There is considerable variability in disease progression for patients with amyotrophic lateral sclerosis (ALS) including the age of disease onset, site of disease onset, and survival time. There is growing evidence that short structural variations (SSVs) residing in frequently overlooked genomic regions can contribute to complex disease mechanisms and can explain, in part, the phenotypic variability in ALS patients. Here, we discuss SSVs recently characterized by our laboratory and how these discoveries integrate into the current literature on ALS, particularly in the context of application to future clinical trials. These markers may help to identify and differentiate patients for clinical trials that have a similar ALS disease mechanism(s), thereby reducing the impact of participant heterogeneity. As evidence accumulates for the genetic markers discovered in SQSTM1 , SCAF4 , and STMN2 , we hope to improve the outcomes of future ALS clinical trials.
Prostate cancer is a complex disease affecting millions of men globally. Radiotherapy (RT) is a common treatment modality although treatment efficacy is dependent upon several features within the tumour microenvironment (TME), especially hypoxia. A hypoxic TME heightens radioresistance and thus disease recurrence and treatment failure continues to pose important challenges. However, the TME evolves under the influence of factors in systemic circulation and cellular crosstalk, underscoring its potential to be acutely and therapeutically modified. Early preclinical evidence suggests exercise may affect tumour growth and some of the benefits drawn, could act to radiosensitise tumours to treatment. Intracellular perturbations in skeletal muscle reactive oxygen species (ROS) stimulate the production of numerous factors that can exert autocrine, paracrine, and endocrine effects on the prostate. However, findings supporting this notion are limited and the associated mechanisms are poorly understood. In light of this preclinical evidence, we propose systemic changes in redox signalling with exercise activate redox-sensitive factors within the TME and improve tumour hypoxia and treatment outcomes, when combined with RT. To this end, we suggest a connection between exercise, ROS and tumour growth kinetics, highlighting the potential of exercise to sensitise tumour cells to RT, and improve treatment efficacy.
Background Artificial intelligence (AI) is defined as the study of algorithms that allow machines to reason and perform cognitive functions such as problem-solving, objects, images, word recognition, and decision-making. This study aimed to review the published articles and the comprehensive clinical relevance of AI-based tools used before, during, and after knee arthroplasty. Methods The search was conducted through PubMed, EMBASE, and MEDLINE databases from 2000 to 2021 using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA). Results A total of 731 potential articles were reviewed, and 132 were included based on the inclusion criteria and exclusion criteria. Some steps of the knee arthroplasty procedure were assisted and improved by using AI-based tools. Before surgery, machine learning was used to aid surgeons in optimizing decision-making. During surgery, the robotic-assisted systems improved the accuracy of knee alignment, implant positioning, and ligamentous balance. After surgery, remote patient monitoring platforms helped to capture patients’ functional data. Conclusion In knee arthroplasty, the AI-based tools improve the decision-making process, surgical planning, accuracy, and repeatability of surgical procedures.
Drinking water quality remains a persistent challenge across regional and remote Australia. We reviewed public reporting by 177 utilities and conducted a national assessment of reported exceedances against the health-based and aesthetic guideline values of the Australian Drinking Water Guidelines (ADWG). Four definitions of a basic level of drinking water quality were tested to quantify service gaps across regional and remote areas of each subnational jurisdiction in 2018–2019. At least 25,245 people across 99 locations with populations <1000 reportedly accessed water services that did not comply with health-based guideline values. Including larger towns and water systems, the estimated service gap rises to at least 194,572 people across more than 115 locations. Considering health parameters and the ADWG definition of ‘good’ aesthetic characteristics, the reported service gap rises further to at least 627,736 people across 408 locations. Forty percent of all locations with recorded health exceedances were remote Indigenous communities. Monitoring and reporting gaps indicate that the actual incidence of non-compliance with the guideline values of the ADWG could be much higher than our estimates. Our results quantified the divergence in the assessment of water quality outcomes between Sustainable Development Goal Target 6.1 and the ADWG, demonstrated disparities between service levels in capital cities and the rest of Australia, and highlighted the need for place-based solutions. The methods and dataset provide a ‘proof-of-concept’ for an Australian national drinking water quality database to guide government investments in water services.
