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Background Challenges remain in translating the well-established evidence for management of cardiovascular disease (CVD) risk into clinical practice. Although electronic clinical decision support (CDS) systems are known to improve practitioner performance, their development in Australian primary health care settings is limited. Objectives Study aims were to (1) develop a valid CDS tool that assists Australian general practitioners (GPs) in global CVD risk management, and (2) preliminarily evaluate its acceptability to GPs as a point-of-care resource for both general and underserved populations. Methods CVD risk estimation (based on Framingham algorithms) and risk-based management advice (using recommendations from six Australian guidelines) were programmed into a software package. Tool validation: Data from 137 patients attending a physician’s clinic were analyzed to compare the tool’s risk scores with those obtained from an independently programmed algorithm in a separate statistics package. The tool’s management advice was compared with a physician’s recommendations based on a manual review of the guidelines. Field test: The tool was then tested with 21 GPs from eight general practices and three Aboriginal Medical Services. Customized CDS-based recommendations were generated for 200 routinely attending patients (33% Aboriginal) using information extracted from the health record by a research assistant. GPs reviewed these recommendations during each consultation. Changes in CVD risk factor measurement and management were recorded. In-depth interviews with GPs were conducted. Results Validation testing: The tool’s risk assessment algorithm correlated very highly with the independently programmed version in the separate statistics package (intraclass correlation coefficient 0.999). For management advice, there were only two cases of disagreement between the tool and the physician. Field test: GPs found 77% (153/200) of patient outputs easy to understand and agreed with screening and prescribing recommendations in 72% and 64% of outputs, respectively; 26% of patients had their CVD risk factor history updated; 73% had at least one CVD risk factor measured or tests ordered. For people assessed at high CVD risk (n = 82), 10% and 9%, respectively, had lipid-lowering and BP-lowering medications commenced or dose adjustments made, while 7% newly commenced anti-platelet medications. Three key qualitative findings emerged: (1) GPs found the tool enabled a systematic approach to care; (2) the tool greatly influenced CVD risk communication; (3) successful implementation into routine care would require integration with practice software, minimal data entry, regular revision with updated guidelines, and a self-auditing feature. There were no substantive differences in study findings for Aboriginal Medical Services GPs, and the tool was generally considered appropriate for use with Aboriginal patients. Conclusion A fully-integrated, self-populating, and potentially Internet-based CDS tool could contribute to improved global CVD risk management in Australian primary health care. The findings from this study will inform a large-scale trial intervention.

Optimal detection and subsequent risk stratification of people with chronic kidney disease (CKD) requires simultaneous consideration of both kidney function (glomerular filtration rate [GFR]) and kidney damage (as indicated by albuminuria or proteinuria). Measurement of urinary albuminuria and proteinuria is hindered by a lack of standardisation regarding requesting, sample collection, reporting and interpretation of tests. A multidisciplinary working group was convened with the goal of developing and promoting recommendations that achieve consensus on these issues. The working group recommended that the preferred method for assessment of albuminuria in both diabetic and non-diabetic patients is urinary albumin-to-creatinine ratio (UACR) measurement in a first-void spot urine specimen. Where a first-void specimen is not possible or practical, a random spot urine specimen for UACR is acceptable. The working group recommended that adults with one or more risk factors for CKD should be assessed using UACR and estimated GFR every 1-2 years, depending on their risk-factor profile. Recommended testing algorithms and sex-specific cut-points for microalbuminuria and macroalbuminuria are provided. The working group recommended that all pathology laboratories in Australia should implement the relevant recommendations as a vital component of an integrated national approach to detection of CKD. [ABSTRACT FROM AUTHOR]

