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Inherited retinal diseases (IRDs) are a broad range of diseases associated with abnormalities/degeneration of retinal cells. We aimed to identify the top 10 Australian research priorities for IRDs to ultimately facilitate more meaningful and potentially cost-effective research.
We conducted a James Lind Alliance priority setting partnership that involved two Australian-wide surveys and online workshops.
Australia-wide.
Individuals aged 16 years or older were eligible to participate if they had an IRD, were caregivers of an individual with an IRD or were health professionals providing care to this community.
In Survey 1, we gathered participants’ unanswered questions about IRDs. We grouped these into summary questions and undertook a literature review to verify if they were truly unanswered (ie, evidence uncertainties). In Survey 2, participants voted for the uncertainties that they considered a priority. Top-ranked uncertainties progressed for discussion and final prioritisation in two workshops.
In Survey 1, we collected 223 questions from 69 participants. We grouped these into 42 summary questions and confirmed 41 as evidence uncertainties. In Survey 2, 151 participants voted, with the 16 uncertainties progressing to final prioritisation. The top 10 priorities, set by the 24 workshop participants, represented (1) treatment/cure; (2) symptoms and disease progression; (3) psychosocial well-being and (4) health service delivery. The #1 priority was for treatment to prevent, slow down or stop vision loss, followed by the #2 priority to address the psychological impact of having an IRD.
The top 10 research priorities highlight the need for IRD research that takes a whole-person, systems approach. Collaborations to progress priorities will accelerate the translation of research into real-world benefits.
by Drew Gorenz, Norbert Schwarz
People hear jokes live and pre-recorded in a variety of settings, from comedy clubs, bars, outdoor venues, cafes, to their own home or car. While a lot of research has analyzed the significance of the content of jokes, we know less about the significance of the setting one hears them in. Some settings can have interfering background noise or poor acoustics, reducing an audience’s ease of processing heard jokes. Would this affect how funny the jokes seem? Two experiments with audio clips of stand-up comedy performances show that participants found jokes less funny when background noise interfered with their listening.Cluster analysis, a machine learning-based and data-driven technique for identifying groups in data, has demonstrated its potential in a wide range of contexts. However, critical appraisal and reproducibility are often limited by insufficient reporting, ultimately hampering the interpretation and trust of key stakeholders. The present paper describes the protocol that will guide the development of a reporting guideline and checklist for studies incorporating cluster analyses—Transparent Reporting of Cluster Analyses.
Following the recommended steps for developing reporting guidelines outlined by the Enhancing the QUAlity and Transparency Of health Research Network, the work will be divided into six stages. Stage 1: literature review to guide development of initial checklist. Stage 2: drafting of the initial checklist. Stage 3: internal revision of checklist. Stage 4: Delphi study in a global sample of researchers from varying fields (n=) to derive consensus regarding items in the checklist and piloting of the checklist. Stage 5: consensus meeting to consolidate checklist. Stage 6: production of statement paper and explanation and elaboration paper. Stage 7: dissemination via journals, conferences, social media and a dedicated web platform.
Due to local regulations, the planned study is exempt from the requirement of ethical review. The findings will be disseminated through peer-reviewed publications. The checklist with explanations will also be made available freely on a dedicated web platform (troca-statement.org) and in a repository.
Post-intensive care syndrome (PICS) describes a cluster of ongoing symptoms experienced by a large proportion of patients previously admitted to critical care. Despite a large rise in survival following critical care, interventions to support recovery and combat PICS are lacking. It has been suggested that the use of digital tools such as virtual reality (VR) may play a useful role in the development of recovery-supporting interventions. We engaged with people with lived experience of critical care admission to coproduce a VR intervention (ViRtual REality to AiD recoverY post ICU (VR READY)). Here, we present a protocol for the initial feasibility and acceptability testing of this intervention.
This is a single-arm, single-site, non-randomised feasibility trial of VR READY. Up to 25 participants recently admitted to critical care will be recruited to use the VR READY intervention for at least 5 min per day for a period of 14 days. Participants must have capacity to consent and be free from ongoing delirium in order to participate. Outcomes relating to sleep and well-being will be measured at baseline and at day 14 after intervention delivery. The primary outcome is feasibility, which will be assessed according to prespecified criteria. Participants will complete a qualitative interview to assess acceptability of the intervention, trial design and outcomes approximately 1 month after completing the intervention period. No formal statistical analysis of outcomes will be conducted, but these will be summarised descriptively. Interviews will be subjected to reflexive thematic analysis.
This study received a favourable ethical opinion by North-East York Research Ethics Committee (Ref 23/NE/0113) in June 2024. Study results will be disseminated through the peer review literature, ISRCTN registry and directly to participants, which will be facilitated by the study public and patient involvement steering group.
