Effectiveness of electronic quality improvement activities to reduce cardiovascular disease risk in people with chronic kidney disease in general practice: A cluster randomised trial with active control (Preprint)

BACKGROUND: Future Health Today (FHT) is a program integrated with electronic medical record (EMR) systems in general practice and comprises (1) a practice dashboard to identify people at risk of, or with, chronic disease who may benefit from intervention; (2) active clinical decision support (CDS) at the point of care; and (3) quality improvement activities. One module within FHT aims to facilitate cardiovascular disease (CVD) risk reduction in people with chronic kidney disease (CKD) through the recommendation of angiotensin-converting enzyme inhibitor inhibitors (ACEI), angiotensin receptor blockers (ARB), or statins according to Australian guidelines (defined as appropriate pharmacological therapy). OBJECTIVE: This study aimed to determine if the FHT program increases the proportion of general practice patients with CKD receiving appropriate pharmacological therapy (statins alone, ACEI or ARB alone, or both) to reduce CVD risk at 12 months postrandomization compared with active control (primary outcome). METHODS: General practices recruited through practice-based research networks in Victoria and Tasmania were randomly allocated 1:1 to the FHT CKD module or active control. The intervention was delivered to practices between October 4, 2021, and September 30, 2022. Data extracted from EMRs for eligible patients identified at baseline were used to evaluate the trial outcomes at the completion of the intervention period. The primary analysis used an intention-to-treat approach. The intervention effect for the primary outcome was estimated with a marginal logistic model using generalized estimating equations with robust SE. RESULTS: Overall, of the 734 eligible patients from 19 intervention practices and 715 from 21 control practices, 82 (11.2%) and 70 (9.8%), respectively, had received appropriate pharmacological therapy (statins alone, ACEI or ARB alone, or both) at 12 months postintervention to reduce CVD risk, with an estimated between-trial group difference (Diff) of 2.0% (95% CI -1.6% to 5.7%) and odds ratio of 1.24 (95% CI 0.85 to 1.81; P=.26). Of the 470 intervention patients and 425 control patients that received a recommendation for statins, 61 (13%) and 38 (9%) were prescribed statins at follow-up (Diff 4.3%, 95% CI 0 to 8.6%; odds ratio 1.55, 95% CI 1.02 to 2.35; P=.04). There was no statistical evidence to support between-group differences in other secondary outcomes and general practice health care use. CONCLUSIONS: FHT harnesses the data stored within EMRs to translate guidelines into practice through quality improvement activities and active clinical decision support. In this instance, it did not result in a difference in prescribing or clinical outcomes except for small changes in statin prescribing. This may relate to COVID-19-related disruptions, technical implementation challenges, and recruiting higher performing practices to the trial. A separate process evaluation will further explore factors impacting implementation and engagement with FHT. TRIAL REGISTRATION: ACTRN12620000993998; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380119

Reducing inequalities through greater diversity in clinical trials – As important for medical devices as for drugs and therapeutics

In medicine and public health, the randomised controlled trial (RCT) is generally considered the key generator of 'gold standard' evidence. However, basic and clinical research and trials are often unrepresentative of real-world populations. Recruiting insufficiently diverse cohorts of participants in trials (e.g. in terms of socioeconomic status, racial and ethnic background, or sex and gender) may not only overstate the general effectiveness of a technology; it may also actively increase health inequalities. We highlight some general issues in this domain, before discussing several specific illustrative examples in the context of medical devices. High quality evidence on factors that would improve trial recruitment is extremely limited. There is a clear need for research on candidate strategies for improving recruitment of under-represented groups in RCTs. These could include, for example, offering various forms of financial incentives; non-monetary incentives, such as preferential access to the technologies that are being tested if they are found to be effective; and various types of informational messages and nudges; as well as involvement of community partners and champions in the recruitment process. Ideally, recruitment practices should ultimately be based on evidence generated from RCTs. Studies Within a Trial (SWAT), where randomised experiments are built into the actual recruitment processes in RCTs, are an ideal way to gain this evidence. SWAT studies are seeing an increase in traction, as indicated by funding streams in bodies such as the UK-based NIHR. Making greater funding available for studies of this kind is needed to improve the evidence base on how best to improve diversity in trial recruitment

The Impact of Age on Preferences for Colorectal Cancer Surveillance Strategies: Are Fecal Immunochemical Tests FIT for Surveillance?