This narrative review describes efforts to improve the care and prevention of fragility fractures in New Zealand from 2012 to 2022. This includes development of clinical standards and registries to benchmark provision of care, and public awareness campaigns to promote a life-course approach to bone health. Purpose: This review describes the development and implementation of a systematic approach to care and prevention for New Zealanders with fragility fractures, and those at high risk of first fracture. Progression of existing initiatives and introduction of new initiatives are proposed for the period 2022 to 2030. Methods: In 2012, Osteoporosis New Zealand developed and published a strategy with objectives relating to people who sustain hip and other fragility fractures, those at high risk of first fragility fracture or falls and all older people. The strategy also advocated formation of a national fragility fracture alliance to expedite change. Results: In 2017, a previously informal national alliance was formalised under the Live Stronger for Longer programme, which includes stakeholder organisations from relevant sectors, including government, healthcare professionals, charities and the health system. Outputs of this alliance include development of Australian and New Zealand clinical guidelines, clinical standards and quality indicators and a bi-national registry that underpins efforts to improve hip fracture care. All 22 hospitals in New Zealand that operate on hip fracture patients currently submit data to the registry. An analogous approach is ongoing to improve secondary fracture prevention for people who sustain fragility fractures at other sites through nationwide access to Fracture Liaison Services. Conclusion: Widespread participation in national registries is enabling benchmarking against clinical standards as a means to improve the care of hip and other fragility fractures in New Zealand. An ongoing quality improvement programme is focused on eliminating unwarranted variation in delivery of secondary fracture prevention.
Purpose To assess whether intraabdominal hypertension (IAH) may influence kidney failure as well as mortality. Methods This post-hoc analysis of two databases (IROI and iSOFA study) tested the independent association between IAH and kidney failure. Mortality was assessed using four prespecified groups (IAH present, kidney failure present, IAH and kidney failure present and no IAH or kidney failure present). Results Of 825 critically ill patients, 302 (36.6%) developed kidney failure and 192 (23.7%) died during the first 90 days. Only ‘Cumulative days with IAH grade II or more’ was significantly associated with kidney failure (OR 1.29 (1.08–1.55), p = 0.003) while ‘cumulative days with IAH grade I or more’ (p = 0.135) or highest daily IAP (p = 0.062) was not. IAH combined with kidney failure was independently associated with 90-day mortality (OR 2.20 (1.20–4.05), p = 0.011), which was confirmed for higher grades of IAH (grade II or more) alone (OR 2.14 (1.07–4.30), p = 0.032) and combined with kidney failure (OR 3.25 (1.72–6.12), p < 0.001). Conclusions This study suggest that duration as well as higher grades of IAH are associated with kidney failure and may increase mortality.
Body re-sizing illusions can profoundly alter perception of our own body. We investigated whether creating the illusion of a muscled and fit-looking back (Strong) influenced perceived back size, body ownership, and attitudes towards self-capacity during a lifting task. Twenty-four healthy male volunteers performed a standardised lifting task while viewing real-time (delay < 20 ms) video of their own back through a head-mounted display under four different conditions (Normal size, Strong, Reshaped, Large; order randomised). The MIRAGE-mediated reality system was used to modify the shape, size, and morphology of the back. Participants were poor at recognizing the correct appearance of their back, for both implicit (perceived width of shoulders and hips) and explicit (questionnaire) measures of back size. Visual distortions of body shape (Reshaped condition) altered implicit back size measures. However, viewing a muscled back (Strong condition) did not result in a sense of agency or ownership and did not update implicit perception of the back. No conditions improved perceptions/attitudes of self-capacity (perceived back strength, perceived lifting confidence, and perceived back fitness). The results lend support for the importance of the embodiment of bodily changes to induce changes in perception. Further work is warranted to determine whether increased exposure to illusory changes would alter perceptions and attitudes towards self-capacity or whether different mechanisms are involved.
Background B mode ultrasound (US) and shear wave elastography (SWE) are easily accessible imaging tools for idiopathic inflammatory myopathies (IIM) but require further validation against standard diagnostic procedures such as MRI and muscle biopsy. Methods In this prospective cross-sectional study we compared US findings to MRI and muscle biopsy findings in a group of 18 patients (11 F, 7 M) with active IIM (dermatomyositis 6, necrotising autoimmune myopathy 7, inclusion body myositis 4, overlap myositis 1) who had one or both procedures on the same muscle. US domains (echogenicity, fascial thickness, muscle bulk, shear wave speed and power doppler) in the deltoid and vastus lateralis were compared to MRI domains (muscle oedema, fatty infiltration/atrophy) and muscle biopsy findings (lymphocytic inflammation, myonecrosis, atrophy and fibro-fatty infiltration). A composite index score (1–4) was also used as an arbitrary indicator of overall muscle pathology in biopsies. Results Increased echogenicity correlated with the presence of fatty infiltration/atrophy on MRI (p = 0.047) in the vastus lateralis, and showed a non-significant association with muscle inflammation, myonecrosis, fibrosis and fatty infiltration/atrophy (p > 0.333) Severe echogenicity also had a non-significant association with higher composite biopsy index score in the vastus lateralis (p = 0.380). SWS and US measures of fascial thickness and muscle bulk showed poor discrimination in differentiating between pathologies on MRI or muscle biopsy. Power Doppler measures of vascularity correlated poorly with the presence of oedema on MRI, or with inflammation or fatty infiltration on biopsy. Overall, US was sensitive in detecting the presence of muscle pathology shown on MRI (67–100%) but showed poorer specificity (13–100%). Increased echogenicity showed good sensitivity when detecting muscle pathology (100%) but lacked specificity in differentiating muscle pathologies (0%). Most study participants rated US as the preferred imaging modality. Conclusions Our findings show that US, in particular muscle echogenicity, has a high sensitivity, but low specificity, for detecting muscle pathology in IIM. Traditional visual grading scores are not IIM-specific and require further modification and validation. Future studies should continue to focus on developing a feasible scoring system, which is reliable and allows translation to clinical practice.