Poor chest health is the leading cause of early mortality in children with cerebral palsy (CP). It is also the most common reason to seek healthcare, accruing significant costs and reducing quality-of-life for children and families. Clinical trials examining chest health interventions in CP are characterised by inconsistent outcome measures, limiting the capacity for evidence synthesis to inform clinical application. The study aims to develop a core outcome set (COS) and related measurement instruments to assess, monitor and evaluate chest health in children with CP, both in research and routine clinical practice. The COS will reflect the views of children, young people, parent/carers, clinicians and researchers, emphasising under-represented groups in research and those at risk of poorer chest health.
A 3-phase methodology will be conducted in line with the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. (1) Candidate outcomes will be identified through a qualitative evidence synthesis and interviews with key stakeholders. Findings will be mapped to COMET-taxonomy, generating a list of candidate outcomes. (2) An international e-Delphi survey will invite stakeholders to rate the importance of each outcome, followed by a consensus meeting to ratify the COS. (3) A structured review, guided by health measurement taxonomy, will evaluate relevant instruments, with a final meeting to agree on recommended measures for each COS domain.
Ethical approval was provided by the University of Plymouth Research Ethics Committee for the qualitative interview study (ID5116), e-Delphi study and consensus meeting (ID5636). Study findings will be published open access in a peer-reviewed journal and presented at relevant national and international conferences.
COMET registration: 2590 (https://www.comet-initiative.org/Studies/Details/2590)
CRD42024562735.
by Okkeun Jung, Angelene Soto, Andrew L. Wolfe, Shahana S. Mahajan
KRAS mutations, which induce proliferative signaling driving many human cancers, are detectable in a small subset of osteosarcoma patients. The recently developed pan-KRAS inhibitor daraxonrasib, also known as RMC-6236, is capable of targeting a wide array of KRAS mutations and shows promise against pancreatic and lung cancers. However, the efficacy and mechanisms of action of daraxonrasib in osteosarcoma (OS) remain unclear. We evaluated the effects of daraxonrasib on the viability, proliferation, and metastatic potential of wild-type and KRAS mutant OS cells. We assayed the effects of treatment on downstream targets using qPCR, immunoblotting, and activity assays to explore the underlying mechanism by which daraxonrasib selectively suppresses the metastatic potential of KRAS mutant osteosarcoma. Finally, we investigated how the increased prevalence of GTP-bound KRAS enhanced the sensitivity of KRAS wild-type osteosarcoma cells to daraxonrasib using siRNA targeting RASA1. Daraxonrasib selectively attenuated the proliferation and migratory ability of KRAS mutant HOS-143B cells without affecting KRAS wild-type controls. Additionally, daraxonrasib suppressed the expression of the matrix metalloproteases MMP9 and MMP1, which promote cell motility and metastasis. Daraxonrasib selectively inhibited the AKT/ETS1 pathway in HOS-143B cells, whereas no such effect was observed in HOS cells. HOS cells were sensitized to daraxonrasib by knocking down the GTPase-activating protein RASA1. In osteosarcoma, KRAS inhibition decreased MMP1, MMP9, and AKT/ETS1 signaling. Daraxonrasib is a promising agent for treating osteosarcoma with KRAS mutations.SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.
CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.
The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).
Breastfeeding is beneficial to the health of both the mother and infant. Despite recommendations to breastfeed by organisations including the WHO and the American Academy of Pediatrics, rates of breastfeeding remain below public health goals. The Mother and Infant Metabolome and Microbiome (MIMM) study is a prospective cohort study of healthy mother-term infant dyads designed to comprehensively assess the perinatal, maternal, neonatal and infant factors that are associated with breastfeeding outcomes and human milk composition.
MIMM participants were recruited from two medical centres in Boston, Massachusetts, from 2019 to 2023 and are followed for 2 years. Dyads were included if the mother delivered a singleton infant at ≥37 weeks’ gestation, was discharged home 2 and infant gestational age was 39.3 weeks. Approximately 43% of infants were born via caesarean delivery, and 45.5% were female.
MIMM study procedures include longitudinal (1) collections of maternal blood, vaginal swab, stool and milk and infant blood and stool samples and (2) assessments of breastfeeding status, child neurodevelopment and growth and maternal health at birth, 6 weeks and 6, 12, 18 and 24 months. Data collection through 18 months is complete. The overall objective of the MIMM study is to identify potential targets to improve breastfeeding outcomes, human milk composition and ultimately, maternal and child health. Preliminary analyses, reported in conference presentations (with ongoing analyses and results manuscripts pending), have found that (1) mothers with higher levels of stress were less likely to be exclusively breastfeeding their infants at 6 weeks; (2) higher breastfeeding intensity was associated with greater postpartum weight loss at 6 weeks; (3) feeding type was a more relevant predictor of feeding frequency and volume compared with feeding mode; (4) infants who received exclusive human milk had higher food enjoyment compared with those who received any formula; and (5) infants of mothers with obesity had higher average feeding volume per feed.
