Diagnosis of autistic spectrum disorders in Queensland: Variations in practice

Objective: For both paediatricians and child psychiatrists, referrals to assess possible autistic spectrum disorders (ASD) are increasing. This study examines current practices of medical specialists in the assessment of these disorders. Methods: An anonymous, self-report questionnaire was sent to all Queensland paediatricians and child psychiatrists. The survey elicited frequencies of consultation for ASD, diagnostic method, advice provided and perceived adequacy of training for this work. Results: Responses were received from 79 (85%) eligible paediatricians and 26 (58%) eligible child psychiatrists. For one-third of all clinicians, new consultations for possible ASD occurred as often as 2-3 times per week. Most specialists approached the clinical diagnosis of ASD by considering history from different sources and professional assessments. Paediatricians (86%) were more likely than child psychiatrists (62%) to request genetic studies for children with severe autism (P = 0.01). Both general paediatricians and developmental paediatricians perceived level of training for possible ASD consultations was significantly worse than child psychiatrists (P < 0.001 and P = 0.02, respectively), but no difference was found between paediatric groups (P = 0.27). Perceived adequacy of specialist training was not associated with length of experience in clinical practice. Conclusion: Medical practice in Queensland around diagnosis of ASD is characterized by considerable variability. There is still a long way to go if we are to achieve consistency around medical issues of organic diagnosis and practices impacting on health as well as consideration of differential developmental diagnoses. The finding that recently trained paediatricians felt just as unprepared for this work as their older colleagues suggests that the graduate training response to this 'new morbidity' has not been adequate.

A study of potential serum markers for a diagnosis of gram-positive and gram-negative bacterial sepsis

Sepsis continues to be a major cause of morbidity and mortality as it can readily lead tosevere sepsis, septic shock, multiple organ failure and death. The onset can be rapid and difficult to define clinically. Despite the numerous candidate markers proposed in the literature, to date a serum marker for sepsis has not been found. The aim of this study was to assay the serum of clinically diagnosed patients with eithera Gram-negative or Gram- positive bacterial sepsis for elevated levels of nine potentialmarkers of sepsis, using commercially produced enzyme linked immunosorbent assays(ELISA). The purpose was to find a test marker for sepsis that would be helpful toclinicians in cases of uncertain sepsis and consequently expose false positive BC'scaused by skin or environmental contaminants. Nine test markers were assayed including IL-6, IL-I 0, ILI2, TNF-α, lipopolysaccharide binding protein, procalcitonin, sE-selectin, sICAM -1 and a potential differential marker for Gram-positive sepsis- anti-lipid S antibody. A total of 445 patients were enrolled into this study from the Queen Elizabeth Hospital and Selly Oak Hospital (Birmingham). The results showed that all the markers were elevated in patients with sepsis and that patients with a Gram-negative sepsis consistently produced higher median/range serum levels than those with a Gram-positive sepsis. No single marker was able to identify all the septic patients. Combining two markers caused the sensitivities and specificities for a diagnosis of sepsis to increase to within a 90% to 100% range. By a process of elimination the markers that survived into the last phase were IL-6 with sICAM -1, and anti-lipid S IgG assays Defining cut-off levels for a diagnosis of sepsis became problematic and a semi-blind trial was devised to test the markers in the absence of both clinical details and positive blood cultures. Patients with pyrexia of unknown origin and negative BC were included in this phase (4). The results showed that IL-6 with sICAM-l are authentic markers of sepsis. There was 82% agreement between the test marker diagnosis and the clinical diagnosis for sepsis in patients with a Gram-positive BC and 78% agreement in cases of Gram-negative Be. In the PUO group the test markers identified 12 cases of sepsis and the clinical diagnosis 15. The markers were shown to differentiate between early sepsis and sepsis, inflammatory responses and infection. Anti-lipid S with IL-6 proved be a sensitive marker for Gram-positive infections/sepsis.

Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

Eye movement problems and differential diagnosis of the parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes, viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) can be difficult. Eye movement problems, however, are a chronic complication of many of these disorders and may be a useful aid to diagnosis. Hence, the presence in PSP of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm, and apraxia of eyelid opening and closing is useful in separating PD from PSP. Moreover, atypical features of PSP include slowing of upward saccades, moderate slowing of downward saccades, the presence of a full range of voluntary vertical eye movements, a curved trajectory of oblique saccades, and absence of square-wave jerks. Downgaze palsy is probably the most useful diagnostic clinical symptom of PSP. By contrast, DLB patients are specifically impaired in both reflexive and saccadic execution and in the performance of more complex saccadic eye movement tasks. Problems in convergence in DLB are also followed by akinesia and rigidity. Abnormal ocular fixation may occur in a significant proportion of MSA patients along with excessive square-wave jerks, a mild supranuclear gaze palsy, a gaze-evoked nystagmus, a positioning down-beat nystagmus, mild-moderate saccadic hypometria, impaired smooth pursuit movements, and reduced vestibulo-ocular reflex (VOR) suppression. There may be considerable overlap between the eye movement problems characteristic of the various parkinsonian disorders, but taken together with other signs and symptoms, can be a useful aid in differential diagnosis, especially in the separation of PD and PSP.

