Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.

OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. METHODS: Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes

EMPOWERED trial: protocol for a randomised control trial of digitally supported, highly personalised and measurement-based care to improve functional outcomes in young people with mood disorders

Objectives Many adolescents and young adults with emerging mood disorders do not achieve substantial improvements in education, employment, or social function after receiving standard youth mental health care. We have developed a new model of care referred to as 'highly personalised and measurement-based care' (HP&MBC). HP&MBC involves repeated assessment of multidimensional domains of morbidity to enable continuous and personalised clinical decision-making. Although measurement-based care is common in medical disease management, it is not a standard practice in mental health. This clinical effectiveness trial tests whether HP&MBC, supported by continuous digital feedback, delivers better functional improvements than standard care and digital support. Method and analysis This controlled implementation trial is a PROBE study (Prospective, Randomised, Open, Blinded End-point) that comprises a multisite 24-month, assessor-blinded, follow-up study of 1500 individuals aged 15-25 years who present for mental health treatment. Eligible participants will be individually randomised (1:1) to 12 months of HP&MBC or standardised clinical care. The primary outcome measure is social and occupational functioning 12 months after trial entry, assessed by the Social and Occupational Functioning Assessment Scale. Clinical and social outcomes for all participants will be monitored for a further 12 months after cessation of active care. Ethics and dissemination This clinical trial has been reviewed and approved by the Human Research Ethics Committee of the Sydney Local Health District (HREC Approval Number: X22-0042 & 2022/ETH00725, Protocol ID: BMC-YMH-003-2018, protocol version: V.3, 03/08/2022). Research findings will be disseminated through peer-reviewed journals, presentations at scientific conferences, and to user and advocacy groups. Participant data will be deidentified. Trial registration number ACTRN12622000882729

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

It Takes Two–Skilled Recognition of Objects Engages Lateral Areas in Both Hemispheres

Our object recognition abilities, a direct product of our experience with objects, are fine-tuned to perfection. Left temporal and lateral areas along the dorsal, action related stream, as well as left infero-temporal areas along the ventral, object related stream are engaged in object recognition. Here we show that expertise modulates the activity of dorsal areas in the recognition of man-made objects with clearly specified functions. Expert chess players were faster than chess novices in identifying chess objects and their functional relations. Experts' advantage was domain-specific as there were no differences between groups in a control task featuring geometrical shapes. The pattern of eye movements supported the notion that experts' extensive knowledge about domain objects and their functions enabled superior recognition even when experts were not directly fixating the objects of interest. Functional magnetic resonance imaging (fMRI) related exclusively the areas along the dorsal stream to chess specific object recognition. Besides the commonly involved left temporal and parietal lateral brain areas, we found that only in experts homologous areas on the right hemisphere were also engaged in chess specific object recognition. Based on these results, we discuss whether skilled object recognition does not only involve a more efficient version of the processes found in non-skilled recognition, but also qualitatively different cognitive processes which engage additional brain areas

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial

<p>Abstract</p> <p>Background</p> <p>Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo^®Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo^®Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline.</p> <p>Methods</p> <p>This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments.</p> <p>Discussions</p> <p>The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12610000576022.aspx">ACTRN12610000576022</a></p

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Missed injuries in trauma patients: A literature review

<p>Abstract</p> <p>Background</p> <p>Overlooked injuries and delayed diagnoses are still common problems in the treatment of polytrauma patients. Therefore, ongoing documentation describing the incidence rates of missed injuries, clinically significant missed injuries, contributing factors and outcome is necessary to improve the quality of trauma care. This review summarizes the available literature on missed injuries, focusing on overlooked muscoloskeletal injuries.</p> <p>Methods</p> <p>Manuscripts dealing with missed injuries after trauma were reviewed. The following search modules were selected in PubMed: Missed injuries, Delayed diagnoses, Trauma, Musculoskeletal injuires. Three time periods were differentiated: (n = 2, 1980–1990), (n = 6, 1990–2000), and (n = 9, 2000-Present).</p> <p>Results</p> <p>We found a wide spread distribution of missed injuries and delayed diagnoses incidence rates (1.3% to 39%). Approximately 15 to 22.3% of patients with missed injuries had clinically significant missed injuries. Furthermore, we observed a decrease of missed pelvic and hip injuries within the last decade.</p> <p>Conclusion</p> <p>The lack of standardized studies using comparable definitions for missed injuries and clinically significant missed injuries call for further investigations, which are necessary to produce more reliable data. Furthermore, improvements in diagnostic techniques (e.g. the use of multi-slice CT) may lead to a decreased incidence of missed pelvic injuries. Finally, the standardized tertiary trauma survey is vitally important in the detection of clinically significant missed injuries and should be included in trauma care.</p