Discretion in decision to receive COVID-19 vaccines and associated socio-economic inequalities in rates of uptake: a whole-of-population data linkage study from Australia.

OBJECTIVE: In Australia, first and second compared to third dose of a COVID-19 vaccine were implemented under different policies and contexts, resulting in greater discretion in decisions to receive a third compared to first and second dose. We quantified socio-economic inequalities in first and third dose to understand how discretion is associated with differences in uptake. STUDY DESIGN: Whole-of-population cohort study. METHODS: Linked immunisation, census, death and migration data were used to estimate weekly proportions who received first and third doses of a COVID-19 vaccine until 31 August 2022 for those with low (no formal qualification) compared to high (university degree) education, stratified by 10-year age group (from 30 to 89 years). We estimated relative rates using Cox regression, including adjustment for sociodemographic factors. RESULTS: Among 13.1 million people in our study population, 94% had received a first and 80% a third dose by 31 August 2022. Rates of uptake of first and third dose were around 50% lower for people with low compared to high education. Gaps were small in absolute terms for first dose, and at the end of the study period ranged from 1 to 11 percentage points across age groups. However, gaps were substantial for third dose, particularly at younger ages where the socio-economic gap was as wide as 32 percentage-points. CONCLUSION: Education-related inequalities in uptake were larger where discretion in decisions was larger. Policies that limited discretion in decisions to receive vaccines may have contributed to achieving the dual aims of maximising uptake and minimising inequalities.

SyncMRT: a solution to image-guided synchrotron radiotherapy for quality assurance and pre-clinical trials.

In this work, a new image guidance system and protocols for delivering image-guided radiotherapy (IGRT) on the Imaging and Medical Beamline (IMBL) at the ANSTO Australian Synchrotron are introduced. The image guidance methods used and the resulting accuracy of tumour alignment in in vivo experiments are often under-reported. Image guidance tasks are often complex, time-consuming and prone to errors. If unchecked, they may result in potential mis-treatments. We introduce SyncMRT, a software package that provides a simple, image guidance tool-kit for aligning samples to the synchrotron beam. We have demonstrated sub-millimetre alignment using SyncMRT and the small-animal irradiation platform (the DynamicMRT system) on the IMBL. SyncMRT has become the standard for carrying out IGRT treatments on the IMBL and has been used in all pre-clinical radiotherapy experiments since 2017. Further, we introduce two quality assurance (QA) protocols to synchrotron radiotherapy on the IMBL: the Winston-Lutz test and hidden target test. It is shown that the presented QA tests are appropriate for picking up geometrical setup errors and assessing the end-to-end accuracy of the image guidance process. Together, these tools make image guidance easier and provide a mechanism for reporting the geometric accuracy of synchrotron-based IGRT treatments. Importantly, this work is scalable to other delivery systems, and is in continual development to support the upcoming veterinary radiotherapy trials on the IMBL.

Inequalities in life expectancy in Australia according to education level: a whole-of-population record linkage study.