Impact of suspected food allergy on emotional distress and family life of parents prior to allergy diagnosis

Background: Food allergy is associated with psychological distress in both child and parent. It is unknown whether parental distress is present prior to clinical diagnosis or whether experiences at clinic can reduce any distress present. This study aimed to assess anxiety and depression in parents and the impact of suspected food allergy on the lives of families before and after a visit to an allergy clinic. Methods: One hundred and twenty-four parents visiting an allergy clinic for the first time to have their child assessed for food allergy completed a study-specific questionnaire and the Hospital Anxiety and Depression Scale; 50 parents completed these 4-6 wk later in their own home. Results: Most parents (86.4%) reported suspected food allergy had an impact on their family life prior to clinic attendance; 76% had made changes to their child's diet. 32.5% of parents had mild-to-severe anxiety before their clinic visit; 17.5% had mild-to-moderate depression. Post-clinic, 40% had mild-to-severe anxiety; 13.1% had mild-to-moderate depression. There were no significant differences in anxiety (p = 0.34) or depression scores (p = 0.09) before and after the clinic visit. Conclusions: Anxiety and depression is present in a small proportion of parents prior to diagnosis of food allergy in their child and this does not reduce in the short term after the clinic visit. Identification of parents at risk of suffering from distress is needed and ways in which we communicate allergy information before and at clinic should be investigated to see if we can reduce distress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ambulatory electroencephalogram in children:a prospective clinical audit of 100 cases

Ambulatory electroencephalogram has been used for differentiating epileptic from nonepileptic events, recording seizure frequency and classification of seizure type. We studied 100 consecutive children prospectively aged 11 days to 16 years that were referred for an ambulatory electroencephalogram to a regional children's hospital. Ambulatory electroencephalogram was clinically useful in contributing to a clinical diagnosis in 71% of children who were referred with a range of clinical questions. A diagnosis of epileptic disorder was confirmed by obtaining an ictal record in 26% and this included 11 children that had previously normal awake and or sleep electroencephalogram. We recommend making a telephone check of the current target event frequency and prioritising those with typical events on most days in order to improve the frequency of recording a typical attack.

Signposting for diagnosis of Autism Spectrum Disorder using the Diagnostic Interview for Social and Communication Disorders (DISCO)

Recent research has investigated the capability of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) descriptions to identify individuals who should receive a diagnosis of Autism Spectrum Disorder (ASD) using standardised diagnostic instruments. Building on previous research investigating behaviours essential for the diagnosis of DSM-5 ASD, the current study investigated the sensitivity and specificity of a set of 14 items derived from the Diagnostic Interview for Social and Communication Disorders (DISCO Signposting set) that have potential for signposting the diagnosis of autism according to both the new DSM-5 criteria for ASD and ICD-10 criteria for Childhood Autism. An algorithm threshold for the Signposting set was calculated in Sample 1 (n = 67), tested in an independent validation sample (Sample 2; n = 78), and applied across age and ability sub-groups in Sample 3 (n = 190). The algorithm had excellent predictive validity according to best estimate clinical diagnosis (Samples 1 and 2) and excellent agreement with established algorithms for both DSM-5 and ICD-10 (all samples). The signposting set has potential to inform our understanding of the profile of ASD in relation to other neurodevelopmental disorders and to form the basis of a Signposting Interview for use in clinical practice.

