Knowledge and Use of The ‘Clinical Framework For the Delivery of Health Services’ in Western Australia: Summary report of a survey of Workers’ Compensation stakeholders

The Clinical Framework for the Delivery of Health Services (Clinical Framework) provides guiding principles for the management of injured works based on contemporary evidence. As part of an “Injured Worker Symposium” hosted by Curtin University in March this year, 161 stakeholders from variety of roles, who deal with injured workers in the Western Australian Workers’ Compensation sector, completed an online questionnaire. This questionnaire collected stakeholder perspectives regarding the Clinical Framework, barriers and enablers for timely recovery of injured workers, and understanding of the biopsychosocial management of workers with musculoskeletal pain disorders. The study found that 43% of respondents were ‘not familiar’ with the Clinical Framework. Another 32% were only ‘somewhat familiar’. This suggests that further work is required to educate stake holders on the existence and utility of the Clinical Framework. There was strong agreement among the different stakeholder groups regarding the key importance of communication between stakeholders and the employer-employee relationship to the recovery of injured workers. While this is a preliminary survey and the results need to be interpreted with some caution, the findings of the survey support that further stakeholder education is required in a number of areas related to the Clinical Framework. This document provides a summary and interpretation of the survey results and recommendations for further research and education, based on the findings of the study

Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration

Degeneration of the spinal discs is a major cause of back pain. During the degeneration process, there is a loss of glycosaminoglycans (GAGs) from the proteoglycan-rich gel in the disc’s nucleus, which adversely alters biomechanical performance. Current surgical treatments for back pain are highly invasive and have low success rates; there is an urgent need for minimally-invasive approaches that restore the physiological mechanics of the spine. Here we present an injectable peptide:GAG hydrogel that rapidly self-assembles in situ and restores the mechanics of denucleated intervertebral discs. It forms a gel with comparable mechanical properties to the native tissue within seconds to minutes depending on the peptide chosen. Unlike other biomaterials that have been proposed for this purpose, these hybrid hydrogels can be injected through a very narrow 25 G gauge needle, minimising damage to the surrounding soft tissue, and they mimic the ability of the natural tissue to draw in water by incorporating GAGs. Furthermore, the GAGs enhance the gelation kinetics and thermodynamic stability of peptide hydrogels, significantly reducing effusion of injected material from the intervertebral disc (GAG leakage of 8 ± 3% after 24 hrs when peptide present, compared to 39 ± 3% when no peptide present). In an ex vivo model, we demonstrate that the hydrogels can restore the compressive stiffness of denucleated bovine intervertebral discs. Compellingly, this novel biomaterial has the potential to transform the clinical treatment of back pain by resolving current surgical challenges, thus improving patient quality of life

Brief biopsychosocially informed education can improve insurance workers' back pain beliefs: Implications for improving claims management behaviours

Background: Biopsychosocially informed education is associated with improved back pain beliefs and positive changes in health care practitioners’ practice behaviours. Objective: Assess the effect of this type of education for insurance workers who are important non-clinical stakeholders in the rehabilitation of injured workers. Methods: Insurance workers operating in the Western Australian workers’ compensation system underwent two, 1.5 hour sessions of biopsychosocially informed education focusing on understanding and identifying barriers to recovery of injured workers with musculoskeletal conditions. Back pain beliefs were assessed pre-education, immediately post-education and at three-month follow-up (n = 32). Self-reported and Injury Management Advisor-reported assessment of change in claims management behaviours were collected at the three-month follow-up. Results: There were positive changes in the Health Care Providers’ Pain and Impairment Relationship Scale (p = 0.009) and Back Beliefs Questionnaire (p = 0.049) immediately following the education that were sustained at three-month follow-up. Positive changes in claims management behaviours were supported by self-reported and Injury Management Advisor-reported data. Conclusion: This study provides preliminary support that a brief biopsychosocially informed education program can positively influence insurance workers’ beliefs regarding back pain, with concurrent positive changes in claims management behaviours. Further research is required to ascertain if these changes result in improved claims management outcomes

An investigation of the nature of fear within ACL-injured subjects when exposed to provocative videos: a concurrent qualitative and quantitative study