BACKGROUND: Life expectancy in Australia is amongst the highest globally, but national estimates mask within-country inequalities. To monitor socioeconomic inequalities in health, many high-income countries routinely report life expectancy by education level. However in Australia, education-related gaps in life expectancy are not routinely reported because, until recently, the data required to produce these estimates have not been available. Using newly linked, whole-of-population data, we estimated education-related inequalities in adult life expectancy in Australia. METHODS: Using data from 2016 Australian Census linked to 2016-17 Death Registrations, we estimated age-sex-education-specific mortality rates and used standard life table methodology to calculate life expectancy. For men and women separately, we estimated absolute (in years) and relative (ratios) differences in life expectancy at ages 25, 45, 65 and 85 years according to education level (measured in five categories, from university qualification [highest] to no formal qualifications [lowest]). RESULTS: Data came from 14,565,910 Australian residents aged 25 years and older. At each age, those with lower levels of education had lower life expectancies. For men, the gap (highest vs. lowest level of education) was 9.1 (95 %CI: 8.8, 9.4) years at age 25, 7.3 (7.1, 7.5) years at age 45, 4.9 (4.7, 5.1) years at age 65 and 1.9 (1.8, 2.1) years at age 85. For women, the gap was 5.5 (5.1, 5.9) years at age 25, 4.7 (4.4, 5.0) years at age 45, 3.3 (3.1, 3.5) years at 65 and 1.6 (1.4, 1.8) years at age 85. Relative differences (comparing highest education level with each of the other levels) were larger for men than women and increased with age, but overall, revealed a 10-25 % reduction in life expectancy for those with the lowest compared to the highest education level. CONCLUSIONS: Education-related inequalities in life expectancy from age 25 years in Australia are substantial, particularly for men. Those with the lowest education level have a life expectancy equivalent to the national average 15-20 years ago. These vast gaps indicate large potential for further gains in life expectancy at the national level and continuing opportunities to improve health equity.

Searching for the Optimal Treatment for Metallo- and Serine-ß-Lactamase Producing Enterobacteriaceae: Aztreonam in Combination with Ceftazidime-avibactam or Meropenem-vaborbactam.

Objective: Metallo-ß-lactamase (MBL)-producing Enterobacteriaceae, particularly those that co-harbor serine ß-lactamases, are a serious emerging public health threat given their rapid dissemination and the limited number of treatment options. Pre-clinical and anecdotal clinical data support the use of aztreonam in combination with ceftazidime-avibactam against these pathogens, but other aztreonam-based combinations have not been explored. The objective of this study was to evaluate the in vitro activity and compare synergy between aztreonam in combination with ceftazidime-avibactam and meropenem-vaborbactam against serine and MBL-producing Enterobacteriaceae via time-kill analyses. Methods: 8 clinical Enterobacteriaceae strains (4 Escherichia coli and 4 Klebsiella pneumoniae) co-producing NDM and at least one serine ß-lactamase were used for all experiments. Drugs were tested alone, in dual ß-lactam combinations, and in triple drug combinations against all strains. Results: All strains were resistant to ceftazidime-avibactam and meropenem-vaborbactam and 7/8 (87.5%) strains were resistant to aztreonam. Aztreonam combined with ceftazidime-avibactam was synergistic against all 7 aztreonam-resistant strains. Aztreonam combined with meropenem-vaborbactam was synergistic against all aztreonam-resistant strains with the exception of an OXA-232-producing K. pneumoniae strain. Neither triple combination was synergistic against the aztreonam-susceptible strain. Likewise, neither dual ß-lactam combination was synergistic against any strain. Conclusions: These data suggest that aztreonam plus meropenem-vaborbactam has similar activity to aztreonam plus ceftazidime-avibactam against Enterobacteriaceae producing NDM and other non-OXA-48-like serine ß-lactamases. Confirmation of these findings in future in vitro and in vivo models is warranted.

Pharmacokinetics and Dialytic Clearance of Isavuconazole During In Vitro and In Vivo Continuous Renal Replacement Therapy.

The pharmacokinetics (PK) and dialytic clearance of isavuconazole in vitro and in 7 solid organ transplant patients undergoing continuous renal replacement therapy (CRRT) were evaluated. In vivo, mean (± SD) plasma PK parameters of isavuconazole were: C max 4.00±1.45 mg/L, C min 1.76±0.76 mg/L, t ½ 48.36±29.78 h, Vss 288.78±182.11 L, CLss 4.85±3.79 L/h, and AUC 54.01±20.98 mg ⋅ h/L. Transmembrane clearance represented just 0.7% of the total isavuconazole clearance. These data suggest that isavuconazole is not readily removed by CRRT and no dose adjustments are necessary.

Text-message responsiveness to blood glucose monitoring reminders is associated with HbA1c benefit in teenagers with Type 1 diabetes.