Data collection for the final 24-month visit is expected to be completed by August 2025. We expect that all sample assays will be completed by December 2025. Findings will continue to be submitted for presentation at scientific conferences, and we expect to publish the first findings from this cohort in manuscript format in 2025.
Closed incision negative pressure therapy (ciNPT) with foam dressings has received broad recognition for its ability to support incision healing for a variety of surgical procedures. Over time, these dressings have evolved to include linear and ‘area’ shapes to better conform to different incision types and surface geometries. To address new studies on these configurations and provide guidance for dressing selection, an international, multidisciplinary panel of experts was convened. The panel reviewed recent publications on ciNPT with reticulated open cell foam (ROCF) dressings, shared their cases and experiences and engaged in roundtable discussions on benefits, drawbacks and technical challenges. Topics were ranked by importance and refined into potential consensus statements. These were shared for anonymous feedback, requiring 80% agreement for consensus. This manuscript establishes 12 consensus statements regarding risk factors supporting the use of ciNPT, conditions supporting preference of linear or area ciNPT dressings and tips for practical application of ciNPT with ROCF dressings. While this consensus panel expands on previous publications to aid clinicians' decision-making, further research is needed to refine recommendations and identify the strengths and limitations of ciNPT. Continued multidisciplinary collaboration will ensure ciNPT remains vital for improving surgical outcomes and patient care.
by Karishma K. Singh, Andrew J. Elliot, Elizabeth D. Handley, Jeremy P. Jamieson
Individuals embody various social identities that can impact how they interface with the social environment. Stigma theories suggest that members of low-status or marginalized groups possess devalued social identities, and therefore, experience more stress. While social identities can lead to increased stress, individuals’ appraisals of their identities are not necessarily perceived as harmful/demanding. Rather, social identities can also be appraised as resources or sources of strength bringing opportunities and facilitating goal attainment. Using the biopsychosocial (BPS) model of challenge and threat as a conceptual foundation, this research developed a novel measure to assess individuals’ appraisals of their social identities. In Study 1 (N = 575), confirmatory factor analysis (CFA) evaluated the theorized factor structure (i.e., resource and demand appraisals) and assessed the overall fit of the model. Structural equation modeling (SEM) tested for associations between the resource and demand latent factors. Individuals appraising their ethnic-racial identity as a resource exhibited improved self and intergroup outcomes, while those perceiving it as a demand reported worse self-based and intergroup outcomes, as well as more distress. Study 2 (N = 743 Black and White Americans), which was preregistered, examined group differences in appraisals of ethnic-racial identity. SEM revealed that Black participants were more likely than White participants to appraise their ethnic-racial identity as demanding, leading to worse social and intergroup outcomes. Even when Black participants perceived their ethnic-racial identity as a resource, they still reported higher levels of discrimination, intergroup anxiety, and behavioral avoidance compared to their White counterparts. Implications for theory development and application to the stress literature are discussed.by Jack O. Thomas, Josiah K. To, Parsa Riazi Esfahani, Frithjof Kruggel, William C. Tang, Andrew W. Browne
PurposeThis study aims to explore the feasibility and performance of three-dimensional ultrasound (3DUS) imaging in ophthalmology using commercially available ultrasound probes adapted to a slit lamp.
SignificanceDespite ultrasound’s long-standing application in eye care for visualizing ocular components, the evolution of 3DUS technology has remained inactive, with limited development and commercial availability. This study introduces a novel method that could potentially enhance ophthalmic diagnostics and treatment planning by providing comprehensive 3D views of ocular structures using existing ultrasound probes adapted to the conventional slit lamp.
MethodsA custom system was designed for mounting a linear actuator to a slit lamp and enabling the horizontal actuation of any ultrasound probe. Ophthalmic and non-ophthalmic ultrasound probes were tested for their ability to reconstruct 3DUS images of the posterior pole. The study involved designing and evaluating three US phantoms ex vivo and performing in vivo imaging on human subjects to assess the system’s applicability.
ResultsThe system successfully acquired 3D volume scans of phantoms and live human eyes, demonstrating the system’s potential for detailed ocular imaging. The adaptability of the device allowed for compatibility with various ultrasound probes. In vivo imaging revealed the system’s capability to produce high-resolution 3D reconstructions of ocular structures, including eyes with pathological conditions.