Introduction: Individuals with a known risk of colorectal cancer (CRC) are recommended regular surveillance colonoscopies. Alternative surveillance strategies incorporating fecal immunochemical tests (FIT) may improve colonoscopy resource utilization and be more appropriate for those with a lower risk of CRC, particularly younger adults. This study compared younger (< 50 years) and older (≥ 50 years) adults' preferences for different CRC surveillance strategies. Methods: Eight hundred individuals enrolled in a colonoscopy-based surveillance program were invited to complete a survey assessing CRC surveillance preferences. Preferences for colonoscopy frequency and the acceptability of two alternative protocols were assessed: (1) providing FIT between colonoscopies, and (2) a FIT-only strategy where colonoscopy would only be required after a positive FIT result. Results: A total of 102 younger (median age 41.4 years, 67.6% female) and 187 older (median age 68.5 years, 49.2% female) adults completed the survey. Surveillance preferences did not significantly vary by age group; most respondents preferred colonoscopies more often than their current frequency (< 50 years: 54.1%; ≥ 50 years: 58.1%). Although most participants (< 50 years: 91.2%; ≥ 50 years: 93.0%) agreed that FIT is important to complete between surveillance colonoscopies, only a small proportion were comfortable with FIT-only surveillance replacing colonoscopies (< 50 years: 27.5%; ≥ 50 years: 37.4%). Fear of CRC was a significant predictor of preferences for more frequent surveillance incorporating FIT in younger, but not older, adults. Conclusion: Many individuals with an elevated risk of CRC wanted more frequent surveillance, regardless of their age. Extending surveillance colonoscopy intervals using FIT may be a more acceptable method of reducing colonoscopy frequency rather than utilizing a FIT-only approach. Trial Registration: This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN #12619001743156)

Safety and effectiveness of the first balloon-in-basket pulsed field ablation system for the treatment of atrial fibrillation: VOLT CE Mark Study 6-month results

Aims Pulsed field ablation (PFA) is a growing ablation modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients. This study assesses the 6-month safety and effectiveness of a novel balloon-in-basket, mapping-integrated PFA system, with a purpose-built form factor for PVI. Methods and results The VOLT CE Mark Study is a prospective, multi-center, pre-market study. A total of 150 patients with drug-refractory paroxysmal (PAF) or persistent AF (PersAF) were enrolled between 8 November 2023 and 14 March 2024, of which 146 patients (age 64.1 ± 10.0 years, 63.0% male, 70.5% PAF) underwent PVI with the balloon-in-basket PFA catheter and system featuring integrated electroanatomic mapping with contact-sensing. Study endpoints were the rate of primary serious adverse events within 7 days as well as acute procedural effectiveness and 6-month freedom from recurrence. Acute effectiveness was achieved in 99.1% (573/578) of treated PVs (98.6% of patients, 144/146) with 17.6 ± 5.7 PFA applications/patient. Procedure, fluoroscopy, LA dwell, and transpired ablation times were 100.4 ± 33.0, 17.3 ± 12.1, 39.4 ± 20.6, and 31.4 ± 16.8 min, respectively. There were 4 (2.7%; 4/146) primary serious adverse events. The rate of freedom from documented atrial arrhythmias was 88.2% in PAF patients and 76.7% in PersAF patients (freedom from symptomatic recurrence was documented in 90.2% of PAF patients and 74.4% of PersAF patients) through 6-months post-index procedure. Conclusion The VOLT CE Mark Study primary results demonstrate the safety and effectiveness of the novel balloon-in-basket PFA system to perform PVI in PAF and PersAF