AIMS: To evaluate an 18-month text-messaging intervention in teenagers with Type 1 diabetes and to assess factors associated with text responsiveness and glycaemic benefit. METHODS: Teenagers with diabetes (N = 147), aged 13-17 years, received two-way text reminders at self-selected times to check blood glucose levels and reply with blood glucose results. RESULTS: At baseline, the participants (48% boys, 78% white, 63% pump-treated) had a mean ± sd age of 14.9 ± 1.3 years, diabetes duration of 7.1 ± 3.9 years and HbA1c concentration of 69 ± 12 mmol/mol (8.5 ± 1.1%). The mean proportion of days with ≥1 blood glucose response declined over time (0-6 months, 60 ± 26% of days, 7-12 months, 53 ± 31% of days, 13-18 months, 43 ± 33% of days). Over 18 months, 49% responded with ≥1 blood glucose result on ≥50% of days (high responders). Regression analysis controlling for baseline HbA1c revealed no significant change in HbA1c from baseline to 18 months in high responders (P = 0.54) compared with a significant HbA1c increase in low responders (+0.3%, P = 0.01). In participants with baseline HbA1c ≥64 mmol/mol (≥8%), high responders were 2.5 times more likely than low responders to have a clinically significant [≥5.5 mmol/mol (≥0.5%)] HbA1c decrease over 18 months (P < 0.05). In participants with baseline HbA1c <64 mmol/mol(<8%), high responders were 5.7 times more likely than low responders to have an 18-month HbA1c <58 mmol/mol (<7.5%; P < 0.05). CONCLUSIONS: Teenagers with Type 1 diabetes who responded to text reminders on ≥50% of days over 18 months experienced clinically significant glycaemic benefit. There remains a need to tailor interventions to maintain teenager engagement and optimize improvements.

Validation of a contemporary adherence measure for children with Type 1 diabetes: the Diabetes Management Questionnaire.

AIMS: To evaluate the psychometric properties of the Diabetes Management Questionnaire, a brief, self-report measure of adherence to contemporary diabetes management for young people with Type 1 diabetes and their caregivers. METHODS: A total of 273 parent-child dyads completed parallel versions of the Diabetes Management Questionnaire. Eligible children (aged 8-18 years) had Type 1 diabetes for ≥1 year. A multidisciplinary team designed the Diabetes Management Questionnaire as a brief, self-administered measure of adherence to Type 1 diabetes management over the preceding month; higher scores reflect greater adherence. Psychometrics were evaluated for the entire sample and according to age of the child. RESULTS: The children (49% female) had a mean ± sd (range) age 13.3 ± 2.9 (8-18) years and their mean ± sd HbA1c was 71 ± 15 mmol/mol (8.6 ± 1.4%). Internal consistency was good for parents (α = 0.83) and children (α = 0.79). Test-retest reliability was excellent for parents (intraclass correlation coefficient =0.83) and good for children (intraclass correlation coefficient = 0.65). Parent and child scores had moderate agreement (intraclass correlation coefficient = 0.54). Diabetes Management Questionnaire scores were inversely associated with HbA1c (parents: r = -0.41, P < 0.0001; children: r = -0.27, P < 0.0001). Psychometrics were stronger in the children aged ≥13 years compared with those aged < 13 years, but were acceptable in both age groups. Mean ± sd Diabetes Management Questionnaire scores were higher among children who were receiving insulin pump therapy (n = 181) than in children receiving multiple daily injections (n = 92) according to parent (75.9 ± 11.8 vs. 70.5 ± 15.5; P = 0.004) and child report (72.2 ± 12.1 vs. 67.6 ± 13.9; P = 0.006). CONCLUSIONS: The Diabetes Management Questionnaire is a brief, valid self-report measure of adherence to contemporary diabetes self-management for people aged 8-18 years who are receiving either multiple daily injections or insulin pump therapy.

