Non-alcoholic fatty liver disease : can ultrasound assist in early diagnosis of prediabetes and delay progression to type2 diabetes mellitus

Non Alcoholic Fatty Liver Disease (NAFLD) is a condition that is frequently seen but seldom investigated. Until recently, NAFLD was considered benign, self-limiting and unworthy of further investigation. This opinion is based on retrospective studies with relatively small numbers and scant follow-up of histology data. (1) The prevalence for adults, in the USA is, 30%, and NAFLD is recognized as a common and increasing form of liver disease in the paediatric population (1). Australian data, from New South Wales, suggests the prevalence of NAFLD in “healthy” 15 year olds as being 10%.(2) Non-alcoholic fatty liver disease is a condition where fat progressively invades the liver parenchyma. The degree of infiltration ranges from simple steatosis (fat only) to steatohepatitis (fat and inflammation) steatohepatitis plus fibrosis (fat, inflammation and fibrosis) to cirrhosis (replacement of liver texture by scarred, fibrotic and non functioning tissue).Non-alcoholic fatty liver is diagnosed by exclusion rather than inclusion. None of the currently available diagnostic techniques -liver biopsy, liver function tests (LFT) or Imaging; ultrasound, Computerised tomography (CT) or Magnetic Resonance Imaging (MRI) are specific for non-alcoholic fatty liver. An association exists between NAFLD, Non Alcoholic Steatosis Hepatitis (NASH) and irreversible liver damage, cirrhosis and hepatoma. However, a more pervasive aspect of NAFLD is the association with Metabolic Syndrome. This Syndrome is categorised by increased insulin resistance (IR) and NAFLD is thought to be the hepatic representation. Those with NAFLD have an increased risk of death (3) and it is an independent predictor of atherosclerosis and cardiovascular disease (1). Liver biopsy is considered the gold standard for diagnosis, (4), and grading and staging, of non-alcoholic fatty liver disease. Fatty-liver is diagnosed when there is macrovesicular steatosis with displacement of the nucleus to the edge of the cell and at least 5% of the hepatocytes are seen to contain fat (4).Steatosis represents fat accumulation in liver tissue without inflammation. However, it is only called non-alcoholic fatty liver disease when alcohol - >20gms-30gms per day (5), has been excluded from the diet. Both non-alcoholic and alcoholic fatty liver are identical on histology. (4).LFT’s are indicative, not diagnostic. They indicate that a condition may be present but they are unable to diagnosis what the condition is. When a patient presents with raised fasting blood glucose, low HDL (high density lipoprotein), and elevated fasting triacylglycerols they are likely to have NAFLD. (6) Of the imaging techniques MRI is the least variable and the most reproducible. With CT scanning liver fat content can be semi quantitatively estimated. With increasing hepatic steatosis, liver attenuation values decrease by 1.6 Hounsfield units for every milligram of triglyceride deposited per gram of liver tissue (7). Ultrasound permits early detection of fatty liver, often in the preclinical stages before symptoms are present and serum alterations occur. Earlier, accurate reporting of this condition will allow appropriate intervention resulting in better patient health outcomes. References 1. Chalasami N. Does fat alone cause significant liver disease: It remains unclear whether simple steatosis is truly benign. American Gastroenterological Association Perspectives, February/March 2008 www.gastro.org/wmspage.cfm?parm1=5097 Viewed 20th October, 2008 2. Booth, M. George, J.Denney-Wilson, E: The population prevalence of adverse concentrations with adiposity of liver tests among Australian adolescents. Journal of Paediatrics and Child Health.2008 November 3. Catalano, D, Trovato, GM, Martines, GF, Randazzo, M, Tonzuso, A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study .Liver Int.2008; February 1280-9 4. Choudhury, J, Sanysl, A. Clinical aspects of Fatty Liver Disease. Semin in Liver Dis. 2004:24 (4):349-62 5. Dionysus Study Group. Drinking factors as cofactors of risk for alcohol induced liver change. Gut. 1997; 41 845-50 6. Preiss, D, Sattar, N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci.2008; 115 141-50 7. American Gastroenterological Association. Technical review on nonalcoholic fatty liver disease. Gastroenterology.2002; 123: 1705-25

Plasma-enabled carbon nanostructures for early diagnosis of neurodegenerative diseases