The publication of the Australasian Creatinine Consensus Working Group's position statements in 2005 and 2007 resulted in automatic reporting of estimated glomerular filtration rate (eGFR) with requests for serum creatinine concentration in adults, facilitated the unification of units of measurement for creatinine and eGFR, and promoted the standardisation of assays. New advancements and continuing debate led the Australasian Creatinine Consensus Working Group to reconvene in 2010. The working group recommends that the method of calculating eGFR should be changed to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, and that all laboratories should report eGFR values as a precise figure to at least 90 mL/min/1.73 m(2). Age-related decision points for eGFR in adults are not recommended, as although an eGFR < 60 mL/min/1.73 m(2) is very common in older people, it is nevertheless predictive of significantly increased risks of adverse clinical outcomes, and should not be considered a normal part of ageing.If using eGFR for drug dosing, body size should be considered, in addition to referring to the approved product information. For drugs with a narrow therapeutic index, therapeutic drug monitoring or a valid marker of drug effect should be used to individualise dosing. The CKD-EPI formula has been validated as a tool to estimate GFR in some populations of non-European ancestry living in Western countries. Pending publication of validation studies, the working group also recommends that Australasian laboratories continue to automatically report eGFR in Aboriginal and Torres Strait Islander peoples. The working group concluded that routine calculation of eGFR is not recommended in children and youth, or in pregnant women. Serum creatinine concentration (preferably using an enzymatic assay for paediatric patients) should remain as the standard test for kidney function in these populations. [ABSTRACT FROM AUTHOR]

Background: The Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP) Study aims to examine whether a polypill-based strategy (using a single capsule containing aspirin, a statin and two blood pressure-lowering agents) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline-indicated therapies, and lower blood pressure and cholesterol levels.Methods/design: The study is an open, randomised, controlled, multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practices and Aboriginal Medical Services, followed for an average of 18 months. The participants will be randomised to one of two versions of the polypill, the version chosen by the treating health professional according to clinical features of the patient, or to usual care. The primary study outcomes will be changes, from baseline measures, in serum cholesterol and systolic blood pressure and self-reported current use of aspirin, a statin and at least two blood pressure lowering agents. Secondary study outcomes include cardiovascular events, renal outcomes, self-reported barriers to indicated therapy, prescription of indicated therapy, occurrence of serious adverse events and changes in quality-of-life. The trial will be supplemented by formal economic and process evaluations.Discussion: The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated.Trial Registration: This trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN126080005833347. [ABSTRACT FROM AUTHOR]

Jacinta Sheehan,1 Kate Laver,2 Anoo Bhopti,1 Miia Rahja,2 Tim Usherwood,3,4 Lindy Clemson,5 Natasha A Lannin1,6,7 1Department of Occupational Therapy, Social Work and Social Policy, School of Allied Health, La Trobe University, Melbourne, Australia; 2Department of Rehabilitation, Aged and Extended Care, Flinders University, Adelaide, Australia; 3Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; 4The George Institute for Global Health, Sydney, Australia; 5School of Health Sciences, Faculty of Medicine & Health, The University of Sydney, Sydney, Australia; 6Department of Neurosciences, Central Clinical School, Monash University, Melbourne, Australia; 7Alfred Health (Allied Health), Melbourne, AustraliaCorrespondence: Natasha A LanninDepartment of Neurosciences, Central Clinical School, Monash University, Level 6, 99 Commercial Road, Melbourne, VIC, 3004, AustraliaTel +61 3 9903 0304Email natasha.lannin@monash.eduBackground: There is a compelling rationale that effective communication between hospital allied health and primary care practitioners may improve the quality and continuity of patient care. It is not known which methods of communication to use, nor how effectively they facilitate the transition of care when a patient is discharged home from hospital. Our systematic review aims to investigate the methods and effectiveness of communication between hospital allied health and primary care practitioners.Methods: Systematic review of quantitative and qualitative studies with narrative synthesis. Medline, CINAHL, EMBASE, PsycInfo and Proquest Nursing and Allied Health Sources were searched from January 2003 until January 2020 for studies that examined hospital-based allied health professionals communicating with community-based primary care practitioners. Risk of bias in the different study designs was appraised using recognized tools and a content analysis conducted of the methodologies used.Results: From the located 12,281 papers (duplicates removed), 24 studies met the inclusion criteria with hospital allied health communicating in some form with primary care practitioners. While none of the included studies specifically investigated the methods or effectiveness of communication between hospital allied health and primary care practitioners, 12 of the 24 studies described processes that addressed components of their discharge communication. Four enablers to effective communication between hospital allied health and primary care practitioners were identified: multidisciplinary care plans, patient and caregiver involvement, health information technology and a designated person for follow up/care management.Conclusion: There is currently no “gold standard” method or measure of communication between hospital allied health and primary care practitioners. There is an urgent need to develop and evaluate multidisciplinary communication with enhanced information technologies to improve collaboration across care settings and facilitate the continuity of integrated people-centered care.Keywords: multidisciplinary, collaboration, discharge plan, continuity of care