The tuberous sclerosis 2000 study:presentation initial assessments and implications for diagnosis and management

Aims: The Tuberous Sclerosis 2000 Study is the first comprehensive longitudinal study of tuberous sclerosis (TS) and aims to identify factors that determine prognosis. Mode of presentation and findings at initial assessments are reported here. Methods: Children aged 0-16 years newly diagnosed with TS in the UK were evaluated. Results: 125 children with TS were studied. 114 (91%) met clinical criteria for a definite diagnosis and the remaining 11 (9%) had pathogenic TSC1 or TSC2 mutations. In families with a definite clinical diagnosis, the detection rate for pathogenic mutations was 89%. 21 cases (17%) were identified prenatally, usually with abnormalities found at routine antenatal ultrasound examination. 30 cases (24%) presented before developing seizures and in 10 of these without a definite diagnosis at onset of seizures, genetic testing could have confirmed TS. 77 cases (62%) presented with seizures. Median age at recruitment assessment was 2.7 years (range:4 weeks-18 years). Dermatological features of TS were present in 81%. The detection rate of TS abnormalities was 20/107 (19%) for renal ultrasound including three cases with polycystic kidney disease, 51/88 (58%) for echocardiography, 29/35 (83%) for cranial CT and 95/104 (91%) for cranial MRI. 91% of cases had epilepsy and 65% had intellectual disability (IQ<70). Conclusions: Genetic testing can be valuable in confirming the diagnosis. Increasing numbers of cases present prenatally or in early infancy, before onset of seizures, raising important questions about whether these children should have EEG monitoring and concerning the criteria for starting anticonvulsant therapy.

Structural determination and gynecological tumor diagnosis using antibody chip captured proteins

Purpose: To identify markers for gynecological tumor diagnosis using antibody chip capture. Methods: Marker proteins, including cancer antigen 153 (CA153), CA125, and carcinoembryonic antigen (CEA), were analyzed using antibody chip capture of serum samples. Fifteen agglutinin types that specifically recognized five common glycans (fucose, sialic acid, mannose, N - acetylgalactosamine, and N-acetylglucosamine) were used to detect marker protein glycan levels. The levels of CA153, CA125, and CEA from 49 healthy control samples, 31 breast cancer samples, 24 cervical cancer samples, and 19 ovarian cancer samples were used to measure the glycan levels of these marker proteins. Results: In breast cancer samples, CA153 and CA125 were down-regulated (p < 0.01), while differences in ovarian cancer samples were not statistically significant (p > 0.01). The total accuracy was 85.1 %, with 96.8 % accuracy for breast cancer, 75 % in cervical cancer, and 78.9 % in ovarian cancer. Cross-validation analyses showed that breast cancer had 93.5 % accuracy, cervical cancer was 66.7 %, and ovarian cancer was 68.4 %, leading to 78.4 % total accuracy (58/74). Conclusions: The results indicate that better clinical diagnosis of gynecological tumors can be obtained by monitoring changes in glycan levels of serum proteins and types of proteoglycan changes.

Bayesian latent trait modeling of migraine symptom data

Definition of disease phenotype is a necessary preliminary to research into genetic causes of a complex disease. Clinical diagnosis of migraine is currently based on diagnostic criteria developed by the International Headache Society. Previously, we examined the natural clustering of these diagnostic symptoms using latent class analysis (LCA) and found that a four-class model was preferred. However, the classes can be ordered such that all symptoms progressively intensify, suggesting that a single continuous variable representing disease severity may provide a better model. Here, we compare two models: item response theory and LCA, each constructed within a Bayesian context. A deviance information criterion is used to assess model fit. We phenotyped our population sample using these models, estimated heritability and conducted genome-wide linkage analysis using Merlin-qtl. LCA with four classes was again preferred. After transformation, phenotypic trait values derived from both models are highly correlated (correlation = 0.99) and consequently results from subsequent genetic analyses were similar. Heritability was estimated at 0.37, while multipoint linkage analysis produced genome-wide significant linkage to chromosome 7q31-q33 and suggestive linkage to chromosomes 1 and 2. We argue that such continuous measures are a powerful tool for identifying genes contributing to migraine susceptibility.

The ability of economic thinking : the “nature” versus “nurture” debate

In their studies, Eley and Meyer (2004) and Meyer and Cleary (1998) found that there are sources of variation in the affective and process dimensions of learning in mathematics and clinical diagnosis specific to each of these disciplines. Meyer and Shanahan (2002) argue that: General purpose models of student learning that are transportable across different discipline contexts cannot, by definition, be sensitive to sources of variation that may be subject-specific (2002. p. 204). In other words, to explain the differences in learning approaches and outcomes in a particular discipline, there are discipline-specific factors, which cannot be uncovered in general educational research. Meyer and Shanahan (2002) argue for a need to "seek additional sources of variation that are perhaps conceptually unique ... within the discourse of particular disciplines" (p. 204). In this paper, the development of an economics-specific construct (called economic thinking ability) is reported. The construct aims to measure discipline-sited ability of students that has important influence on learning in economics. Using this construct, economic thinking abilities of introductory and intermediate level economics students were measured prior to the commencement, and at the end, of their study over one semester. This enabled factors associated with students' pre-course economic thinking ability and their development in economic thinking ability to be investigated. The empirical findings will address the 'nature' versus 'nurture' debate in economics education (Frank, et aI., 1993; Frey et al., 1993; Haucap and Tobias 2003). The implications for future research in economics education will also be discussed.