Carbon nanostructures (CNs) are amongst the most promising biorecognition nanomaterials due to their unprecedented optical, electrical and structural properties. As such, CNs may be harnessed to tackle the detrimental public health and socio-economic adversities associated with neurodegenerative diseases (NDs). In particular, CNs may be tailored for a specific determination of biomarkers indicative of NDs. However, the realization of such a biosensor represents a significant technological challenge in the uniform fabrication of CNs with outstanding qualities in order to facilitate a highly-sensitive detection of biomarkers suspended in complex biological environments. Notably, the versatility of plasma-based techniques for the synthesis and surface modification of CNs may be embraced to optimize the biorecognition performance and capabilities. This review surveys the recent advances in CN-based biosensors, and highlights the benefits of plasma-processing techniques to enable, enhance, and tailor the performance and optimize the fabrication of CNs, towards the construction of biosensors with unparalleled performance for the early diagnosis of NDs, via a plethora of energy-efficient, environmentally-benign, and inexpensive approaches.

Evidence-based recommendations for the diagnosis of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

• As part of the 3E program, we conducted a systematic literature review and gathered consensus from 23 practising Australian rheumatologists to develop guidelines for early identification of ankylosing spondylitis and specialist referral. • In three rounds of break-out sessions followed by discussion and voting, the specialist panel addressed three questions related to diagnosis of ankylosing spondylitis: In individuals with back pain, what are the early clinical features that suggest ankylosing spondylitis? How useful is imaging in identifying early ankylosing spondylitis? Based on which clinical features should a general practitioner refer a patient to a rheumatologist for further evaluation? • The panel agreed on six recommendations related to the three questions: 1a. Early clinical features to suggest ankylosing spondylitis include inflammatory back pain and age at symptom onset < 45 years. 1b. The absence of symptomatic response to an appropriate course of non-steroidal anti-inflammatory drugs makes the diagnosis of ankylosing spondylitis less likely. 1c. Raised inflammatory markers are supportive, but their absence does not rule out the diagnosis of ankylosing spondylitis. 2a. Despite low sensitivity to detect changes of early ankylosing spondylitis, plain radiographs of the pelvis and spine are appropriate initial imaging techniques. 2b. Magnetic resonance imaging is a useful imaging modality for detecting early changes of ankylosing spondylitis. 3. Individuals with inflammatory back pain should be referred to a rheumatologist for further evaluation. • Effective dissemination and implementation of these recommendations are important to standardise the approach to early diagnosis of ankylosing spondylitis.

Early users of fertility treatment with hormones and IVF : women who live in major cities and have private health insurance

Objective: To identify early users (women aged <34 years) of fertility treatment with hormones and in vitro fertilisation (IVF). Methods: A cross-sectional survey of infertile women from fertility clinics (n=59) and from the community (Australian Longitudinal Study on Women's Health participants) who had (n=121) or had not (n=110) used hormones/IVF as treatment for infertility. Associations between socio-demographic, reproductive and lifestyle factors, medical conditions and recurrent symptoms and using treatment (or not) were analysed using multivariable logistic regression. Results: Among infertile women who had used treatment (community vs clinic), women from clinics had lower odds of living outside major cities, using hormones only, i.e., not IVF, or recurrent headaches/migraines, severe tiredness, or stiff/painful joints; and higher odds of recent diagnoses of urinary tract infection or anxiety disorder. Compared to infertile women who had not used treatment, women from clinics had lower odds of living outside major cities, recurrent allergies or severe tiredness; and higher odds of having private health insurance for hospital or ancillary services, recent diagnosis of polycystic ovary syndrome or recurrent constipation. Conclusions: Compared to infertile women in the community, living in major cities and having private health insurance are associated with early use of treatment for infertility at specialist clinics by women aged <34 years. Implications: These results provided evidence of inequity of services for infertile women.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children : a study protocol for a randomised controlled trial

Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children.

The knowledge translation pathway for timely diagnosis of dementia

There has been significant debate about the value of screening for dementia, and the need for early diagnosis. Options include Gene testing, early risk assessment, screening, case finding and review when a patient or carer identify that they have symptoms. This paper is not focused on these early approaches to identifying people with dementia. It is focused on the period when a patient or a carer has recognised that there are some memory problems and they are seeking assistance with a diagnosis or explanation in relation to memory loss.

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.

