance. miR-126 can inhibit progression of some cancers via negative control of proliferation, migration, invasion, and cell survival. In some instances, however, miR-126 supports cancer progression via promotion of blood vessel formation. Downregulation of miR-126 induces cancer cell proliferation, migration, and invasion via targeting specific oncogenes. Also, reduced levels of miR-126 are a significant predictor of poor survival of patients in many cancers. In addition, miR-126 can alter a multitude of cellular mechanisms in cancer pathogenesis via suppressing gene translation of numerous validated targets such as PI3K, KRAS, EGFL7, CRK, ADAM9, HOXA9, IRS-1, SOX-2, SLC7A5 and VEGF. To conclude, miR-126 is commonly down-regulated in cancer, most likely due to its ability to inhibit cancer cell growth, adhesion, migration, and invasion through suppressing a range of important gene targets. Understanding these mechanisms by which miR-126 is involved with cancer pathogenesis will be useful in the development of therapeutic targets for the management of patients with cancer.

Carcinoma ex pleomorphic adenoma : a comprehensive review of clinical, pathological and molecular data

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. This study intends to review the literature and highlight the current clinical and molecular perspectives about this entity. The most common clinical presentation of CA ex PA is of a firm mass in the parotid gland. The proportion of adenoma and carcinoma components determines the macroscopic features of this neoplasm. The entity is difficult to diagnose pre-operatively. Pathologic assessment is the gold standard for making the diagnosis. Treatment for Ca ex PA often involves an ablative surgical procedure which may be followed by radiotherapy. Overall, patients with Ca ex PA have a poor prognosis. Accurate diagnosis and aggressive surgical management of patients presenting with Ca ex PA can increase their survival rates. Molecular studies have revealed that the development of Ca ex PA follows a multi-step model of carcinogenesis, with the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and finally 17p. There are specific candidate genes in these regions that are associated with particular stages in the progression of Ca ex PA. In addition, many genes which regulate tumour suppression, cell cycle control, growth factors and cell-cell adhesion play a role in the development and progression of Ca ex PA. It is hopeful that these molecular data can give clues for the diagnosis and management of the disease.