Background The gender differences in demographic and clinical characteristics were examined in patients with hepatitis B virus (HBV)-related liver diseases. Methods Overall, 634 patients (44.7 ± 13.8 years) were consecutively included. Data of demographic and clinical characteristics were collected during an assessment interview. Comparisons between male and female patients in terms of demographic and clinical data were carried out using univariate analyses. The independent associations between the demographic and clinical variables and gender were examined with either logistic regression or analysis of covariance as appropriate. Results The study sample consisted of 452 male and 182 female patients. Multiple logistic regression analyses revealed that being employed (OR = 3.4), personal monthly income <3,000 yuan (OR = 0.3), being current alcohol users (OR = 6.4), Cirrhosis (OR = 5.9), Hepatocellular Carcinoma (HCC) (OR = 8.5) and having less severe insomnia (OR = 0.6) were independently associated with male gender. The analysis of covariance revealed that after controlling for other potential confounding variables, later onset of HBV-related diseases ( F = 4.5, p = 0.03) and older age ( F = 6.7, p = 0.009) were independently associated with male gender. Conclusions Given the significant clinical differences in male and female patients with HBV-related liver diseases, more attention should be given to gender-specific treatment and prevention for this population.
This research reports an exploratory study of 22 pre-service teachers involved in the Religious Education courses offered by The University of Notre Dame Australia, as part of the university’s accreditation to teach religious education. The study examined the influence of key factors on how confident these pre-service teachers perceived themselves to be to engage with the necessary knowledge to effectively teach religious education in a Catholic school. The pre-service teachers were surveyed pre and post their final-year internship, and subsequently, six of these were interviewed at the end of their first term of employment. Results indicated that out of the five compulsory courses, the two teaching method courses were found to be most influential in developing confidence to teach. Family, religious background, schooling, and mentoring were found to be influential in confidence development. In addition, confidence improved across the timeframe
Objective Mental Health Acts (MHAs) are important pieces of legislation which include essential definitions of mental illness and mental disorder and are used to guide decision-making regarding treatment, including involuntary admissions. In Australia, responsibility for reviewing this legislation falls under the jurisdiction of State and Territory Governments, resulting in interstate variations of legislative definitions and care requirements. In this paper, we outline some of the main differences between MHAs, and argue that it is time for Australia to enact nationally consistent Mental Health Legislation. Conclusions Substantial divergence exists between definitions of mental illness and mental disorder, differing criteria for involuntary treatment and discrepancies between treatment requirements for Indigenous Australians. While variations between MHAs are understandable considering the historical context, in an increasingly integrated society, it is time for Australia to enact nationally consistent mental health legislation.
Objectives Co-existence of mental and physical health conditions is prevalent. To achieve optimal physical therapy outcomes, neither should be treated in isolation. This review aims to map intersections between physical therapy and mental health. Methods Scoping review searching MEDLINE, CINAHL, PsycInfo, Cochrane and PEDro databases. Two independent researchers screened studies of physical therapy practice with adolescents/adults with mental health disorders or research using primary mental health outcomes in physical health conditions or clinicians’ perspective. Data were extracted on study type, participants, topics, publication year and country. Results The search yielded 3633 studies with 135 included. Five studies included adolescents. More than half were published since 2015. Studies specific to participants with mental health diagnoses included schizophrenia (n = 12), depressive disorders (n = 8), eating disorders (n = 6), anxiety disorders (n = 4), bipolar disorders (n = 1), somatic disorders (n = 5), and trauma and stressor-related disorders (n = 8) or varied mental health diagnoses (n = 14). Forty-one studies had primary mental health outcomes or clinical practice approaches with a mental health emphasis with participants with physical health conditions (musculoskeletal [n = 13], neurological [n = 7], other [n = 21]). Systematic reviews or randomized controlled trials predominantly involved exercise therapy and/or physical activity. Descriptions of physical therapists as participants (n = 35) included 4 main topics: (1) mental health screening; (2) knowledge, attitudes, and experiences; (3) key practice components; and (4) research priorities. Conclusions Physical therapy intersects with people experiencing mental health disorders across a broad spectrum of diagnoses, covering a range of interventions with a small but growing evidence base. Impact Exercise and physical activity studies dominated the highest levels of evidence and future focus although economic evaluations and consumer-driven or patient experience studies are needed. There is a contrast between the confidence and knowledge of specialized physical therapists working within mental health settings and those in general practice settings. Inspiring, integrated education is required to further improve healthcare outcomes following physical therapy for people with mental health disorders or symptoms.