Background: Asthma guidelines advise addressing adherence at every visit, but no simple tools exist to assist clinicians in identifying key adherence-related beliefs or behaviours for individual patients. Aims: To identify potentially modifiable beliefs and behaviours that predict electronically recorded adherence with controller therapy. Methods: Patients aged ≥14 years with doctor-diagnosed asthma who were prescribed inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) completed questionnaires on medication beliefs/behaviours, side-effects, Morisky adherence behaviour score and Asthma Control Test (ACT), and recorded spirometry. Adherence with ICS/LABA was measured electronically over 8 weeks. Predictors of adherence were identified by univariate and multivariate analyses. Results: 99/100 patients completed the study (57 female; forced expiratory volume in 1 s mean ± standard deviation 83 ± 23% predicted; ACT 19.9 ± 3.8). Mean electronically recorded adherence ( n= 85) was 75% ± 25, and mean self-reported adherence was 85% ± 26%. Factor analysis of questionnaire items significantly associated with poor adherence identified seven themes: perceived necessity, safety concerns, acceptance of asthma chronicity/medication effectiveness, advice from friends/family, motivation/routine, ease of use and satisfaction with asthma management. Morisky score was moderately associated with actual adherence ( r=−0.45, P < 0.0001). In regression analysis, 10 items independently predicted adherence (adjusted R2= 0.67; P < 0.001). Opinions of friends/family about the patient's medication use were strongly associated with poor adherence. Global concerns about ICS/LABA therapy were more predictive of poor adherence than were specific side-effects; the one-third of patients who reported experiencing side-effects from their steroid inhaler had lower adherence than others (mean 62% vs 81%; P= 0.015). Conclusions: This study identified several specific beliefs and behaviours which clinicians could use for initiating patient-centred conversations about medication adherence in asthma. [ABSTRACT FROM AUTHOR]

BACKGROUND: General practitioners (GPs) can be provided with effective training in the skills to manage depression. However, it remains uncertain whether such training achieves health gain for their patients. METHOD: The study aimed to measure the health gain from training GPs in skills for the assessment and management of depression. The study design was a cluster randomized controlled trial. GP participants were assessed for recognition of psychological disorders, attitudes to depression, prescribing patterns and experience of psychiatry and communication skills training. They were then randomized to receive training at baseline or the end of the study. Patients selected by GPs were assessed at baseline, 3 and 12 months. The primary outcome was depression status, measured by HAM-D. Secondary outcomes were psychiatric symptoms (GHQ-12) quality of life (SF-36), satisfaction with consultations, and health service use and costs. RESULTS: Thirty-eight GPs were recruited and 36 (95%) completed the study. They selected 318 patients, of whom 189 (59%) were successfully recruited. At 3 months there were no significant differences between intervention and control patients on HAM-D, GHQ-12 or SF-36. At 12 months there was a positive training effect in two domains of the SF-36, but no differences in HAM-D, GHQ-12 or health care costs. Patients reported trained GPs as somewhat better at listening and understanding but not in the other aspects of satisfaction. CONCLUSIONS: Although training programmes may improve GPs' skills in managing depression, this does not appear to translate into health gain for depressed patients or the health service. [ABSTRACT FROM AUTHOR]

Examines the validity of short form 36 health survey questionnaire (SF-36) in Sheffield, England. Comparison between the health profile of Nottingham and Sheffield; Detection of low levels ill health in patients; Measurement of primary health care perception in a general population.