People with chronic facial pain perform worse than controls at a facial emotion recognition task, but it is not all about the emotion.

Alexithymia, or a lack of emotional awareness, is prevalent in some chronic pain conditions and has been linked to poor recognition of others' emotions. Recognising others' emotions from their facial expression involves both emotional and motor processing, but the possible contribution of motor disruption has not been considered. It is possible that poor performance on emotional recognition tasks could reflect problems with emotional processing, motor processing or both. We hypothesised that people with chronic facial pain would be less accurate in recognising others' emotions from facial expressions, would be less accurate in a motor imagery task involving the face, and that performance on both tasks would be positively related. A convenience sample of 19 people (15 females) with chronic facial pain and 19 gender-matched controls participated. They undertook two tasks; in the first task, they identified the facial emotion presented in a photograph. In the second, they identified whether the person in the image had a facial feature pointed towards their left or right side, a well-recognised paradigm to induce implicit motor imagery. People with chronic facial pain performed worse than controls at both tasks (Facially Expressed Emotion Labelling (FEEL) task P < 0·001; left/right judgment task P < 0·001). Participants who were more accurate at one task were also more accurate at the other, regardless of group (P < 0·001, r(2)  = 0·523). Participants with chronic facial pain were worse than controls at both the FEEL emotion recognition task and the left/right facial expression task and performance covaried within participants. We propose that disrupted motor processing may underpin or at least contribute to the difficulty that facial pain patients have in emotion recognition and that further research that tests this proposal is warranted.

Clustering analysis of water distribution systems: identifying critical components and community impacts.

Large water distribution systems (WDSs) are networks with both topological and behavioural complexity. Thereby, it is usually difficult to identify the key features of the properties of the system, and subsequently all the critical components within the system for a given purpose of design or control. One way is, however, to more explicitly visualize the network structure and interactions between components by dividing a WDS into a number of clusters (subsystems). Accordingly, this paper introduces a clustering strategy that decomposes WDSs into clusters with stronger internal connections than external connections. The detected cluster layout is very similar to the community structure of the served urban area. As WDSs may expand along with urban development in a community-by-community manner, the correspondingly formed distribution clusters may reveal some crucial configurations of WDSs. For verification, the method is applied to identify all the critical links during firefighting for the vulnerability analysis of a real-world WDS. Moreover, both the most critical pipes and clusters are addressed, given the consequences of pipe failure. Compared with the enumeration method, the method used in this study identifies the same group of the most critical components, and provides similar criticality prioritizations of them in a more computationally efficient time.

The impact of blood glucose and HbA(1c) goals on glycaemic control in children and adolescents with Type 1 diabetes.

AIMS: To evaluate parents' goals and parents' perceptions of physicians' goals for blood glucose and HbA(1c) in children and adolescents with Type 1 diabetes. METHODS: In a cross-sectional observational assessment, parents (80% mothers) of 153 children/adolescents (56% female), aged 12.9 ± 2.3 years (range 8-16 years) with Type 1 diabetes for 6.3 ± 3.5 years, completed surveys regarding their goals and their perceptions of physicians' goals for their child's blood glucose and HbA(1c) levels. RESULTS: Children/adolescents had a mean HbA(1c) of 69 ± 16 mmol/mol (8.4 ± 1.4%) and checked blood glucose levels 3.8 ± 1.2 times/day; 23% received pump therapy. Almost half of parents reported a blood glucose goal of 130 (80-180) mg/dl [7.2 (4.4-10) mmol/l]; 75% of parents reported a HbA(1c) goal of 42-64 mmol/mol (6-8%). HbA(1c) was significantly lower when parents reported HbA(1c) goals ≤ 64 mmol/mol (≤ 8%) vs. > 64 mmol/mol (> 8%) [67 ± 14 mmol/mol (8.3 ± 1.2%) vs. 76 ± 20 mmol/mol (9.1 ± 1.8%), respectively, P = 0.02]. Parents' blood glucose and HbA(1c) goals were tightly linked with parents' perceptions of physicians' blood glucose and HbA(1c) goals (69% concordant, P < 0.0001; 88% concordant, P < 0.0001, respectively). CONCLUSIONS: There was a significant association between lower parent HbA(1c) goals and lower child/adolescent HbA(1c) . Further, parents appear to set glycaemic goals based upon their perceptions of physician goals. Future studies should assess the relationship between parents' perceptions of health-care providers' goals and health-care providers' actual goals and the impact of unified family/provider goal-setting on glycaemic control.