Clinical utility of exhaled nitric oxide

Lower airway inflammation is generally classified as eosinophilic or neutrophilic. In conditions where eosinophilic inflammation predominates such as asthma in children, corticosteroids are usually beneficial. Traditionally, lower airway eosinophilia is measured using cellular count (through bronchoalveolar lavage or induced sputum). Both methods have limited applicability in children. When instruments to measure fractional exhaled nitric oxide (FeNO) became available, it presented an attractive option as it provided a non-invasive method of measuring eosinophilic inflammation suitable for children and adult. Not surprisingly, proposals have been made that FeNO measurement can be clinically used in many scenarios including monitoring the response to anti-inflammatory medications, to verify the adherence to treatment, and to predict upcoming asthma exacerbations. This thesis addresses the utility of FeNO levels in various scenarios, specifically in relation to asthma control and cough, a contentious aspect of the diagnosis of asthma. The thesis consists of a series of systematic reviews (related to the main question) and original studies in children. The over-arching aim of the thesis is to determine if FeNO is a clinically useful tool in the management of asthma and common asthma symptoms. The specific aims of the thesis were, to: 1. Determine if children with asthma have more severe acute respiratory symptoms at presentation with an asthma exacerbation and at days 7, 10 and 14 using validated scales. We also examined if children with asthma were more likely to have a persistent cough on day 14 than children with protracted bronchitis and/or controls. 2. Evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. 3. Evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. 4. Determine if adjustment of asthma medications based on FeNO levels (compared to management based on clinical symptoms) reduces severe exacerbations in children with asthma. 5. Examine the relationship between FeNO and exercise induced broncho-constriction and cough in children The aims above are addressed in respective chapters and all but one has been published/submitted. A synopsis of the findings are: In study-1 (Aim 1), we found that children with protracted bronchitis had the most severe acute respiratory infection symptoms and higher percentage of respiratory morbidity at day 14 in comparison to children with asthma and healthy controls. The systematic review of study-2 (Aim 2) included 246 randomised adult participants (no children) with 221 completing the trials. In the meta-analysis, a significant reduction in number of participants who had one or more asthma exacerbations occurred when treatment was based on sputum eosinophils in comparison to clinical symptoms. In the systematic review of study-3 (Aim 3), we found no significant difference between the intervention group (treatment adjusted based on FeNO) and control group (treatment adjusted based on clinical symptoms) for the primary outcome of asthma exacerbations or for the other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose ICS per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms. In contrast, in the paediatric studies, there was a significant increase in ICS dose in the FeNO strategy arm. Thus, controversy remains of the benefit or otherwise of utilising exhaled nitric oxide (FeNO) in routine clinical practice. FeNO levels are dependent on atopy and none of the 7 published trials have considered atopic status in FeNO levels when medications were adjusted. In study-4 (Aim 4), 64 children with asthma were recruited. Their asthma medications were adjusted according to either FeNO levels or usual clinical care utilising a management hierarchy taking into account atopy. It was concluded that tailoring of asthma medications in accordance to FeNO levels (compared to usual management), taking into account atopy status, reduced the number of children with severe exacerbations. However, a FeNO-based strategy resulted in higher daily ICS doses and had no benefit on asthma control. In study-5 (Aim 5), 33 children with cough and 17 controls were recruited. They were randomised to undertake an exercise challenge on day 1, or dry powder mannitol challenge on day 1 (with alternative challenge being done on day 2). In addition, a 24 hour cough meter, skin prick test, capsaicin cough sensitivity test and cough diary were undertaken. The change in cough frequency post exercise was significantly increased in the children with cough. FeNO decreases post exercise regardless of whether EIB is present or not. Limitations in the studies were addressed in the respective chapters. In summary, the studies from this thesis have provided new information on: • The severity of respiratory symptoms was increased in the early phase of the asthma exacerbation but not in the later recovery phase when compared with controls. • The utility of FeNO in the management of children with asthma. • The relationship of FeNO, cough and EIB in children. • Systematic reviews on the efficacy of tailoring asthma interventions based on eosinophilic inflammatory markers (sputum analysis and FeNO) in comparison to clinical symptoms.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Prevalence, predictors, and correlates of supportive care needs among women 3–5 years after a diagnosis of endometrial cancer

Purpose The purpose of this study is to examine the prevalence, sociodemographic and clinical predictors, and physical and psychosocial correlates of unmet needs among women 3–5 years following treatment for endometrial cancer. Methods Women with endometrial cancer completed a survey around the time of diagnosis and again 3–5 years later. The follow-up survey asked women about their physical and psychosocial functioning and supportive care needs (CaSUN). Multivariable-adjusted logistic regression identified the predictors and correlates of women’s unmet needs 3–5 years after diagnosis. Results Of the 629 women who completed the cancer survivors’ unmet needs measure (CaSUN), 24 % (n = 153) women reported one or more unmet supportive care needs in the last month. Unmet needs at 3–5 years post-diagnosis were predicted by younger age (OR = 4.47; 95 % CI: 2.09–9.56) and advanced disease stage at diagnosis (OR = 2.47; 95 % CI: 1.38–4.45) and correlated with greater cancer symptoms (OR = 1.78; 95 % CI: 1.05–3.02), lower limb swelling (OR = 2.50; 95 % CI: 1.51–4.15), symptoms of anxiety (OR = 2.21; 95 % CI: 1.31–3.72), and less availability of social support (OR = 3.42; 95 % CI: 1.92–6.11). Women with a history of comorbidities (OR = 0.47; 95 % CI: 0.27–0.82) and those living in a rural area at the time of diagnosis (OR = 0.56; 95 % CI: 0.34–0.92) were less likely to report unmet needs. Conclusions Sociodemographic, health, and psychosocial factors seem important for identifying women who will or will not have unmet needs several years following endometrial cancer. Longitudinal assessments of people’s needs over the course of their cancer trajectory may be an effective way to identify areas that should receive further attention by health providers.