Omitting outcomes of importance to patients with chronic kidney disease (CKD) and their caregivers from trials can impede decision-making based on patient-centered outcomes. As part of the global Standardized Outcomes in Nephrology - Chronic Kidney Disease (SONG-CKD) initiative, we aimed to establish a consensus-based set of core outcomes for trials in CKD (prior to the need for kidney replacement therapy). To finalize the proposed set of core outcomes that were identified through focus groups and an international Delphi survey, we convened two international stakeholder workshops in English and Spanish languages that involved 61 patients/caregivers and 75 health professionals from 18 countries. Participants were asked to discuss and endorse the potential core outcomes (mortality, kidney function, life participation, and cardiovascular disease), and to provide suggestions for implementing the core outcomes. The discussions were summarized into four themes: reflecting a comprehensive approach to health, facilitating patient empowerment in their own care, ensuring applicability to broad geographic areas and populations, and feasibility for implementation. Patients, caregivers, and health professionals agreed that mortality, kidney function, life participation and cardiovascular disease should be established as core outcomes for trials in CKD., (Copyright © 2025. Published by Elsevier Inc.)

Background The study aimed to understand the acceptability, satisfaction, uptake, utility and feasibility of a quality improvement (QI) intervention to improve care for coronary heart disease (CHD) patients in Australian primary care practices and identify barriers and enablers, including the impact of COVID-19. Methods Within the QUality improvement for Effectiveness of care for people Living with heart disease (QUEL) study, 26 Australian primary care practices, supported by five Primary Health Networks (PHN) participated in a 1-year QI intervention (November 2019 - November 2020). Data were collected from practices and PHNs staff via surveys and semi-structured interviews. Quantitative and qualitative data were analysed with descriptive statistics and thematic analysis, respectively. Results Feedback was received from 64 participants, including practice team members and PHN staff. Surveys were completed after each of six workshops and at the end of the study. Interviews were conducted with a subgroup of participants (n =9). Participants reported positive satisfaction with individual QI features such as learning workshops and monthly feedback reports. Overall, the intervention was well-received, with most participants expressing interest in participating in similar programs in the future. COVID-19 and lack of time were identified as common barriers, whereas team collaboration and effective leadership enabled practices' participation in the QI program. Additionally, 90% of the practices reported COVID-19 effected their participation due to vaccination rollout, telehealth set-up, and continuous operational review shifting their focus from QI. Conclusion Data-driven QI programs in primary care can boost practice staff confidence and foster increased implementation. Barriers and enablers identified can also support other practices in prioritising effective strategies for future implementation.