Fear is a factor contributing to poor return to sport after an anterior cruciate (ACL) injury, however the identification and assessment of fear is challenging. To improve understanding of fear, this study qualitatively and quantitatively assessed responses to videos depicting threat to knee stability in people who had experienced an ACL injury. ACL-injured participants who had above average fear on the Tampa Scale of Kinesiophobia and were at least 1-year post-injury/surgery were eligible. Participants were shown four videos depicting sequentially increasing threat to their knee stability (running, cut-and-pivot, feigned knee injury during cut-and-pivot, series of traumatic knee injuries). Qualitative interviews explored participants feeling related to viewing the videos. Participants quantitatively self-rated fear and distress in response to each video. Seventeen participants were included in this study (71% female, with an average time since last ACL injury of 5 ½ years). Five themes were identified: (1) Evoked physiological responses, (2) Deeper contextualisation of the meaning of an ACL injury influencing bodily confidence, (3) Recall of psychological difficulties, (4) Negative implications of a re-injury, and (5) Change to athletic identity. Quantitatively, direct proportionality was noticed between threat level and reported fear and distress. Specifically, participants reported increasing levels of fear and distress as the videos progressed in threat level, with the largest increase seen between a cut-and-pivot movement to a feigned injury during a cut and pivot. The results support the notion that in addition to being a physical injury, an ACL injury has more complex neurophysiological, psychological, and social characteristics which should be considered in management. Using video exposure in the clinic may assist identification of underlying psychological barriers to recovery following an ACL injury, facilitating person-centred care

RPGR protein complex regulates proteasome activity and mediates store-operated calcium entry

Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L, cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton organization. The actin cytoskeleton rearrangement is regulated by the small GTPase RhoA via the planar cell polarity (PCP) pathway. RhoA activity was upregulated in the absence of RPGR, RPGRIP1 or RPGRIP1L proteins. In RPGR, RPGRIP1 or RPGRIP1L KD cells, we observed increased levels of DVl2 and DVl3 proteins, the core components of the PCP pathway, due to impaired proteasomal activity. RPGR, RPGRIP1 or RPGRIP1L KD cells treated with thapsigargin (TG), an inhibitor of sarcoendoplasmic reticulum Ca2+ - ATPases, showed impaired store-operated Ca2+ entry (SOCE), which is mediated by STIM1 and Orai1 proteins. STIM1 was not localized to the ER-PM junction upon ER store depletion in RPGR, RPGRIP1 or RPGRIP1L KD cells. Our results demonstrate that the RPGR protein complex is required for regulating proteasomal activity and for modulating SOCE, which may contribute to the ciliopathy phenotype

Participatory design of an infographic to help support the care of people living with complex regional pain syndrome

Background Complex regional pain syndrome (CRPS) can be a debilitating pain condition with enduring physical, psychological and social impacts. CRPS is often poorly understood by healthcare professionals and management needs to be tailored to each individual’s presentation. People with lived experience express difficulty in accessing reliable and meaningful information about the condition. This study aimed to co-create a trustworthy infographic to share information about the lived experience of CRPS. Methods We adopted a seven-phase, iterative, participatory methodology to co-create the infographic. Potential infographic content was obtained from qualitative work investigating the lived experience of CRPS. Online consumer engagement (people with doctor diagnosed CRPS/their family, n=20) was used to prioritise content to be included in the infographic and then potential designs were sourced. The research team narrowed the selections down to two designs which were presented to consumers online for final selection ( n=25) and refinement ( n=34). Results An infographic for understanding the lived experience of CRPS was completed using participatory design, providing a resource aligned to the needs of people with this condition. Using the Patient Education Materials Assessment Tool, the final infographic rated highly for understandability (92%) and participants indicated significant willingness to share this infographic with others (93%). Conclusion A process of participatory design was an effective and efficient process for translation of evidence gathered from qualitative research into a trustworthy resource for people with CRPS and their support people

Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects.