ConclusionsThe introduction of a slit lamp-mounted 3DUS system represents a significant advancement in ophthalmic ultrasonography, offering a practical and accessible solution for comprehensive 3D ocular assessments. The device’s modularity and compatibility with existing ultrasound probes make it a versatile tool for a wide range of ophthalmic applications. Further research and clinical trials are needed to optimize the system’s performance and validate its clinical utility.
by Jasmine C. Mah, Olga Theou, Mario Ulises Perez-Zepeda, Jodie L. Penwarden, Judith Godin, Kenneth Rockwood, Melissa K. Andrew
BackgroundThe construct of social vulnerability attempts to understand social circumstances not merely as a descriptor, but as a predictor of adverse health events. It can be measured by aggregating social deficits in a social vulnerability index (SVI). We describe a standard procedure for constructing a multi-level SVI using two working examples.
MethodsFirst, we describe a six-step approach to constructing a SVI. Then, we conducted a secondary analysis of a clinical dataset (Canadian Immunization Research Network’s Serious Outcomes Surveillance Network (SOS)) and a population-based dataset (Canadian Longitudinal Study on Aging (CLSA)). In both datasets, we construct SVIs, use descriptive statistics to report distributions by age and sex, and perform a multivariable linear regression of social vulnerability on frailty.
ResultsProcedures for drafting a list of candidate social items, selecting deficits for inclusion, and screening deficits to meet inclusion criteria were applied to yield a 18-deficit SVI for the SOS and 74-deficit SVI for the CLSA. Deficits in each SVI were re-scored between 0 and 1, where 1 indicates the greater risk. Finally, the sum of all deficits is calculated into an index. In the SOS, SVI was associated with age only for females and was weakly associated with frailty (r = 0.26, p Conclusion
We present a standard method of constructing a SVI by incorporating factors from multiple social domains and levels in a social-ecological model. This SVI can be used to improve our understanding of social vulnerability and its impacts on the health of communities and individuals.
by Andrew D. Shelton, Jessica L. Allen, Vicki S. Mercer, Jeremy R. Crenshaw, Jason R. Franz
Rehabilitation to prevent falls should not only directly address intrinsic and extrinsic factors, but also the neuropsychology of falls to promote safe and independent mobility in our aging population. The purpose of this study was to determine the relation between falls self-efficacy and objective responses to a series of walking balance perturbations. 29 healthy younger adults and 28 older adults completed four experimental trials, including unperturbed walking and walking while responding to three perturbations: mediolateral optical flow, treadmill-induced slips, and lateral waist-pulls; and three self-reported questionnaires: Activity-specific Balance Confidence, Falls Efficacy Scale, and the Fear of Falling Questionnaire-Revised. We quantified stabilizing responses as a change in margin of stability from unperturbed walking. Older adults generally exhibited larger instability than younger adults in response to walking balance perturbations. Only the Fear of Falls Questionnaire-Revised showed an increase in perceived falls risk for older adults. We found no significant correlations for older adults between any balance perturbation response and questionnaires of self-perception. Given the disconnect between self-perceived falls risk and responses to walking balance perturbations, rehabilitation to prevent falls while maintaining mobility and independence will likely require personalized techniques that combine neuromuscular training with approaches for neurophysiological reeducation.by Lianyu Shan, Mojdeh Matloubi, Ifeoma Okwor, Sam Kung, Mohamed Sadek Almiski, Sujata Basu, Andrew Halayko, Latifa Koussih, Abdelilah S. Gounni
Dendritic cells (DCs) are pivotal in regulating allergic asthma. Our research has shown that the absence of Sema3E worsens asthma symptoms in acute and chronic asthma models. However, the specific role of PlexinD1 in these processes, particularly in DCs, remains unclear. This study investigates the role of PlexinD1 in CD11c+ DCs using a house dust mite (HDM) model of asthma. We generated CD11c+ DC-specific PlexinD1 knockout (CD11cPLXND1 KO) mice and subjected them, alongside wild-type controls (PLXND1fl/fl), to an HDM allergen protocol. Airway hyperresponsiveness (AHR) was measured using FlexiVent, and immune cell populations were analyzed via flow cytometry. Cytokine levels and immunoglobulin concentrations were assessed using mesoscale and ELISA, while collagen deposition and mucus production were examined through Sirius-red and periodic acid Schiff (PAS) staining respectively. Our results indicate that CD11cPLXND1 KO mice exhibit significantly exacerbated AHR, characterized by increased airway resistance and tissue elastance. Enhanced mucus production and collagen gene expression were observed in these mice compared to wild-type counterparts. Flow