Aims: Diagnosis of atrial fibrillation (AF) provides opportunities to reduce stroke risk. This study aimed to compare AF diagnosis rates, participant satisfaction, and feasibility of an electrocardiogram (ECG) self-screening virtual care system with usual care., Methods and Results: This randomized controlled implementation study involving community-dwelling people aged ≥75 years was conducted from May 2021 to June 2023. Participants were given a handheld single-lead ECG device and trained to self-record ECGs once daily on weekdays for 12 months. The control group received usual care with their general practitioners in the first 6 months and participated in the subsequent 6 months. Atrial fibrillation diagnosis and participant satisfaction were assessed at 6 months. Two hundred participants (mean age 79.0 ± 3.4 years; 54.0% female; 72.5% urban) were enrolled. Atrial fibrillation was diagnosed in 10/97 (10.3%) intervention participants and 2/100 (2.0%) in the control group (odds ratio 5.6, 95% confidence interval 1.4-37.3, P = 0.03). In the intervention, 80% of AF cases were diagnosed within 3 months. 91/93 (97.9%) intervention participants and 55/93 (59.1%) control-waitlisted participants (P < 0.001) were satisfied with AF screening. Of the expected 20 days per month, the overall monthly median number of days participants self-recorded ECGs was 20 (interquartile range 17-22). Participants were confident using the device (93%), reported it was easy to use (98%), and found screening efficient (96%)., Conclusion: Patient-led AF self-screening using single-lead ECG devices with a remote central monitoring system was feasible, acceptable, and effective in diagnosing AF among older people. This screening model could be adapted for implementation, interfacing with integrated care models within existing health systems., Registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12621000184875., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To examine the feasibility of implementing remote atrial fibrillation (AF) self-screening among older people supported by a remote central monitoring system., Design: Process evaluation of the Mass AF randomised clinical trial (ACTRN12621000184875) with one-to-one semistructured interviews using interview guides underpinned by the Critical Realism approach and coded using the UK Medical Research Council Guidance of Process Evaluation Framework., Setting and Participants: Community-dwelling people aged ≥75 years from both genders (ratio 1:1) and urban/rural (ratio 2:1) in Australia., Interventions: Participants were provided handheld single-lead electrocardiogram (ECG) devices and trained to self-record ECGs once daily on weekdays for at least 6 months. A remote central team notified participants and general practitioners (GPs) of AF., Primary Feasibility Outcomes: The strengths, weaknesses, opportunities and threats (SWOT) analysis examined enablers (ie, strengths and opportunities) and barriers (ie, weaknesses and threats)., Results: Overall, 200 participants; 98.5% completed the 6-month programme, 96% reported being satisfied with screening and 48 were interviewed: mean age 79 years, 54% male and 71% urban. 11 GPs were interviewed: 55% female and 64% urban. Programme participants trusted the remote monitoring system that supported the screening programme and provided follow-up pathways where required. GPs saw opportunities to introduce this self-screening programme to at-risk patients and improve patients' risk profiles. Programme participants reported that after being trained to use the device, they felt empowered to do self-screening and found it convenient. GPs saw empowerment could enhance the doctor-patient relationship. Participants and GPs valued screening in diagnosing AF that would otherwise be missed in usual care, but the uncertainty of effective screening duration could be a barrier., Conclusions: This screening programme was feasible with the reinforcement of the underpinning enablers. Several implementation strategies were identified using SWOT analysis, including leveraging the opportunity for GPs to introduce this screening programme to at-risk patients., Trial Registration Number: ACTRN12621000184875., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Treatment inertia, non-adherence and non-persistence to medical treatment contribute to poor blood pressure (BP) control worldwide. Fixed dose combination (FDC) antihypertensive medicines simplify prescribing patterns and improve adherence. The aim of this study was to identify factors associated with prescribing FDC antihypertensive medicines and to understand if these factors differ among doctors worldwide., Methods: A cross-sectional survey was conducted online from June 2023 to January 2024 to recruit doctors. We collaborated with an international network of researchers and clinicians identified through institutional connections. A passive snowballing recruitment strategy was employed, where network members forwarded the survey link to their clinical colleagues. The survey instrument, developed through a literature review, interviews with academic and clinical researchers, and pilot testing, assessed participants perspectives on prescribing FDC antihypertensive medicines for hypertension. Participants rated their level of agreement (5-point Likert scale) with statements representing six barriers and four facilitators to FDC use., Findings: Data from 191 surveys were available for analysis. 25% (n = 47) of participants worked in high-income countries, 38% (n = 73) in upper-middle income, 25% (n = 48) in lower-middle income, 6% (n = 10) in low-income countries. Forty percent (n = 70) of participants were between 36-45 years of age; two thirds were male. Cost was reported as a barrier to prescribing FDC antihypertensive medicines [51% (n = 87) agreeing or strongly agreeing], followed by doctors' confidence in BP measured in clinic [40%, (n = 70)], access [37%, (n = 67)], appointment duration [35%, (n = 61)], concerns about side-effects [(21%, n = 37)], and non-adherence [12%, (n = 21)]. Facilitators to FDC antihypertensive polypills prescribing were clinician facing, such as access to educational supports [79%, (n = 143)], more BP measurement data [67%, (n = 120)], a clinical nudge in health records [61%, (n = 109)] and patient-facing including improved patient health literacy [49%, (n = 88)]. The levels of agreement and strong agreement across all barriers and facilitators were similar for participants working in higher or lower income countries. Across all countries, participants rated FDC antihypertensive medications highly valuable for managing patients with non-adherence, (82% reported high or very high value), for patients with high pill burden (80%)., Interpretation: Cost and access were the most common barriers to prescribing FDCs across high- and low-income countries. While greater educational support for clinicians was perceived as the leading potential facilitator of FDC use, this seems unlikely to be effective without addressing access., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in chronic kidney disease (CKD), which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices., Methods: This was an online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals who could read English, Spanish or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a Best-Worst Scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically., Results: In total, 1399 participants from 73 countries completed Round 1 of the Delphi survey, including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization and cardiovascular disease (mean difference >0.3). Consensus was based upon the two groups yielding median scores of ≥7 and mean scores >7, and the proportions of both groups rating the outcome as 'critically important' being >50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences., Conclusion: Across trials in CKD, the outcomes of highest priority to patients, caregivers and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