Primary ciliary dyskinesia (PCD) is an inherited chronic respiratory obstructive disease with randomized body laterality and infertility, resulting from cilia and sperm dysmotility. PCD is characterized by clinical variability and extensive genetic heterogeneity, associated with different cilia ultrastructural defects and mutations identified in >20 genes. Next generation sequencing (NGS) technologies therefore present a promising approach for genetic diagnosis which is not yet in routine use. We developed a targeted panel-based NGS pipeline to identify mutations by sequencing of selected candidate genes in 70 genetically undefined PCD patients. This detected loss-of-function RSPH1 mutations in four individuals with isolated central pair (CP) agenesis and normal body laterality, from two unrelated families. Ultrastructural analysis in RSPH1-mutated cilia revealed transposition of peripheral outer microtubules into the 'empty' CP space, accompanied by a distinctive intermittent loss of the central pair microtubules. We find that mutations in RSPH1, RSPH4A and RSPH9, which all encode homologs of components of the 'head' structure of ciliary radial spoke complexes identified in Chlamydomonas, cause clinical phenotypes that appear to be indistinguishable except at the gene level. By high-resolution immunofluorescence we identified a loss of RSPH4A and RSPH9 along with RSPH1 from RSPH1-mutated cilia, suggesting RSPH1 mutations may result in loss of the entire spoke head structure. CP loss is seen in up to 28% of PCD cases, in whom laterality determination specified by CP-less embryonic node cilia remains undisturbed. We propose this defect could arise from instability or agenesis of the ciliary central microtubules due to loss of their normal radial spoke head tethering

Low back pain in 17 year olds has substantial impact and represents an important public health disorder: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Prevalence of low back pain (LBP) rises rapidly during adolescence, reaching adult levels by the age of 18. It has been suggested that adolescent LBP is benign with minimal impact, despite limited evidence.</p> <p>Methods</p> <p>The aim of this study was to investigate the impact of LBP and the influence of chronicity, gender and presence of other spinal pain comorbidities at age 17. Subjects (n = 1283) were categorised according to experiencing current and chronic LBP, gender and presence of other areas of spinal pain. LBP impact was ascertained via questions regarding seeking professional assistance, using medication, missing school/work, limited normal or recreational physical activity and health related quality of life (HRQOL).</p> <p>Results</p> <p>12.3% of participants reported current but not chronic LBP, while 19.9% reported current chronic LBP. LBP was more commonly reported by females than males. Other spinal pain comorbidities were common in the LBP groups. Impact was greater in subjects with chronic LBP, in females and in those with other spinal pain comorbidities.</p> <p>Conclusion</p> <p>LBP, and particularly chronic LBP, has a significant negative impact at 17 years. It is commonly associated with care seeking, medication use, school absenteeism, and reduced HRQOL. These findings support that adolescent LBP is an important public health issue that requires attention.</p

Regulation of Retention of FosB Intron 4 by PTB

One effect of stressors such as chronic drug administration is that sequence within the terminal exon of the transcription factor FosB is recognized as intronic and removed by alternative splicing. This results in an open-reading-frame shift that produces a translation stop codon and ultimately a truncated protein, termed ΔFosB. In vitro splicing assays with control and mutated transcripts generated from a fosB mini-gene construct indicated a CU-rich sequence at the 3′ end of intron 4 (I4) plays an important role in regulating fosB pre-mRNA splicing due to its binding of polypyrimidine tract binding protein (PTB). PTB binding to this sequence is dependent upon phosphorylation by protein kinase A and is blocked if the CU-rich sequence is mutated to a U-rich region. When this mutated fosB minigene is expressed in HeLa cells, the splicing efficiency of its product is increased compared to wild type. Moreover, transient transfection of PTB-1 in HeLa cells decreased the splicing efficiency of a wild type fosB minigene transcript. Depletion of PTB from nuclear extracts facilitated U2AF65 binding to wild type sequence in vitro, suggesting these proteins function in a dynamic equilibrium to modulate fosB pre-mRNA alternative splicing. These results demonstrate for the first time that phosphorylated PTB promotes intron retention and thereby silences the splicing of fosB I4

Human genetics and clinical aspects of neurodevelopmental disorders

This chapter traverses contemporary understandings of the genetic architecture of human disease, and explores the clinical implications of the current state of knowledge. Many different classes of genetic mutations have been implicated as being involved in predisposition to certain diseases, and researchers are continually uncovering other means by which genetics plays an important role in human disease, such as with somatic genetic mosaicism. Putative “de novo” mutations can represent cases of parental mosaicism (including in the germline), which could be revealed by careful genotyping of parental tissues other than peripheral blood lymphocytes. There is an increasingly rich literature regarding rare mutations with seemingly large phenotypic effects. Privacy concerns have added to the difficulties of implementing genomics-guided medicine. With the advent of exome and whole genome sequencing (WGS), one needs to focus again on families over several generations, so as to attempt to minimize genetic differences, locus heterogeneity and environmental influences