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Background: This study evaluates primary care practices' engagement with various features of a quality improvement (QI) intervention for patients with coronary heart disease (CHD) in four Australian states., Methods: Twenty-seven practices participated in the QI intervention from November 2019 -November 2020. A combination of surveys, semi-structured interviews and other materials within the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease (QUEL) study were used in the process evaluation. Data were summarised using descriptive statistical and thematic analyses for 26 practices., Results: Sixty-four practice team members and Primary Health Networks staff provided feedback, and nine of the 63 participants participated in the interviews. Seventy-eight percent (40/54) were either general practitioners or practice managers. Although 69% of the practices self-reported improvement in their management of heart disease, engagement with the intervention varied. Forty-two percent (11/26) of the practices attended five or more learning workshops, 69% (18/26) used Plan-Do-Study-Act cycles, and the median (Interquartile intervals) visits per practice to the online SharePoint site were 170 (146-252) visits. Qualitative data identified learning workshops and monthly feedback reports as the key features of the intervention., Conclusion: Practice engagement in a multi-featured data-driven QI intervention was common, with learning workshops and monthly feedback reports identified as the most useful features. A better understanding of these features will help influence future implementation of similar interventions., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134., Competing Interests: The funding body and industry partners were not involved in the design of the study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Amgen and Sanofi Australia have provided cash support to the main study. MW is a consultant to Amgen, Freeline and Kyowa Kirin. Other authors have nothing to disclose. This does not alter our adherence to PLOS ONE policy on sharing data and materials., (Copyright: © 2024 Hafiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Conjugate vaccines produced either by chemical or biologically conjugation have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccine assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel biotechnological platform that overcomes the limitations of the current conjugate vaccine design method(s). As a model, we focused our design on a leading bioconjugation method using N-oligosaccharyltransferase (OTase), PglB. The installation of MAGIC led to at least twofold increase in glycoconjugate yield via MAGIC when compared to conventional N-OTase based bioconjugation method(s). Then, we improved MAGIC to (a) allow rapid installation of glycoengineering component(s), (b) omit the usage of antibiotics, (c) reduce the dependence on protein induction agents. Furthermore, we show the modularity of the MAGIC platform in performing glycoengineering in bacterial species that are less genetically tractable than the commonly used Escherichia coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against serious bacterial pathogens. We anticipate the utility of the MAGIC platform could enhance vaccines production due to its compatibility with virtually any bioconjugation method, thus expanding vaccine biopreparedness toolbox., (© 2023. BioMed Central Ltd., part of Springer Nature.)

As population aging progresses, demands of patients with cardiovascular diseases (CVD) on the primary care services is inevitably increased. However, the utilisation of primary care services across varying age groups is unknown. The study aims to explore age-related variations in provision of chronic disease management plans, mental health care, guideline-indicated cardiovascular medications and influenza vaccination among patients with CVD over differing ages presenting to primary care. Data for patients with CVD were extracted from 50 Australian general practices. Logistic regression, accounting for covariates and clustering effects by practices, was used for statistical analysis. Of the 14,602 patients with CVD (mean age, 72.5 years), patients aged 65-74, 75-84 and ≥85 years were significantly more likely to have a GP management plan prepared (adjusted odds ratio (aOR): 1.6, 1.88 and 1.55, respectively, p < 0.05), have a formal team care arrangement (aOR: 1.49, 1.8, 1.65, respectively, p < 0.05) and have a review of either (aOR: 1.63, 2.09, 1.93, respectively, p < 0.05) than those < 65 years. Patients aged ≥ 65 years were more likely to be prescribed blood-pressure-lowering medications and to be vaccinated for influenza. However, the adjusted odds of being prescribed lipid-lowering and antiplatelet medications and receiving mental health care were significantly lowest among patients ≥ 85 years. There are age-related variations in provision of primary care services and pharmacological therapy. GPs are targeting care plans to older people who are more likely to have long-term conditions and complex needs., Competing Interests: T.U. received research grants support from NHMRC and MRFF and received consulting fees from NPS MedicineWise. RG received NHMRC Solve-CHD Synergy Grant. N.Z. received grants from Australian National Health and Medical Research Council. KH received grants from NHMRC Investigator Grant (Emerging leadership). J.R. hold a fellowship from the NHMRC (GNT2007946). E.R.A. received grants from National Heart Foundation Australia-Vanguard Grant 2019. D.H. received research funds from Vifor and Lundbeck, and consulting fees from Pfizer, Amgen, Boehringer-Ingelheim, Novartis, Sanofi and Bayer. C.K.C. received NHMRC Investigator grant. C.H. received research grants from NHMRC, RACGP Foundation, HCF, Sanofi, Amgen, and Heart Research Institute. C.H. received consulting fees under sponsorship of Boehringer Ingelheim, Novo Nordisk, Pfizer, Amgen and PSA, and Gratuity payments for membership on GP Advisory Boards for Pfizer, Amgen, Astra, Zeneca, GSK and Novartis. M.W. is a consultant to Amgen, Freeline and Kyowa Kirin.