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.

Wheeze, asthma diagnosis and medication use : a national adult survey in a developing country

Background As relatively little is known about adult wheeze and asthma in developing countries, this study aimed to determine the predictors of wheeze, asthma diagnosis, and current treatment in a national survey of South African adults. Methods A stratified national probability sample of households was drawn and all adults (>14 years) in the selected households were interviewed. Outcomes of interest were recent wheeze, asthma diagnosis, and current use of asthma medication. Predictors of interest were sex, age, household asset index, education, racial group, urban residence, medical insurance, domestic exposure to smoky fuels, occupational exposure, smoking, body mass index, and past tuberculosis. Results A total of 5671 men and 8155 women were studied. Although recent wheeze was reported by 14.4% of men and 17.6% of women and asthma diagnosis by 3.7% of men and 3.8% of women, women were less likely than men to be on current treatment (OR 0.6; 95% confidence interval (CI) 0.5 to 0.8). A history of tuberculosis was an independent predictor of both recent wheeze (OR 3.4; 95% CI 2.5 to 4.7) and asthma diagnosis (OR 2.2; 95% CI 1.5 to 3.2), as was occupational exposure (wheeze: OR 1.8; 95% CI 1.5 to 2.0; asthma diagnosis: OR 1.9; 95% CI 1.4 to 2.4). Smoking was associated with wheeze but not asthma diagnosis. Obesity showed an association with wheeze only in younger women. Both wheeze and asthma diagnosis were more prevalent in those with less education but had no association with the asset index. Independently, having medical insurance was associated with a higher prevalence of diagnosis. Conclusions Some of the findings may be to due to reporting bias and heterogeneity of the categories wheeze and asthma diagnosis, which may overlap with post tuberculous airways obstruction and chronic obstructive pulmonary disease due to smoking and occupational exposures. The results underline the importance of controlling tuberculosis and occupational exposures as well as smoking in reducing chronic respiratory morbidity. Validation of the asthma questionnaire in this setting and research into the pathophysiology of post tuberculous airways obstruction are also needed.

The clinical utility of the Cornell Scale for Depression in Dementia as a routine assessment in nursing homes

Objective To examine the clinical utility of the Cornell Scale for Depression in Dementia (CSDD) in nursing homes. Setting 14 nursing homes in Sydney and Brisbane, Australia. Participants 92 residents with a mean age of 85 years. Measurements Consenting residents were assessed by care staff for depression using the CSDD as part of their routine assessment. Specialist clinicians conducted assessment of depression using the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders for residents without dementia or the Provisional Diagnostic Criteria for Depression in Alzheimer Disease for residents with dementia to establish expert clinical diagnoses of depression. The diagnostic performance of the staff completed CSDD was analyzed against expert diagnosis using receiver operating characteristic (ROC) curves. Results The CSDD showed low diagnostic accuracy, with areas under the ROC curve being 0.69, 0.68 and 0.70 for the total sample, residents with dementia and residents without dementia, respectively. At the standard CSDD cutoff score, the sensitivity and specificity were 71% and 59% for the total sample, 69% and 57% for residents with dementia, and 75% and 61% for residents without dementia. The Youden index (for optimizing cut-points) suggested different depression cutoff scores for residents with and without dementia. Conclusion When administered by nursing home staff the clinical utility of the CSDD is highly questionable in identifying depression. The complexity of the scale, the time required for collecting relevant information, and staff skills and knowledge of assessing depression in older people must be considered when using the CSDD in nursing homes.

