Attitudes, beliefs, behaviours and perspectives on barriers and enablers of Australian general practitioners towards non-drug interventions: A national survey

BACKGROUND: Many guidelines recommend non-drug interventions (NDIs) for managing common conditions in primary care. However, compared with drug interventions, NDIs are less widely known, promoted and used. We aim to (1) examine general practitioners' (GPs') knowledge, attitudes and practices for NDIs, including their use of the Royal Australian College of General Practitioners (RACGP) Handbook of Non-Drug Interventions (HANDI), and (2) identify factors influencing their use of NDIs and HANDI.METHODS: We conducted a web-based cross-sectional survey of practicing GP members in Australia during October-November 2022. The survey contained five sections: characteristics of GP; knowledge and use of NDIs; attitudes towards NDIs; barriers and enablers to using HANDI; and suggestions of NDIs and ideas to improve the uptake of NDIs in primary care.RESULTS: Of the 366 GPs who completed the survey, 242 (66%) were female, and 248 (74%) were ≥45 years old. One in three GPs reported that they regularly ('always') recommend NDIs to their patients when appropriate (34%), whereas one-third of GPs were unaware of HANDI (39%). GPs identified several factors that improve the uptake of HANDI, including 'access and integration of HANDI in clinical practice', 'content and support to use in practice' and 'awareness and training'.CONCLUSIONS: While many GPs are aware of the effectiveness of NDIs and often endorse their use, obstacles still prevent widespread adoption in primary care. The results of this survey can serve as a foundation for developing implementation strategies to improve the uptake of effective evidence-based NDIs in primary care.</p

Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma

Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds) of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81) and 7.93 (95% CI: 2.26, 27.82) greater for women and men with high sHER2 concentrations (≥ 6.60 ng/mL) vs. low sHER2 concentrations (≤ 1.85 ng/mL), respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer

Comparison of MRI lesion evolution in different central nervous system demyelinating disorders

Background and Objective: There are few studies that compare lesion evolution across different CNS demyelinating diseases, yet knowledge of this may be important for diagnosis and understanding differences in disease pathogenesis. We sought to compare MRI T2-lesion evolution in myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD), and multiple sclerosis (MS). Methods: In this descriptive study, we retrospectively identified Mayo Clinic patients with MOGAD, AQP4-IgG-NMOSD, or MS and: 1) brain or myelitis attack; 2) available attack MRI within 6 weeks; and 3) follow-up MRI beyond 6 months without interval relapses in that region. Two neurologists identified the symptomatic or largest T2-lesion for each patient (index lesion). MRIs were then independently reviewed by two neuroradiologists blinded to diagnosis to determine resolution of T2-lesions by consensus. The index T2-lesion area was manually outlined acutely and at follow-up to assess variation in size. Results: We included 156 patients (MOGAD, 38; AQP4-IgG-NMOSD, 51; MS, 67) with 172 attacks (brain, 81; myelitis, 91). The age (median [range]) differed between MOGAD (25 [2-74]), AQP4-IgG-NMOSD (53 [10-78]) and MS (37 [16-61]) (p&lt;0.01) and female sex predominated in the AQP4-IgG-NMOSD (41/51 [80%]) and MS (51/67 [76%]) groups but not among those with MOGAD (17/38 [45%]). Complete resolution of the index T2-lesion was more frequent in MOGAD (brain, 13/18[72%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 3/21[14%]; spine, 0/34[0%]) and MS (brain, 7/42[17%]; spine, 0/29[0%]), p&lt;0.001. Resolution of all T2-Lesions occurred most often in MOGAD (brain, 7/18[39%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 2/21[10%]; spine, 0/34[0%]), and MS (brain, 2/42[5%]; spine, 0/29[0%]), p&lt; 0.01. There was a larger median (range) reduction in T2-lesion area in mm2 on follow-up axial brain MRI with MOGAD (213[55-873]) than AQP4-IgG-NMOSD (104[0.7-597]) (p=0.02) and MS, 36[0-506]) (p&lt; 0.001) and the reductions in size on sagittal spine MRI follow-up in MOGAD (262[0-888]) and AQP4-IgG-NMOSD (309[0-1885]) were similar (p=0.4) and greater than MS (23[0-152]) (p&lt;0.001)

Control of Centrin Stability by Aurora A

Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Clinical trials and their impact on policy during COVID-19: a review [version 1; peer review: 2 approved]