Background: Hypertension control remains a significant challenge in reducing the cardiovascular disease burden worldwide. Community peer-support groups have been identified as a promising strategy to improve medication adherence and blood pressure (BP) control., Objectives: The study aimed to evaluate the feasibility and impact of adherence clubs to improve BP control in Southeast Nigeria., Methods: This was a mixed-methods research involving a formative (pre-implementation) research, pilot study and process evaluation. Hypertensive patients in two communities were recruited into peer-support adherence clubs under the leadership of role-model patients to motivate and facilitate medication adherence, BP monitoring, and monthly medication delivery for six months. The primary outcome was medication adherence measured using visual analogue scale (VAS), with BP level at six months as a key secondary outcome., Results: We recruited a total of 104 participants. The mean age was 56.8 (SD-10.7) years, 72 (69.2%) were women, mean BP was 146.7 (SD-20.1)/86.9 (SD-11.2) mmHg, and the mean percentage of medication adherence on the VAS was 41.4% (SD-11.9%). At six months, 67 patients were assessed; self-reported adherence on the VAS increased to 57.3% (SD-25.3%) (mean difference between baseline and follow-up of 15.5%, p < 0.0001), while the mean BP decreased to 132.3 (SD-22.0)/82.9 (SD-12.2) mmHg (mean difference of 13.0 mmHg in systolic BP, p < 0.0001 and of 3.6 mmHg in diastolic BP, p = 0.02). Five in-depth interviews and four focus groups discussions were conducted as part of the qualitative analyses of the study. The participants saw hypertension as a big issue, with many unaware of the diagnosis, and they accepted the CLUBMEDS differential service delivery (DSD) model concept in hypertension., Conclusions: The study demonstrates that the implementation of adherence clubs for hypertension control is feasible and led to a statistically significant and clinically meaningful improvement in self-reported medication adherence, resulting in BP reduction. Upscaling the intervention may be needed to confirm these findings., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

The aim of our study was to estimate the size of regression to the mean with home blood pressure (BP) monitoring and compare with that for office BP. Office and home BP measures were obtained from the BP GUIDE (value of central Blood Pressure for GUIDing managEment for hypertension) study, in which 286 patients had BP measured every 3 months for 12 months. Patients were categorized by 10 mm Hg strata of baseline BP, and regression to the mean measures was calculated for home and office BP. High baseline home BP readings tended to be lower on long-term follow-up, and low baseline readings tended to be higher. For example, patients in the group with mean baseline home systolic BP ≥ 150 mm Hg had a mean baseline systolic BP of 156 mm Hg, which fell to 143 mm Hg at 12 months; and patients in the group with mean baseline home systolic BP < 120 mm Hg had a mean baseline systolic BP of 113 mm Hg which rose to 120 mm Hg at 12 months. Similar patterns were seen in intervention and control groups, and for diastolic BP. The regression dilution ratio for home systolic BP and diastolic BP was 0.52 and 0.64, respectively, compared to 0.40 and 0.55 for office systolic BP and diastolic BP, respectively. Home BP is subject to regression to the mean to a similar degree as office BP. These findings have implications for the diagnosis and management of hypertension using home BP., (© 2020 Wiley Periodicals LLC.)

Background: Cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, is the leading cause of death and disability globally. A large proportion of mortality occurs in people with prior CHD and effective and scalable strategies are needed to prevent associated deaths and hospitalisations. The aim of this study is to determine if a practice-level collaborative quality improvement program, focused on patients with CHD, reduces the rate of unplanned CVD hospitalisations and major adverse cardiovascular events, and increases the proportion of patients achieving risk factor targets at 24 months., Methods: Cluster randomised controlled trial (cRCT) to evaluate the effectiveness of a primary care quality improvement program in 50 primary care practices (n~ 10,000 patients) with 24-month follow-up. Eligible practices will be randomised (1:1) to participate in either the intervention (collaborative quality improvement program) or control (standard care) regimens. Outcomes will be assessed based on randomised allocation, according to intention-to-treat. The primary outcome is the proportion of patients with unplanned CVD hospitalisations at 2 years. Secondary outcomes are proportion of patients with major adverse cardiovascular events, proportion of patients who received prescriptions for guideline-recommended medicines, proportion of patients achieving national risk factor targets and proportion with a chronic disease management plan or review. Differences in the proportion of patients who are hospitalised (as well as binary secondary outcomes) will be analysed using log-binomial regression or robust Poisson regression, if necessary., Discussion: Despite extensive research with surrogate outcomes, to the authors' knowledge, this is the first randomised controlled trial to evaluate the effectiveness of a data-driven collaborative quality improvement intervention on hospitalisations, CVD events and cardiovascular risk amongst patients with CHD in the primary care setting. The use of data linkage for collection of outcomes will enable evaluation of this potentially efficient strategy for improving management of risk and outcomes for people with heart disease., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134 (dated 20th December 2019).