While patients value engagement concerning their spirituality as a part of holistic healthcare, there is little evidence regarding the preferred way to engage in discussions about spirituality. This study investigated inpatient preferences regarding how they would like spirituality to be raised in the hospital setting. A cross-sectional survey was conducted with inpatients at six hospitals in Sydney, Australia ( n = 897), with a subset invited to participate in qualitative interviews ( n = 41). There was high approval for all proposed spiritual history prompts (94.0–99.8%). In interviews, the context dictated the appropriateness of discussions. Findings indicated a high level of patient acceptability for discussing spirituality in healthcare. Further research and more detailed analysis is required and proposed to be undertaken.
Importance: The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear. Objective: To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain. Design, setting, and participants: This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020. Interventions: Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation. Main outcomes and measures: The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point. Results: Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of -1.0 point ([95% CI, -1.5 to -0.4]; P = .001), favoring the intervention group. Conclusions and relevance: In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings. Trial registration: ANZCTR Identifier: ACTRN12615000610538.
Purpose A lack of published epidemiological data among police recruits presents a major challenge when designing appropriate prevention programs to reduce injury burden. We aimed to report the injury epidemiology of Western Australian (WA) Police Force recruits and examine sex and age as injury risk factors. Methods Retrospective analyses were conducted of prospectively collected injury data from WA Police Force recruits between 2018–2021. Injury was defined as ‘time-loss’ and injury incidence rate per 1000 training days (Poisson exact 95% confidence intervals) was calculated. For each region and type of injury, the incidence, severity, and burden were calculated. The association between age, sex, and injury occurrence were assessed using Cox regression time-to-event analysis. Results A total of 1316 WA Police Force recruits were included, of whom 264 recruits sustained 304 injuries. Injury prevalence was 20.1% and the incidence rate was 2.00 (95%CI 1.78–2.24) injuries per 1000 training days. Lower limb injuries accounted for most of the injury burden. Ligament/ joint injuries had the highest injury tissue/pathology burden. The most common activity injuring recruits was physical training (31.8% of all injuries). Older age (Hazard Ratio = 1.5, 95%CI = 1.2 to 1.9, p = 0.002) and female sex (Hazard Ratio = 1.4, 95%CI = 1.3 to 1.6, p < 0.001) increased risk of injury. Conclusion Prevention programs targeting muscle/tendon and ligament/joint injuries to the lower limb and shoulder should be prioritised to reduce the WA Police Force injury burden. Injury prevention programs should also prioritise recruits who are over 30 years of age or of female sex, given they are a higher risk population.
Despite an increased focus on ways to improve implementation of evidence and de‐implementation of practices with no known benefit, there is limited guidance on how to sustain these improvements. This review provides an introduction to sustainability of improvements in care and sustainability research, discussing how to support sustainability in practice and detailing a sustainability research agenda for the emergency medicine setting.
We examined three common sources of teacher stress (workload, student behavior, expectation stress) to identify teacher and school profiles. Data from the Teaching and Learning International Survey (TALIS) 2018 were used (n = 3117 teachers from 255 Australian schools). Latent profile analysis (LPA) revealed five teacher profiles: Low-Burden (17%), Mixed-Burden-Workload (15%), Mixed-Burden-Behavior (19%), Average-Burden (41%), and High-Burden (18%). Multilevel LPA identified three school profiles: Lower Pressure Climate (Workload) (17%), Lower Pressure Climate (Behavior) (23%), and Higher Pressure Climate (59%). The profiles were associated differently with background characteristics and work-related outcomes (strain, occupational commitment). Findings provide directions for efforts to support teachers.
A virtual workshop was organized by the Heart Valve Collaboratory to identify areas of expert consensus, areas of disagreement, and evidence gaps related to bioprosthetic aortic valve hemodynamics. Impaired functional performance of bioprosthetic aortic valve replacement is associated with adverse patient outcomes; however, this assessment is complicated by the lack of standardization for labelling, definitions, and measurement techniques, both after surgical and transcatheter valve replacement. Echocardiography remains the standard assessment methodology because of its ease of performance, widespread availability, ability to do serial measurements over time, and correlation with outcomes. Management of a high gradient after replacement requires integration of the patient’s clinical status, physical examination, and multimodality imaging in addition to shared patient decisions regarding treatment options. Future priorities that are underway include efforts to standardize prosthesis sizing and labelling for both surgical and transcatheter valves as well as trials to characterize the consequences of adverse hemodynamics.
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