Abstract
Antibodies are proteins that recognize the molecular surfaces of potentially noxious molecules to mount an adaptive immune response or, in the case of autoimmune diseases, molecules that are ...part of healthy cells and tissues. Due to their binding versatility, antibodies are currently the largest class of biotherapeutics, with five monoclonal antibodies ranked in the top 10 blockbuster drugs. Computational advances in protein modelling and design can have a tangible impact on antibody-based therapeutic development. Antibody-specific computational protocols currently benefit from an increasing volume of data provided by next generation sequencing and application to related drug modalities based on traditional antibodies, such as nanobodies. Here we present a structured overview of available databases, methods and emerging trends in computational antibody analysis and contextualize them towards the engineering of candidate antibody therapeutics.
The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases has been implicated in a wide variety of cancers. Despite a high level of sequence homology in the ATP-binding site, ...the majority of reported inhibitors are selective for the FGFR1-3 isoforms and display much reduced potency toward FGFR4, an exception being the Bcr-Abl inhibitor ponatinib. Here we present the crystal structure of the FGFR4 kinase domain and show that both FGFR1 and FGFR4 kinase domains in complex with ponatinib adopt a DFG-out activation loop conformation. Comparison with the structure of FGFR1 in complex with the candidate drug AZD4547, combined with kinetic characterization of the binding of ponatinib and AZD4547 to FGFR1 and FGFR4, sheds light on the observed differences in selectivity profiles and provides a rationale for developing FGFR4-selective inhibitors.
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•The crystal structures of FGFR1 and FGFR4 bound to ponatinib are presented•FGFR1 and FGFR4 adopt the DFG-out conformation when bound to ponatinib•Structure of the phase II FGFR inhibitor AZD4547 in complex with FGFR1 is presented•Ponatinib shows slow binding kinetics compared with AZD4547
Tucker et al. report the structure of FGFR4 bound to the type II inhibitor ponatinib. Structural and biophysical comparisons with the structures of FGFR1 bound to ponatinib and the type I inhibitor AZD4547 provide insight into developing FGFR4 selective inhibitors.
The substantial public health benefits of autonomous vehicles will be optimised once all vehicles operate in autonomous mode. This form of disruptive technology will need to be widely accepted by the ...community to facilitate the regulatory and behavioural adjustments required to achieve rapid adoption. The aim of this study was to assess: i) receptiveness to autonomous vehicles; ii) the salience of various health benefits (e.g. crash prevention, emission reduction, driving stress reduction, cyclist safety, increased mobility for those unable to drive); and iii) prompted awareness of these health benefits.
Quantitative and qualitative data were generated via a national online survey of a broad range of Australians aged 16 years and over (n=1,624).
There were neutral levels of receptiveness and very low salience of health benefits, but more substantial levels of prompted awareness of positive health outcomes.
These results suggest that the public may be interested in information relating to the individual and societal health benefits of autonomous vehicles, which in turn may increase overall support for this innovation.
Australians are likely to be receptive to autonomous vehicles when provided with information relating to their public health benefits.
Background
The Acute Care for Elders (ACE) unit model of care aims to reduce common complications of hospitalization in older adults through early involvement of allied health providers, changes to ...the care environment, elder‐friendly care protocols, and proactive discharge planning.
Our hospital established a dedicated 28‐bed medical ACE unit. Because of capacity limitations, the number of eligible older medical patients often exceeds the available number of beds. Thus, some ACE unit‐eligible patients are instead admitted to other medical or surgical units for their medical care. These “bed‐spaced” ACE patients receive care by the same general internists and ACE order set that ACE unit patients are cared under. We sought to compare the health outcomes of ACE‐designated patients admitted to the ACE unit versus bed‐spaced peers cared for using a protocolized ACE order set.
Methods
3046 ACE‐designated patient admissions were analyzed (1499 ACE unit and 1547 bed‐spaced). The primary outcomes examined were discharge disposition and in‐hospital mortality. Univariate and multivariate comparisons were performed. Propensity matching was used to adjust for case mix in a post‐hoc analysis.