Background: Physical manipulation of the manufactured dose form is a common practice, with almost a quarter of all drugs administered in primary care having their dose altered. Splitting a tablet can be advantageous as it facilitates swallowing, allows for dose flexibility and provides cost reductions. However, there are concerns these physical changes can lead to inaccurate portions resulting in significant variations from the prescribed dose. Thus, the review described in this protocol aims to summarise the literature assessing the effect of tablet splitting on dose accuracy., Methods: Relevant studies will be identified through electronic searches in databases including EMBASE, MEDLINE, CINAHL, and the Cochrane Library, from the beginning of databases until January 2020. Studies investigating any drug, where the tablet was split, will be potentially eligible. Two reviewers will independently screen studies and extract data using standardised forms. Data extracted will include general study information, characteristics of the study, intervention characteristics and outcomes. Primary outcome is to assess dose accuracy of a split tablet measured by drug content or weight variability. Assessment of risk of bias will be dependent upon study design. If deemed feasible, meta-analysis will be performed., Results: The study described within this protocol will provide a synthesis of current evidence assessing the effect of tablet splitting on dose accuracy., Conclusion: The conclusion of our study will provide evidence to judge whether splitting a tablet results in an accurate half dose., Ethics and Dissemination: Ethics approval was not required for this study. The results of the systematic review described will be published in a peer-reviewed journal., Registration Details: PROSPERO CRD42018106252.

Background: M-learning is education using personal mobile electronic devices. Given the prevalence of these in society and amongst healthcare professionals, we aimed to assess their use and feasibility in improving the educational programme of a single vascular institution., Methods: A weekly vascular departmental teaching programme was initiated with registrars giving 30-min presentations on a defined book chapter. Two multiple-choice questions (MCQ) per session were devised by a supervising consultant utilising the smartphone response system application, Polltogo. A separate investigator disseminated one pre-teaching and one post-teaching MCQ to the attending trainees via a WhatsApp group. Instant feedback of the correct answer was provided by the application. Participants' satisfaction was judged through a survey after 13 sessions., Results: 11 junior doctors of varying seniority participated in the trial. The median number of session attendees was 5. 129 MCQ responses were received. The mobile engagement score (number of answers received divided by total possible answers) was 97.7%. The average correct score for pre-teaching MCQs was 39.4% and post-teaching MCQs 73.0% (p < 0.001). Satisfaction with the concept was high; 80% of responders agreed that it was a useful adjunct to the teaching programme whilst 90% found the system highly user-friendly., Conclusions: Smartphones can be utilised effectively and with high user satisfaction in assessing knowledge transfer throughout a departmental education programme. Trainees' responses to MCQs significantly improved after 30-min teaching sessions. This concept of m-learning could be developed further to assist with postgraduate examination revision or Deanery teaching programmes in larger cohorts.

Objective: Initiatives that support primary care to better enable delivery of optimal prevention services are of great importance. The purpose of this study was to examine the frequency of medical consultations by patients with acute coronary syndrome (ACS) in the 6 months after hospital discharge and to determine whether the frequency of visits was associated with differences in lifestyle, clinical measures and medication prescription., Methods: We conducted a retrospective subgroup analysis of data collected in the Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE), which is an ongoing (prospective) clinical initiative providing continuous real-time reporting on the clinical characteristics, management and outcomes of patients admitted to Australian hospitals with ACS. We compared clinical measures, medications, smoking status and receipt of cardiac rehabilitation with frequency of medical consultations 6 months after hospital discharge., Results: Patients with ACS visited their general practitioner (GP) a mean of 4.4 (± 3.8) times and their cardiologist 1.2 (± 0.9) times in the 6-month period after their index admission. Patients who saw a GP in the 6-month period had significantly higher rates of participation in cardiac rehabilitation, receipt of dietary advice and prescription of cardioprotective medications. Factors associated with increased frequency of GP visits were older age groups (oldest fourth vs youngest fourth incidence rate ratio (IRR) 1.08; 95% CI 1.01, 1.14), being female (male vs female IRR 0.83; 95% CI 0.80, 0.86), diagnosis of ST-segment elevation myocardial infarction (STEMI) (STEMI vs non-STEMI IRR 1.08; 95% CI 1.04, 1.13; STEMI vs unstable angina IRR 1.01; 95% CI 0.95, 1.06), being a current smoker (IRR 1.09; 95% CI 1.05, 1.15), history of cardiovascular disease (IRR 1.06; 95% CI 1.01, 1.12), history of diabetes (IRR 1.25; 95% CI 1.21, 1.31), inpatient revascularisation (IRR 0.95; 95% CI 0.91, 0.99), receipt of cardiac rehabilitation referral (IRR 0.93; 95% CI 0.89, 0.97), and discharged on four or more out of five indicated medications (IRR 1.04; 95% CI 1.00, 1.08)., Conclusion: The majority of ACS survivors in this study saw their GP frequently and their cardiologist at least once during the 6 months after index admission. Seizing these opportunities to engage, manage and support patients is important for strengthening prevention in primary care.