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.)

Significance: The arterial input function (AIF) plays a crucial role in correcting the time-dependent concentration of the contrast agent within the arterial system, accounting for variations in agent injection parameters (speed, timing, etc.) across patients. Understanding the significance of the AIF can enhance the accuracy of tissue vascular perfusion assessment through indocyanine green-based dynamic contrast-enhanced fluorescence imaging (DCE-FI)., Aim: We evaluate the impact of the AIF on perfusion assessment through DCE-FI., Approach: A total of 144 AIFs were acquired from 110 patients using a pulse dye densitometer. Simulation and patient intraoperative imaging were conducted to validate the significance of AIF for perfusion assessment based on kinetic parameters extracted from fluorescence images before and after AIF correction. The kinetic model accuracy was evaluated by assessing the variability of kinetic parameters using individual AIF versus population-based AIF., Results: Individual AIF can reduce the variability in kinetic parameters, and population-based AIF can potentially replace individual AIF for estimating wash-out rate ( k ep ), maximum intensity ( I max ), ingress slope with lower differences compared with those in estimating blood flow, volume transfer constant ( K trans ), and time to peak., Conclusions: Individual AIF can provide the most accurate perfusion assessment compared with assessment without AIF or based on population-based AIF correction., (© 2024 The Authors.)

Single-pill combination therapy containing four quarter-dose medications for high blood pressure improves BP control compared to monotherapy, however patient-reported acceptance of the quadpill as a treatment strategy remains undescribed. We collected within-trial feedback and interviewed participants from the quadruple ultra-low-dose treatment for hypertension (QUARTET) trial to characterise patient attitudes to this intervention. All trial participants were asked about ease and preference for the quadpill and provided an opportunity to give further comments on the trial at 12 weeks (trial primary endpoint) and 52 weeks extended follow-up. Separately, we used purposive and quota sampling for the semi-structured telephone interviews, with the resultant verbatim transcripts analysed using an inductive thematic analysis approach. Themes were re-evaluated after each successive interview, and at suspected data saturation, an additional interview conducted for confirmation. At 12 weeks follow-up, 502 of 591 (85%) participants responded to acceptability questions, and 359 of 417 (86%) responded at week 52. Most reported the trial capsule easy or very easy to take. From eight sites, 16 participants were interviewed between 5 August 2020 and 19 November 2020. All described a positive experience, preferred once-daily morning dosing and found routine facilitated adherence. Participants valued individual responsibility for adherence, and involvement of the general practitioner in blood-pressure management. Most reported capsule size did not deter adherence but desired a smaller capsule. Participants described a preference for minimising number and dosage of medications, reduced capsule size, and once-daily morning dosing. These findings suggest a preference for single-pill combination therapy for blood pressure lowering., (© 2024. The Author(s).)