Awareness of and attitudes towards skin-cancer prevention: a survey of patients in the UK presenting to their general practice.

BACKGROUND: The rate of skin cancer in the UK continues to rise. AIM: To identify the current knowledge and awareness of and attitudes towards the avoidance of skin cancer among a variety of patient groups to aid the design of future UK sun-awareness campaigns. METHODS: Patients aged ≥ 16 years presenting to one of three general practices (two urban, one rural) in the UK during the period 1 June to 31 July 2010 were invited to complete a paper-based questionnaire collecting data on their sun-exposure behaviour, with significance assessed by the Fisher exact test. RESULTS: In total, 1000 patients (327 male, 673 female) responded. Those aged 16-30 years were significantly more likely to get sunburn than the older age groups. The understanding of ways to avoid skin cancer in 16-30-year-olds was also rated as significantly worse than that of all other age groups. Compared with the older age groups, this group was also less likely to avoid midday sun exposure (P < 0.001) or to cover up in the sun (P < 0.001). There was no significant difference in sun exposure or frequency of sunburn between those with or without a personal or family history of skin cancer. Those with a positive history were more likely to wear sunscreen (P < 0.01), but not to cover up or avoid the midday sun. CONCLUSIONS: UK-based sun-awareness programmes should target younger age groups. In addition, healthcare professionals must ensure that opportunities are taken to reinforce the importance of safe sun exposure for patients presenting with skin cancer.

Effects and significance of groundwater for vegetation: A systematic review.

Groundwater represents a critical water source for plants, especially during drought, with continuous groundwater availability widely associated with the presence of ecological refugia and the preservation of biodiversity during periods of adverse conditions. Here, we present a systematic quantitative literature review of global groundwater and ecosystem interactions to synthesise current knowledge and identify key knowledge gaps and research priorities through a management lens. Despite increasing research on groundwater dependent vegetation since the late 1990s, significant geographical and ecological biases are evident with papers focused on arid regions or areas with significant anthropogenic changes. Of the 140 papers reviewed, desert and steepe arid landscapes accounted for 50.7 % and desert and xeric shrublands were represented in 37.9 % of papers. A third of papers (34.4 %) quantified groundwater uptake by ecosystems and groundwater contributions to transpiration, with studies examining the influence of groundwater on vegetation productivity, distribution, and composition also well represented. In contrast, groundwater influences on other ecosystem functions are relatively poorly explored. The research biases introduce uncertainty in the transferability of findings between locations and ecosystems limiting the generality of our current understanding. This synthesis contributes to consolidating a solid knowledge base of the hydrological and ecological interrelationships for managers, planners, and other decision-makers that is relevant to the landscapes and environments they manage, so can more effectively deliver ecological and conservation outcomes.

Re-examining a measure of diabetes-related burden in parents of young people with Type 1 diabetes: the Problem Areas in Diabetes Survey - Parent Revised version (PAID-PR).