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice

Background Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors. Objectives To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care. Methods This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. Results Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥50years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. Conclusions More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.

Plasma metabolomics reveals biomarkers of the atherosclerosis

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in industrialized societies. The lack of metabolite biomarkers has impeded the clinical diagnosis of atherosclerosis so far. In this study, stable atherosclerosis patients (n=16) and age- and sex-matched non-atherosclerosis healthy subjects (n=28) were recruited from the local community (Harbin, P. R. China). The plasma was collected from each study subject and was subjected to metabolomics analysis by GC/MS. Pattern recognition analyses (principal components analysis, orthogonal partial least-squares discriminate analysis, and hierarchical clustering analysis) commonly demonstrated plasma metabolome, which was significantly different from atherosclerotic and non-atherosclerotic subjects. The development of atherosclerosis-induced metabolic perturbations of fatty acids, such as palmitate, stearate, and 1-monolinoleoylglycerol, was confirmed consistent with previous publication, showing that palmitate significantly contributes to atherosclerosis development via targeting apoptosis and inflammation pathways. Altogether, this study demonstrated that the development of atherosclerosis directly perturbed fatty acid metabolism, especially that of palmitate, which was confirmed as a phenotypic biomarker for clinical diagnosis of atherosclerosis.

Cough formation in viral infections in children

Using a multidisciplinary approach, Human Respiratory Viral Infections is set at the level between the definitive reference work and an essential clinical manual. Exploring recent advances in human respiratory viral research, the text builds on the basic sciences of epidemiology, virology, molecular biology, and immunology to cover clinical diagnosis, mechanism of pathogenesis, manifestations of disease, impact, treatment, and management strategies.

Theory-based self-management programs for promoting recovery in community-dwelling stroke survivors : a systematic review

Background Post-stroke recovery is demanding. Increasing studies have examined the effectiveness of self-management programs for stroke survivors. However no systematic review has been conducted to summarize the effectiveness of theory-based stroke self-management programs. Objectives The aim is to present the best available research evidence about effectiveness of theory-based self-management programs on community-dwelling stroke survivors’ recovery. Inclusion criteria Types of participants All community-residing adults aged 18 years or above, and had a clinical diagnosis of stroke. Types of interventions Studies which examined effectiveness of a self-management program underpinned by a theoretical or conceptual framework for community-dwelling stroke survivors. Types of studies Randomized controlled trials. Types of outcomes Primary outcomes included health-related quality of life and self-management behaviors. Secondary outcomes included physical (activities of daily living), psychological (self-efficacy, depressive symptoms), and social outcomes (community reintegration, perceived social support). Search Strategy A three-step approach was adopted to identify all relevant published and unpublished studies in English or Chinese. Methodological quality The methodological quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal checklist for experimental studies. Data Collection A standardized JBI data extraction form was used. There was no disagreement between the two reviewers on the data extraction results. Data Synthesis There were incomplete details about the number of participants and the results in two studies, which makes it impossible to perform meta-analysis. A narrative summary of the effectiveness of stroke self-management programs is presented. Results Three studies were included. The key issues of concern in methodological quality included insufficient information about random assignment, allocation concealment, reliability and validity of the measuring instruments, absence of intention-to-treat analysis, and small sample sizes. The three programs were designed based on the Stanford Chronic Disease Self-management program and were underpinned by the principles of self-efficacy. One study showed improvement in the intervention group in family and social roles three months after program completion, and work productivity at six months as measured by the Stroke Specific Quality of Life Scale (SSQOL). The intervention group also had an increased mean self-efficacy score in communicating with physicians six months after program completion. The mean changes from baseline in these variables were significantly different from the control group. No significant difference was found in time spent in aerobic exercise between the intervention and control groups at three and six months after program completion. Another study, using SSQOL, showed a significant interaction effect by treatment and time on family roles, fine motor tasks, self-care, and work productivity. However there was no significant interaction by treatment and time on self-efficacy. The third study showed improvement in quality of life, community participation, and depressive symptoms among the participants receiving the stroke self-management program, Stanford Chronic Disease Self-management program, or usual care six months after program completion. However, there was no significant difference between the groups. Conclusions There is inconclusive evidence about the effectiveness of theory-based stroke self-management programs on community-dwelling stroke survivors’ recovery. However the preliminary evidence suggests potential benefits in improving stroke survivors’ quality of life and self-efficacy.