BACKGROUND: Of over 8,000 recorded randomised trials addressing COVID-19, around 80% were of treatments, and 17% have reported results. Approximately 1% were adaptive or platform trials, with 25 having results available, across 29 journal articles and 10 preprint articles.METHODS: We conducted an extensive literature review to address four questions about COVID-19 trials, particularly the role and impact of platform/adaptive trials and lessons learned.RESULTS: The key findings were: Q1. Social value in conducting trials and uptake into policy? COVID-19 drug treatments varied substantially and changed considerably, with drugs found effective in definitive clinical trials replacing unproven drugs. Dexamethasone has likely saved ½-2 million lives, and was cost effective across a range of countries and populations, whereas the cost effectiveness of remdesivir is uncertain. Published economic and health system impacts of COVID-19 treatments were infrequent. Q2. Issues with adaptive trial designs. Of the 77 platform trials registered, 6 major platform trials, with approximately 50 treatment arms, recruited ~135,000 participants with funding over $100 million. Q3. Models of good practice. Streamlined set-up processes such as flexible and fast-track funding, ethics, and governance approvals are vital. To facilitate recruitment, simple and streamlined research processes, and pre-existing research networks to coordinate trial planning, design, conduct and practice change are crucial to success. Q4. Potential conflicts to avoid? When treating patients through trials, balancing individual and collective rights and allocating scarce resources between healthcare and research are challenging. Tensions occur between commercial and non-commercial sectors, and academic and public health interests, such as publication and funding driven indicators and the public good. CONCLUSION: There is a need to (i) reduce small, repetitive, single centre trials, (ii) increase coordination to ensure robust research conducted for treatments, and (iii) a wider adoption of adaptive/platform trial designs to respond to fast-evolving evidence landscape.</p

Examining Australian’s beliefs, misconceptions and sources of information for COVID-19: a national online survey

OBJECTIVE: Public cooperation to practise preventive health behaviours is essential to manage the transmission of infectious diseases such as COVID-19. We aimed to investigate beliefs about COVID-19 diagnosis, transmission and prevention that have the potential to impact the uptake of recommended public health strategies. DESIGN: An online cross-sectional survey. PARTICIPANTS: A national sample of 1500 Australian adults with representative quotas for age and gender provided by an online panel provider. MAIN OUTCOME MEASURE: Proportion of participants with correct/incorrect knowledge of COVID-19 preventive behaviours and reasons for misconceptions. RESULTS: Of the 1802 potential participants contacted, 289 did not qualify, 13 declined and 1500 participated in the survey (response rate 83%). Most participants correctly identified 'washing your hands regularly with soap and water' (92%) and 'staying at least 1.5 m away from others' (90%) could help prevent COVID-19. Over 40% (incorrectly) considered wearing gloves outside of the home would prevent them from contracting COVID-19. Views about face masks were divided. Only 66% of participants correctly identified that 'regular use of antibiotics' would not prevent COVID-19.Most participants (90%) identified 'fever, fatigue and cough' as indicators of COVID-19. However, 42% of participants thought that being unable to 'hold your breath for 10 s without coughing' was an indicator of having the virus. The most frequently reported sources of COVID-19 information were commercial television channels (56%), the Australian Broadcasting Corporation (43%) and the Australian Government COVID-19 information app (31%). CONCLUSIONS: Public messaging about hand hygiene and physical distancing to prevent transmission appears to have been effective. However, there are clear, identified barriers for many individuals that have the potential to impede uptake or maintenance of these behaviours in the long term. We need to develop public health messages that harness these barriers to improve future cooperation. Ensuring adherence to these interventions is critical

Clinical trials and their impact on policy during COVID-19: a review

This review answers four main questions about clinical trials and their impact on policy during COVID-19 pandemic: 1. Clear relationship between social value in conducting trials and uptake into policy making, especially in an emergency context; 2. Are there particular issues with adaptive/platform trial designs that need to be considered – i.e. not the ‘gold standard’, weight of evidence?; 3. Are there models of good practice we can learn from? From past outbreaks, from COVID, more generally?; 4. What are some of the potential conflicts we need to avoid

Masked Analysis of the Clinical Utility of Commercially Available Antiretinal and Anti-Optic Nerve Antibody Testing

The clinical utility of most antiretinal and anti-optic nerve antibodies currently available for commercial testing remains unclear and unproven. Despite this, the presence of antiretinal antibodies is included in current diagnostic autoimmune retinopathy criteria, and the presence of anti-optic antibodies are often used to confirm a diagnosis of autoimmune optic neuropathy. However, there is no gold standard for these autoantibodies and it remains unclear how common these antibodies are in individuals without autoimmune retinopathy or optic neuropathy. Therefore, the goal of this study was to evaluate the clinical significance of comprehensiveantiretinal and anti-optic nerve antibody evaluations currently offered in North America