The Physicochemical and Rheological Properties of Green Banana Flour–Wheat Flour Bread Substitutions

Functional foods are currently receiving increasing popularity in diet modification. Green bananas contain far more dietary fiber (DF) and resistant starch (RS) than mature bananas. The potential for integrating these vital components into food, such as bread, has expanded. Thus, this study aimed to examine the physicochemical and rheological behavior of wheat flour dough after the addition of varying amounts of Australian, green banana flour (GBF) substitutions (5, 10, 15, 25, and 30%). Using MixoLab 2, we recorded the rheological parameters of the dough that had GBF substitutions. Additionally, the flour color ('L*', 'a*', and 'b*' value) and crumb cell structure analysis were evaluated. Although increasing the amount of GBF replacement generally improved dough quality with all banana cultivars, GBF from Cavendish and Ladyfinger showed a greater improvement than Ducasse. Improved dough mixing stability and increased viscosity, starch gelatinization, and retrogradation were all predicted to contribute to longer bread shelf life. RS content of the enriched bread increased significantly with both Ladyfinger and Ducasse (2.6%), while Ladyfinger bread had the highest DF (9.1%). With increasing GBF, L*, a*, and b* values were changed considerably with a strong linear correlation. A MATLAB analysis indicated substantial variations across samples regarding the small, medium, and total air space counts based on 10% banana flour as a standard level of addition. In conclusion, the processing properties and nutritional value of wheat flour can be enhanced by replacing specific proportions of wheat flour with green banana flour without major detrimental effects on dough processing attributes and thus highlight the possibility of utilizing GBF from different banana varieties for use in fine-tuning composite flour developments

Radiation protection considerations with [89Zr]Zr-girentuximab PET and surgery

BACKGROUND: 89Zr is emerging as a popular positron-emitting radionuclide for imaging; however, its 909 keV gamma emission presents shielding challenges, and radiation exposure safety guidelines for healthcare professionals working with the radionuclide have not been well-established. To guide assessment of the radiation risk and necessary safety guidelines, we present laboratory dose rate measurements of 89Zr syringes and vials, and dose rates measurements made during the ZIRCON clinical trial ([89Zr]Zr-girentuximab) to evaluate healthcare provider exposure during administration, imaging, and surgical procedures. RESULTS: The maximum dose rate from a vial with no shielding was 0.334 µSv/h/MBq, and the minimum dose rate with 66 mm lead shielding was 0.004 µSv/h/MBq. The controlled spill measured 0.52 µSv/h/MBq. Dose rates 1 m from patients who received [89Zr]Zr-girentuximab had an average of 3.90 µSv/h at imaging. During surgery, waste measured below background levels, and a bed assistant 0.8 m from the patient received a 5 µSv/h whole-body dose rate. The excised kidney measured 6 µSv/h at 5 cm. CONCLUSIONS: Our results demonstrate low radiation exposure levels associated with 89Zr handling and exposure to the patient. With potential integration of 89Zr into clinical practice, appropriate radiation safety guidelines are needed. Dose rate measurements can help guide development of best practices and site-specific protocols. CLINICAL TRIAL NUMBER: not applicable for this study; ZIRCON trial number NCT03849118, registered on 19 February 2019

Understanding Australia’s teacher shortage: the importance of psychosocial working conditions to turnover intentions