Results
The mean age of participants was 83.5 years for ACE unit patients and 82.6 for bedspaced patients. In adjusted models, ACE unit patients were more likely to be discharged home (OR 1.28 1.08–1.50, p = 0.003). In an unadjusted analysis, patients admitted to ACE unit were less likely to die in hospital, but this finding did not persist after adjustment for case mix.
Conclusion
Care of older adults delivered on a dedicated ACE unit increases the likelihood of discharge to home when compared to care delivered with an ACE order set alone for general internal medicine patients.
This editorial comments on an article by Palmer in this issue.
Abstract
Background
Excessive worry is an invisible disruptive force that has adverse health outcomes and may advance to other forms of disorder, such as anxiety or depression. Addressing worry and ...its influences is challenging yet crucial for informing public health policy.
Methods
We examined parents’ worries, influences, and variability before and during COVID-19 pandemic and across geography. Parents (n = 340) and their primary school-aged children from five Australian states completed an anonymous online survey in mid-2020. After literature review, we conceptualised the influences and performed a series of regression analyses.
Results
Worry levels and the variables contributing to parents’ worry varied before to during the pandemic. The proportion of parents who were "very worried all the time" increased by 14.6% in the early days of the pandemic. During the pandemic, ethnic background modified parents’ worry and parents’ history of daily distress symptoms was a significant contributor (p < 0.05). Excessive exposure to news remained significant both before and during the pandemic. The primary predictor of parents’ worry before COVID-19 was perceived neighbourhood safety, while the main predictor during COVID-19 was financial risk due to income change. Some variable such as neighbourhood safety and financial risk varied in their contribution to worry across geographical regions. The proportion of worried children was higher among distraught parents.
Conclusion
Parents’ worry during the health pandemic was not triggered by the health risks factors but by the financial risk due to income change. The study depicts inequality in the impact of COVID-19 by ethnic background. Different policies and reported virus case numbers across states may have modified the behaviour of variables contributing to the geography of parents’ worry. Exposure to stressors before the COVID-19 pandemic may have helped parents develop coping strategies during stressful events. Parents are encouraged to limit their exposure to stressful news. We advocate for parents-specific tailored policies and emphasise the need for access to appropriate mental health resources for those in need. Advancing research in geographical modelling for mental health may aid in devising much-needed location-targeted interventions and prioritising resources in future events.
In Australia, telehealth is not new, with several telehealth specialist services being available for those living in rural and remote communities. However, prior to the COVID-19 pandemic, telehealth ...was not routinely available for primary care or urban specialist appointments. There has been an increased focus in the use of telehealth within primary care, and particularly general practice, but overall, there has been limited research to date to guide telehealth best-practice based on consumer experiences and preferences within these settings. We aimed to capture the consumer experience of telehealth during the COVID-19 pandemic, through a novel Kitchen Table Discussion (KTD) method. This increases access to a broader community consumer cohort, with consumer hosts leading discussions in a safe environment. The KTDs were conducted in May 2021, with 10 community members each hosting a group of up to 10 participants. A total of 90 participants took part from across Australia, with the majority living in major cities, although a significant proportion lived in inner and outer regional areas of Australia, or had experience living in rural, regional or remote areas. Seventy percent of participants reported using telehealth in the past. Data were analysed sequentially using thematic analysis and identified key themes: modality, convenience, access, wait time, existing relationship, communication, connectivity, cost, and privacy. Overall, the future of telehealth looks hopeful from the perspective of the consumer, but significant improvements are required to improve consumer engagement and experience. It is evident that ‘one size does not fit all’, with results suggesting consumers value the availability of telehealth and having choice and flexibility to use telehealth when appropriate, but do not want to see telehealth replacing face-to-face delivery. Participants tended to agree that telehealth was not a preferred method when physical examination was required but would suit certain points of the patient journey.