Background: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail., Methods: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes., Results: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P  < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P  < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P  < 0.001). The reduction in BP load was also more pronounced with the quadpill., Conclusion: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Mental health is considered an important risk factor affecting the treatment of cardiovascular disease. However, little is known about the use of secondary prevention strategies for CVD in patients with both cancer and CVD. This study aimed to compare the utilisation of primary care chronic disease management plans, mental health care and guideline-indicated cardioprotective medications among CVD patients with and without cancer., Methods: Retrospective cross-sectional study utilising clinical data of patients with CVD from 50 Australian primary care practices. Outcomes included the use of chronic disease management plans, mental health care, guideline-indicated cardioprotective medications and influenza vaccination. Logistic regression, accounting for demographic and clinical covariates and clustering effects by practices, was used to compare the two groups., Results: Of the 15,040 patients with CVD, 1,486 patients (9.9%) concurrently had cancer. Patients with cancer, compared to those without, were older (77.6 vs 71.8 years, p<0.001), more likely to drink alcohol (62.6% vs 55.7%, p<0.001), have lower systolic (130.3±17.8 vs 132.5±21.1 mmHg, p<0.001) and diastolic (72.2±11 vs 75.3±34 mmHg, p<0.001) blood pressure. Although suboptimal for both groups, patients with cancer were significantly more likely to have general practice management plans (GPMPs) (51.4% vs 43.2%, p<0.001), coordination of team care arrangements (TCAs) (46.2% vs 37.0%, p<0.001), have a review of either GPMP or TCA (42.8% vs 34.7%, p<0.001), have a mental health treatment consultation (15.4% vs 10.5%, p=0.004) and be prescribed blood pressure-lowering medications (70.1% vs 66.0%, p=0.002). However, there were no statistical differences in the prescription of lipid-lowering or antiplatelet medications. After adjustments for covariates and multiple testing, patients with cancer did not show a difference in GPMPs, TCAs, and a review of either, but were more likely to receive mental health treatment consultations than those without cancer (odds ratio 1.76; 95% confidence interval 1.42-2.19)., Conclusions: Less than half of patients with CVD had a GPMP, TCA or review of either. Although those patients with cancer were more likely to receive these interventions, still around half the patients did not. Medicare-funded GPMPs, TCAs and a review of either GPMP or TCA were underutilised, and future studies should seek to identify ways of improving access to these services., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Low-dose combinations are a promising intervention for improving blood pressure (BP) control but their effects on therapeutic inertia are uncertain., Methods: Analysis of 591 patients randomized to an ultra-low-dose quadruple pill or initial monotherapy. The episode of therapeutic inertia was defined as a patient visit with a BP of >140/90 mm Hg without intensification of antihypertensive treatment. We compared the frequency of therapeutic inertia episodes between Quadpill and initial monotherapy as a proportion of the total population (intention-to-treat analysis with the denominator being all participants randomized) and as a proportion of people with uncontrolled BP (with the denominator being participants with uncontrolled BP)., Results: Therapeutic inertia occurred in fewer participants randomized to Quadpill compared with monotherapy. For example, among the 390 participants with a 6-month follow-up, therapeutic inertia according to unattended BP was 21/192 (11%) versus 45/192 (23%), P =0.002. There were similar rates of therapeutic inertia among those with uncontrolled unattended BP in each group (all P >0.4). Consistent observations were seen with the use of attended office BP measures. The major determinants of not intensifying treatment during follow-up were BP readings that were close to target and large improvements in BP compared with the previous visit., Conclusions: Among all treated individuals, low-dose Quadpill reduced the number of therapeutic inertia episodes compared with initial monotherapy. After the first follow-up visit, most high BP values did not lead to treatment intensification in both groups. Education is needed about the importance of treatment intensification despite a significant improvement in BP or BP being close to target., Registration: URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12616001144404; Unique identifier: ACTRN12616001144404., Competing Interests: Disclosures The George Institute for Global Health (TGI) has submitted patent applications in respect of low fixed-dose combination products for the treatment of cardiovascular or cardiometabolic disease. A. Rodgers and C. Chow are listed as inventors. A. Rodgers is employed by TGI and seconded part-time to George Medicines Pty Ltd (GM). George Health Enterprises Pty Ltd (GHE) and its subsidiary, GM, have received investment funds to develop fixed-dose combination products, including combinations of blood pressure-lowering drugs. GHE is the social enterprise arm of TGI. A. Rodgers and C. Chow do not have direct financial interests in these patent applications or investments. The other authors report no conflicts.