The effect of the ecstasy 'come-down' on the diagnosis of ecstasy dependence

Background: The existence of an ecstasy dependence syndrome is controversial. We examined whether the acute after-effects of ecstasy use (i.e., the “come-down”) falsely lead to the identification of ecstasy withdrawal and the subsequent diagnosis of ecstasy dependence. Methods: The Structured Clinical Interview for DSM-IV-TR Disorders: Research Version (SCID-RV) was administered to 214 Australian ecstasy users. Ecstasy withdrawal was operationalized in three contrasting ways: (i) as per DSM-IV criteria; (ii) as the expected after effects of ecstasy (a regular come-down); or (iii) as a substantially greater or longer come-down than on first use (intense come-down). These definitions were validated against frequency of ecstasy use, readiness to change and ability to resist the urge to use ecstasy. Confirmatory factor analyses were used to see how they aligned with the overall dependence syndrome. Results: Come-down symptoms increased the prevalence of withdrawal from 1% (DSM-IV criterion) to 11% (intense come-downs) and 75% (regular come-downs). Past year ecstasy dependence remained at 31% when including the DSM-IV withdrawal criteria and was 32% with intense come-downs, but increased to 45% with regular come-downs. Intense come-downs were associated with lower ability to resist ecstasy use and loaded positively on the dependence syndrome. Regular come-downs did not load positively on the ecstasy dependence syndrome and were not related to other indices of dependence. Conclusion: The acute after-effects of ecstasy should be excluded when assessing ecstasy withdrawal as they can lead to a false diagnosis of ecstasy dependence. Worsening of the ecstasy come-down may be a marker for dependence.

Latent class analysis reveals distinct subgroups of patients based on symptom occurrence and demographic and clinical characteristics

Context Cancer patients experience a broad range of physical and psychological symptoms as a result of their disease and its treatment. On average, these patients report ten unrelieved and co-occurring symptoms. Objectives To determine if subgroups of oncology outpatients receiving active treatment (n=582) could be identified based on their distinct experience with thirteen commonly occurring symptoms; to determine whether these subgroups differed on select demographic, and clinical characteristics; and to determine if these subgroups differed on quality of life (QOL) outcomes. Methods Demographic, clinical, and symptom data from one Australian and two U.S. studies were combined. Latent class analysis (LCA) was used to identify patient subgroups with distinct symptom experiences based on self-report data on symptom occurrence using the Memorial Symptom Assessment Scale (MSAS). Results Four distinct latent classes were identified (i.e., All Low (28.0%), Moderate Physical and Lower Psych (26.3%), Moderate Physical and Higher Psych (25.4%), All High (20.3%)). Age, gender, education, cancer diagnosis, and presence of metastatic disease differentiated among the latent classes. Patients in the All High class had the worst QOL scores. Conclusion Findings from this study confirm the large amount of interindividual variability in the symptom experience of oncology patients. The identification of demographic and clinical characteristics that place patients are risk for a higher symptom burden can be used to guide more aggressive and individualized symptom management interventions.

Current practice in nutrition diagnosis and intervention for the management of Parkinson's disease in Australia and Canada

Aim To document current practice by dietitians in Australia and Canada in the nutrition management of Parkinson's disease. This will help identify priority areas for review and development of practice guidelines and direct future research. Methods Current practice in the phases of the Nutrition Care Plan was captured using an online survey distributed to Dietitians Association of Australia members and Practice-Based Evidence in Nutrition subscribers through their email newsletters. The results of the diagnosis, intervention and monitoring phases are presented here. Results Eighty-four dietitians responded. There was consistency in practice for nutrition issues that are encountered in other populations, such as malnutrition and constipation. There was more variation in practice in the nutrition issues that are more specific to Parkinson's disease, such as nutrition and meal interactions with medication. A lack of awareness of emerging treatments, such as deep brain stimulation surgery, appears to exist in the responding dietitians. Conclusions The variation in practice that was present for the nutrition issues specific to Parkinson's disease may reflect the lack of quality evidence and subsequently evidence-based guidelines in these areas. Work to provide background information about treatment options and to translate current evidence for the nutrition issues that are specific to Parkinson's disease into practice recommendations should be completed.