One prominent barrier faced by healthcare consumers when accessing health services is a common requirement to complete repetitive, inefficient paper-based documentation at multiple registration ...sites. Digital innovation has a potential role to reduce the burden in this area, through the collection and sharing of data between healthcare providers. While there is growing evidence for digital innovations to potentially improve the effectiveness and efficiency of health systems, there is less information on the willingness of healthcare consumers to embrace and utilise technology to provide data.
The study aims to improve understanding of consumers' preference for utilising a digital health administration mobile app.
The online study used a stated preference experiment design to explore aspects of consumers' preference for a mobile health administration app and its impact on the likelihood of using the app. The survey was answered by a representative sample (by age and gender) of Australian adults, and sociodemographic factors were also recorded for analysis. Each participant answered eight choice sets in which a hypothetical app (defined by a set of dimensions and levels) was presented and the respondent was asked if they would be willing to provide data using that app. Analysis was conducted using bivariate logistic regression.
For the average respondent, the two most important dimensions were the time it took to register on the app and the electronic governance arrangements around their personal information. Willingness to use any app was found to differ based on respondent characteristics: people with higher education, and women, were relatively more willing to utilise the mobile health app.
This study investigated consumers' willingness to utilise a digital health administration mobile app. The identification of key characteristics of more acceptable apps provide valuable insight and recommendations for developers of similar digital health administration technologies. This would increase the likelihood of achieving successful acceptance and utilisation by consumers. The results from this study provide evidence-based recommendations for future research and policy development, planning and implementation of digital health administration mobile applications in Australia.
Background
The EQ-5D-5L has recently been developed to improve the sensitivity of the widely used three-level version. Valuation studies are required before the use of this new instrument can be ...adopted. The use of discrete choice experiments (DCEs) in this area is a promising area of research.
Purpose
To test the plausibility and acceptability of estimating an Australian algorithm for the newly developed five-level version of the EQ-5D using a DCE.
Methods
A choice experiment was designed, consisting of 200 choice sets blocked such that each respondent answered 10 choice sets. Each choice set presented two health state–duration combinations, and an immediate death option. The experiment was implemented in an online Australian-representative sample. A random-effects probit model was estimated. To explore the feasibility of the approach, an indicative algorithm was developed. The algorithm is transformed to a 0 to 1 scale suitable for use to estimate quality-adjusted life-year weights for use in economic evaluation.
Results
A total of 973 respondents undertook the choice experiment. Respondents were slightly younger and better educated than the general Australian population. Of the 973 respondents, 932 (95.8 %) completed all ten choice sets, and a further 12 completed some of the choice sets. In choice sets in which one health state–duration combination dominated another, the dominant option was selected on 89.5 % of occasions. The mean and median completion times were 17.9 and 9.4 min, respectively, exhibiting a highly skewed distribution. The estimation results are broadly consistent with the monotonic nature of the EQ-5D-5L. Utility is increasing in life expectancy (i.e., respondents tend to prefer health profiles with longer life expectancy), and mainly decreases in higher levels in each dimension of the instrument. A high proportion of respondents found the task clear and relatively easy to complete.
Conclusions
DCEs are a feasible approach to the estimation of utility weights for more complex multi-attribute utility instruments such as the EQ-5D-5L.
This study aims to elicit consumer preferences regarding telehealth and face-to-face consultations in Australia. It used a discrete choice experiment, presenting participants with a series of ...hypothetical choices, and based on their responses, infer what is most important to them. Data were analysed using conditional logit regression and latent class analysis. A total of 1,025 participants completed the survey, considering four different clinical scenarios. Face-to-face contacts were, on average, preferred to either telephone or video services. However, telehealth was identified as an attractive option if it prevents significant travel and can be conducted with a familiar doctor. Participants were strongly driven by cost, particularly greater than $30. Telehealth was least preferred for situations involving a new and unknown physical symptom, and relatively more preferred for surgical follow-up. The latent class analysis demonstrates only 15.9% of participants appeared unwilling to consider telehealth. The findings of this study suggest that meeting the needs of the Australian population requires a blended approach to service delivery, with telehealth being valued in a range of clinical scenarios. Price sensitivity was evident, therefore if telehealth services can be delivered with lower patient cost, then they are likely to be attractive.
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