cytometry revealed higher CD11c+ MHCIIhigh CD11b+ cell recruitment into the lungs, and elevated total and HDM-specific serum IgE levels in CD11cPLXND1 KO mice. Mechanistically, co-cultures of B cells with DCs from CD11cPLXND1 KO mice showed significantly increased IgE production compared to wild-type mice.These findings highlight the critical regulatory role of the plexinD1 signaling pathway in CD11c+ DCs in modulating asthma features.The objective of this paper was to investigate erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in diagnosing pedal osteomyelitis (OM) in patients with and without diabetes, and with and without severe renal impairment (SRI). This was a retrospective cohort study of patients with moderate and severe foot infections. We evaluated three groups: Subjects without diabetes (NDM), subjects with diabetes and without severe renal insufficiency (DM-NSRI), and patients with diabetes and SRI (DM-SRI). SRI was defined as eGFR <30. We evaluated area under the curve (AUC), cutoff point, sensitivity and specificity to characterize the accuracy of ESR and CRP to diagnose OM. A total of 408 patients were included in the analysis. ROC analysis in the NDM group revealed the AUC for ESR was 0.62, with a cutoff value of 46 mm/h (sensitivity, 49.0%; specificity, 76.0%). DM-NSRI subjects showed the AUC for ESR was 0.70 with the cutoff value of 61 mm/h (sensitivity, 68.9%; specificity 61.8%). In DM-SRI, the AUC for ESR was 0.67, with a cutoff value of 119 mm/h (sensitivity, 46.4%; specificity, 82.40%). In the NDM group, the AUC for CRP was 0.55, with a cutoff value of 6.4 mg/dL (sensitivity, 31.3%; specificity, 84.0%). For DM-NSRI, the AUC for CRP was 0.70, with a cutoff value of 8 mg/dL (sensitivity, 49.2%; specificity, 80.6%). In DM-SRI, the AUC for CRP was 0.62, with a cutoff value of 7 mg/dL (sensitivity, 57.1%; specificity, 67.7%). While CRP demonstrated relatively consistent utility, ESR's diagnostic cutoff points diverged significantly. These results highlight the necessity of considering patient-specific factors when interpreting ESR results in the context of OM diagnosis.
We evaluated the primary application of crushed prednisolone combined with hydrocolloid powder for clinically diagnosed peristomal pyoderma gangrenosum (PPG). We present our data on this cohort and follow-up of our previous patients. Of the 23 patients who were commenced on this regime, 18 healed (78%). Twenty-two patients commenced on this regime as the primary treatment for their PPG, and for one, it was a rescue remedy after failed conventional therapy. Four patients with significant medical comorbidities failed to heal and one had their stomal reversal surgery before being fully healed. The proposed treatment regime for PPG is demonstrated to be effective, inexpensive and able to be managed in the patient's usual home environment. In vitro drug release analysis was undertaken, and data are presented to provide further insights into the efficacy of this regime.
Between 2013 and 2018, there has been a 71% increase in the number of patients who have required wound care in the NHS and such large numbers has placed a significant burden on healthcare systems. However, there is currently no evidence as to whether medical students are equipped with the necessary skills to deal with an increasing number of wound care related issues that patients present with. A total of 323 medical students across 18 UK medical schools completed an anonymous questionnaire evaluating the wound education received at their medical school, encompassing the volume, content, format and efficacy of teaching. 68.4% (221/323) of respondents had received some form of wound education during their undergraduate studies. On average students received 2.25 h of structured, preclinical teaching and only 1 h of clinical based teaching in total. All students that received wound education reported undertaking teaching on the physiology of, and factors affecting wound healing, with only 32.2% (n = 104) of students receiving clinically based wound education There was very weak correlation and no significant association in student's ability to assess wounds (R 2 = 0.190, p = 0.013), manage wounds (R 2 = 0.060, p = 0.37), and prescribe wound care products (R 2 = 0.093, p = 0.18) with their stage of training. Students strongly agreed that wound education is an important part of the undergraduate curriculum and post graduate practice, and do not feel their learning needs have been met. This is the first study to assess the provision of wound education in the United Kingdom, demonstrating a clear deficit in the provision of wound education compared to expectation of junior doctors. Wound education is largely overlooked in the medical curriculum, lacks a clinical focus and does not prepare junior doctors with the necessary clinical abilities to deal with wound related pathology. Expert opinion to direct changes to future curriculum and further evaluation of teaching methodology is required to address this deficit and ensure students have the necessary clinical skills to excel as newly graduated doctors.
FreshRSS 