AIMS: In a pediatric patients, the burden of diabetes lies within the family. In the current era of intensive insulin therapy, perceived parental burden may affect the family's efforts at effective diabetes management. The aims of this study were to re-examine and revise a measure of perceived parental burden associated with caring for a child with diabetes in the current era. METHODS: A geographically diverse population of young people (N = 376) with Type 1 diabetes and their parents included participants in the Juvenile Diabetes Research Foundation continuous glucose monitoring study and patients from the Joslin Diabetes Center. Participants provided data on demographics, diabetes management, diabetes-specific family conflict, and quality of life at baseline and after 6 months of follow-up. RESULTS: Young people were 12.9 ± 2.7 years old with diabetes duration of 6.3 ± 3.5 years. Mean HbA(1C) was 8.0 ± 1.2%(64 mmol/mol), 58% received insulin pump therapy, and young people monitored blood glucose 5.2 ± 2.3 times/day. Factor analysis yielded two factors, 'Immediate Burden' and 'Theoretical Burden'. The Problem Areas in Diabetes Survey - Parent Revised version (PAID-PR) demonstrated excellent internal consistency (Cronbach's α = 0.87; factor 1 α = 0.78; factor 2 α = 0.83). Greater parental burden was associated with more frequent blood glucose monitoring, higher HbA(1C) levels, greater diabetes-specific family conflict, and lower quality of life. Test-retest analysis was acceptable (r = 0.62). CONCLUSIONS: The PAID-PR demonstrated excellent internal consistency, good test-retest reliability, and associations with diabetes-specific family conflict and quality of life. This brief measure may have both clinical and research utility in the management of young people with Type 1 diabetes.

The Australian radiation protection and nuclear safety agency megavoltage photon thermoluminescence dosimetry postal audit service 2007-2010.

The Australian radiation protection and nuclear safety agency (ARPANSA) has continuously provided a level 1 mailed thermoluminescence dosimetry audit service for megavoltage photons since 2007. The purpose of the audit is to provide an independent verification of the reference dose output of a radiotherapy linear accelerator in a clinical environment. Photon beam quality measurements can also be made as part of the audit in addition to the output measurements. The results of all audits performed between 2007 and 2010 are presented. The average of all reference beam output measurements calculated as a clinically stated dose divided by an ARPANSA measured dose is 0.9993. The results of all beam quality measurements calculated as a clinically stated quality divided by an ARPANSA measured quality is 1.0087. Since 2011 the provision of all auditing services has been transferred from the Ionizing Radiation Standards section to the Australian Clinical Dosimetry Service (ACDS) which is currently housed within ARPANSA.

Australian women's perceptions and practice of sleep position in late pregnancy: An online survey.

BACKGROUND: Going-to-sleep in the supine position in later pregnancy (≥28 weeks) has been identified as a risk factor for stillbirth. Internationally, public awareness campaigns have been undertaken encouraging women to sleep on their side during late pregnancy. AIM: This study aimed to identify sleep practices, attitudes and knowledge in pregnant women, to inform an Australian safe sleeping campaign. METHODS: A web-based survey of pregnant women ≥28 weeks' gestation conducted from November 2017 to January 2018. The survey was adapted from international sleep surveys and disseminated via pregnancy websites and social media platforms. FINDINGS: Three hundred and fifty-two women participated. Five (1.6%) reported going to sleep in the supine position. Most (87.8%) had received information on the importance of side-sleeping in pregnancy. Information was received from a variety of sources including maternity care providers (186; 66.2%) and the internet (177; 63.0%). Women were more likely to report going to sleep on their side if they had received advice to do so (OR 2.3; 95% CI 1.0-5.1). Thirteen (10.8%) reported receiving unsafe advice, including changing their going-to-sleep position to the supine position. DISCUSSION: This indicates high level awareness and practice of safe late-pregnancy going-to-sleep position in participants. Opportunities remain for improvement in the information provided, and understanding needs of specific groups including Aboriginal and Torres Strait Islander women. CONCLUSION: Findings suggest Australian women understand the importance of sleeping position in late pregnancy. Inconsistencies in information provided remain and may be addressed through public awareness campaigns targeting women and their care providers.

Tendon tissue engineering: progress, challenges, and translation to the clinic.

The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products.