Condition monitoring and fault diagnosis of diesel engines using instantaneous angular speed analysis

Continuous monitoring of diesel engine performance is critical for early detection of fault developments in an engine before they materialize into a functional failure. Instantaneous crank angular speed (IAS) analysis is one of a few nonintrusive condition monitoring techniques that can be utilized for such a task. Furthermore, the technique is more suitable for mass industry deployments than other non-intrusive methods such as vibration and acoustic emission techniques due to the low instrumentation cost, smaller data size and robust signal clarity since IAS is not affected by the engine operation noise and noise from the surrounding environment. A combination of IAS and order analysis was employed in this experimental study and the major order component of the IAS spectrum was used for engine loading estimation and fault diagnosis of a four-stroke four-cylinder diesel engine. It was shown that IAS analysis can provide useful information about engine speed variation caused by changing piston momentum and crankshaft acceleration during the engine combustion process. It was also found that the major order component of the IAS spectra directly associated with the engine firing frequency (at twice the mean shaft rotating speed) can be utilized to estimate engine loading condition regardless of whether the engine is operating at healthy condition or with faults. The amplitude of this order component follows a distinctive exponential curve as the loading condition changes. A mathematical relationship was then established in the paper to estimate the engine power output based on the amplitude of this order component of the IAS spectrum. It was further illustrated that IAS technique can be employed for the detection of a simulated exhaust valve fault in this study.

Automated diagnosis of Age-related Macular Degeneration using greyscale features from digital fundus images

Age-related Macular Degeneration (AMD) is one of the major causes of vision loss and blindness in ageing population. Currently, there is no cure for AMD, however early detection and subsequent treatment may prevent the severe vision loss or slow the progression of the disease. AMD can be classified into two types: dry and wet AMDs. The people with macular degeneration are mostly affected by dry AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These lesions are identified by manual inspection of fundus images by the ophthalmologists. It is a time consuming, tiresome process, and hence an automated diagnosis of AMD screening tool can aid clinicians in their diagnosis significantly. This study proposes an automated dry AMD detection system using various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS) bispectra features, Fractional Dimension (FD), and Gabor wavelet features extracted from greyscale fundus images. The features are ranked using t-test, Kullback–Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance (CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking methods in order to select optimum features and classified into normal and AMD classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers. The performance of the proposed system is evaluated using private (Kasturba Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) datasets. The proposed system yielded the highest average classification accuracies of 90.19%, 95.07% and 95% with 42, 54 and 38 optimal ranked features using SVM classifier for private, ARIA and STARE datasets respectively. This automated AMD detection system can be used for mass fundus image screening and aid clinicians by making better use of their expertise on selected images that require further examination.

Teaching children who have a diagnosis of Autism Spectrum Disorder

Best practice dictates that the Autism Spectrum Disorder (ASD) diagnostic process is informed by experienced professionals from at least two disciplines, for example psychology or speech pathology, with the diagnosis ultimately provided by a specialist medical practitioner e.g. child psychiatrist, neurologist or paediatrician. Irrespective of a child’s age, diagnosis relies upon information about their early development. Current information and observations on a child’s behaviour, communication and socialisation are considered by the specialist medical practitioner against the signs and symptoms detailed in one of several diagnostic systems. Two recently used classification systems in Australia have been the fourth edition of the Diagnostic Statistical Manual of Mental Disorders (DSM-IV) published by the American Psychiatric Association (1994) and the tenth edition of the International Classification of Disease (ICD-10), published by the World Health Organisation (2003).

Current trends in the etiology and diagnosis of HPV-related head and neck cancers

Human papilloma virus (HPV) infection is a major risk factor for a distinct subset of head and neck squamous cell carcinoma (HNSCC). The current review summarizes the epidemiology of HNSCC and the disease burden, the infectious cycle of HPV, the roles of viral oncoproteins, E6 and E7, and the downstream cellular events that lead to malignant transformation. Current techniques for the clinical diagnosis of HPV-associated HNSCC will also be discussed, that is, the detection of HPV DNA, RNA, and the HPV surrogate marker, p16 in tumor tissues, as well as HPV-specific antibodies in serum. Such methods do not allow for the early detection of HPV-associated HNSCC and most cases are at an advanced stage upon diagnosis. Novel noninvasive approaches using oral fluid, a clinically relevant biological fluid, allow for the detection of HPV and cellular alterations in infected cells, which may aid in the early detection and HPV-typing of HNSCC tumors. Noninvasive diagnostic methods will enable early detection and intervention, leading to a significant reduction in mortality and morbidity associated with HNSCC.