Background: Cardiovascular disease is the most frequent cause of death in Australia, with an associated cost burden of 11% of Australian annual health expenditure of which 40% is for hospital admissions. We investigated health outcomes and the components of hospital expenditure in the two years after an atherothrombotic disease admission to a tertiary hospital in an Australian setting., Methods: Using data linkage we analysed two years of hospitalisation data and death records of all men and women aged 35-84 years with an admission to a Western Australian tertiary hospital for atherothrombotic disease in 2007. Costs were identified by matching the Australian refined diagnostic related group on the admission records to the published schedules of public and private hospital costs for the period of interest, and converted to 2013 Australian dollars., Results: Of 6172 patients studied (74% coronary, 20% cerebrovascular, 6% peripheral), 783 (13%) died during follow-up and 174 of these were in hospital case-fatalities at index. Thirty-two percent of patients (n = 1965) accounted for 3172 readmissions to hospital with one in three having multiple hospitalisations. The hazard ratio of atherothrombotic disease readmission was 1.45 (95% CI 1.27, 1.66) in those with more than one vascular territory affected compared to those with only one territory affected after controlling for age, sex, comorbidity, admission type, procedures, and episode length of stay. The total index plus 2-year admission cost for atherothrombotic disease was calculated at $101 million; $71 million for index, and $30 million for readmissions., Conclusions: Among patients hospitalised with atherothrombotic disease, the cost of related rehospitalisations within 24 months is almost a third of the total. Much of the readmission costs fell within the first year. Whether readmissions and cost associated with atherothrombotic disease can be lowered through secondary prevention measures requires further investigation.

Objectives: The natural history of early-onset Alzheimer's disease (AD) and fronto-temporal dementia (FTD) remains to be described in detail. We seek to describe the natural history of early onset AD and FTD in terms of changes in cognitive assessment and staging, medical history and survival., Design: Longitudinal prospective cohort analysis., Setting: Neurodegenerative disorders research clinic., Participants: In total, 155 consecutive patients with clinically confirmed sporadic early-onset AD or FTD at a neurodegenerative disorders research clinic in Subiaco, Western Australia (The Artemis Project)., Methods: A detailed history was recorded from the patients at baseline, including education, family history and medical history. Mini-mental state exam (MMSE), Global Deterioration Scale (GDS) and total functional capacity (TFC) were determined at each visit from 1994 until 2011. Kaplan-Meier survival analysis was performed., Results: Patients with FTD were more likely to have a family history of dementia (p=0.026), to develop at least one cerebrovascular risk factor (p=0.003), manifest depression (Fisher's exact p=0.007) and to die during the follow-up period (Pearson χ(2) 8.97, p=0.003). Kaplan-Meier survival estimates revealed a highly significant difference in the proportion of patients surviving the follow-up period (log rank 7.25, p=0.007) with FTD patients experiencing poorer survival than those with AD. The mean MMSE and TFC were consistently lower in those with FTD compared with those with AD over a decade of follow-up; mean GDS was consistently higher in those with FTD over the follow-up period., Conclusions: We believe that the difference in survival in patients with AD and FTD in our cohort might relate to the development of one or more cerebrovascular risk factors in FTD patients and the severity of the underlying pathology.

Alzheimer's disease (AD) is the largest cause of dementia, affecting 35.6 million people in 2010. Amyloid precursor protein, presenilin 1 and presenilin 2 mutations are known to cause familial early-onset AD, whereas apolipoprotein E (APOE) ε4 is a susceptibility gene for late-onset AD. The genes for phosphatidylinositol-binding clathrin assembly protein, clusterin and complement receptor 1 have recently been described by genome-wide association studies as potential risk factors for late-onset AD. Also, a genome association study using single neucleotide polymorphisms has identified an association of neuronal sortilin related receptor and late-onset AD. Gene testing, and also predictive gene testing, may be of benefit in suspected familial early-onset AD however it adds little to the diagnosis of late-onset AD and does not alter the treatment. We do not recommend APOE ε4 genotyping.