Australian policymakers are currently attempting to address an ‘unprecedented teacher shortage’. Through a survey of 905 teachers in Australian government schools, this paper examines some of the key factors influencing the career intentions of teachers in Australian government schools. Drawing upon the concept of the psychosocial work environment from the field of occupational health, this analysis examines the relationship between key workplace demands, workplace resources, teachers’ experiences and attitudes towards work, teachers’ mental health outcomes, and their intentions to either remain in or leave their roles. The results reveal significant relationships between teachers’ intentions to leave their roles and challenging working conditions, adverse work experiences, as well as heightened levels of stress, burnout, and depressive symptoms. In contrast, remaining in their role was associated with factors indicative of a supportive psychosocial work environment, such as job recognition, trust in management, organisational justice, positive work experiences, and lower levels of mental health difficulties. The study underscores the urgent need to understand and assess the psychosocial work environments of teachers, and for multi-level strategies that address both protective and risk factors

Mitochondrial damage in muscle specific PolG mutant mice activates the integrated stress response and disrupts the mitochondrial folate cycle

During mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses to preserve cellular health. One such pathway is the mitochondrial integrated stress response (mtISR), which is known to be activated by mitochondrial DNA (mtDNA) damage. However, the causal molecular signals responsible for activation of the mtISR remain mostly unknown. A gene often associated with mtDNA mutations/deletions is Polg1, which encodes the mitochondrial DNA Polymerase γ (PolG). Here, we describe an inducible, tissue specific model of PolG mutation, which in muscle specific animals leads to rapid development of mitochondrial dysfunction and muscular degeneration in male animals from ~5 months of age. Detailed molecular profiling demonstrated robust activation of the mtISR in muscles from these animals. This was accompanied by striking alterations to enzymes in the mitochondrial folate cycle that was likely driven by a specific depletion in the folate cycle metabolite 5,10 methenyl-THF, strongly implying imbalanced folate intermediates as a previously unrecognised pathology linking the mtISR and mitochondrial disease

Exploration of urban-rural disparities in institutional delivery in Bangladesh: Assessing the effect of antenatal care dynamics

Background: Improving access to institutional delivery is crucial for reducing maternal and newborn mortality. However, government efforts to enhance maternal healthcare in low- and middle-income countries (LMICs) like Bangladesh mostly contribute to a significant increase in antenatal care (ANC) uptake, while institutional delivery rates remains low, with notable urban-rural differences. We, therefore, explored the association of the place, timing, and quality of ANC with the uptake of institutional delivery services, as well as explored the urban-rural differences in these associations. Methods: The study analysed data of 3,549 mothers, extracted from the 2022 Bangladesh Demographic and Health Survey (BDHS). The outcome variable was the utilisation of institutional delivery (yes, no). The timing, location and quality of ANC were considered as the key exposure variables. A multilevel mixed-effects Poisson regression model was employed to explore associations between the outcome and the exposures. Additionally, an urban–rural differential analysis was conducted to assess the urban-rural differences in the association between exposure and outcome variables. Results: We observed a noticeable difference in institutional delivery rates between urban (76.3%) and rural areas (60.5%), with an overall rate of 64.7%. Women who accessed ANC in the 2nd or 3rd trimester were less likely to have an institutional delivery (aPR: 0.92 and 0.74) compared to those who initiated ANC in the 1st trimester. Receiving ANC at home significantly decreased the likelihood of institutional delivery (aPR: 0.74), while ANC from private or public facilities showed no significant association. Additionally, having at least one ANC visit from a medically trained provider (MTP) significantly increased the likelihood of institutional delivery (aPR: 1.83). Receiving quality ANC services also found increasing the likelihood of institutional delivery (aPR: 1.21), with these effects being more pronounced among rural women. The urban-rural differential analysis revealed no significant variation in the determinants of institutional delivery, except for the timing of ANC initiation. Conclusion: Urban-rural differences in institutional delivery rates are evident, with early ANC initiation, home-based ANC, and visits with MTPs being associated with higher institutional delivery rates. Initiation of ANC was the only determinant showing significant urban-rural variation, with notable differences in effect size for all other determinants. Therefore, to increase institutional delivery rates, particularly in rural areas, focusing on early initiation of ANC visits is important. In addition, improving the access to quality ANC services in the rural healthcare facilities is particularly crucial to increase the institutional delivery rates