Objectives: To explore the views of parents and carers regarding the management of acute otitis media in urban Aboriginal and Torres Strait Islander children who are at low risk of complications living in urban communities., Study Design: Qualitative study; semi-structured interviews and short telephone survey., Setting, Participants: Interviews: purposive sample of parents and carers of urban Aboriginal and Torres Strait Islander children (18 months - 16 years old) screened in Aboriginal medical services in Queensland, New South Wales, and Canberra for the WATCH study, a randomised controlled trial that compared immediate antibiotic therapy with watchful waiting for Aboriginal and Torres Strait Islander children with acute otitis media., Survey: parents and carers recruited for the WATCH trial who had completed week two WATCH surveys., Results: We interviewed twenty-two parents and carers, including ten who had declined participation in or whose children were ineligible for the WATCH trial. Some interviewees preferred antibiotics for managing acute otitis media, others preferred watchful waiting, expressing concerns about side effects and reduced efficacy with overuse of antibiotics. Factors that influenced this preference included the severity, duration, and recurrence of infection, and knowledge about management gained during the trial and from personal and often multigenerational experience of ear disease. Participants highlighted the importance of shared decision making by parents and carers and their doctors. Parents and carers of 165 of 262 WATCH participants completed telephone surveys (63%); 81 were undecided about whether antibiotics should always be used for treating acute otitis media. Open-ended responses indicated that antibiotic use should be determined by clinical need, support for general practitioners' decisions, and the view that some general practitioners prescribed antibiotics too often., Conclusions: Parents and carers are key partners in managing acute otitis media in urban Aboriginal and Torres Strait Islander children. Our findings support shared decision making informed by the experience of parents and carers, which could also lead to reduced antibiotic use for managing acute otitis media., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: Profiling patients on a proposed 'immunometabolic depression' (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment., Aims: To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants., Method: Data on 2551 individuals with depression across the iSPOT-D ( n = 967), CO-MED ( n = 665), GENDEP ( n = 773) and EMBARC ( n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses., Results: Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms ( n = 376, β pooled = 0.06, P = 0.049, 95% CI 0.0001-0.12, I 2 = 3.61%); this was also found for an IMD index combining these features ( n = 372, β pooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01-0.22, I 2 = 23.91%), with a higher - but still small - effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (β pooled = 0.16) and the IMD index (β pooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission., Conclusions: Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.

Therapeutic inertia, sometimes referred to as clinical inertia, has been defined as failure to initiate or intensify therapy when therapeutic goals are not reached. Lack of initiation or intensification of treatment according to clinical guidelines has been linked to suboptimal control of a range of chronic conditions. Clinician factors contributing to therapeutic inertia include knowledge gaps; discomfort with uncertainty about the diagnosis, therapeutic target, or evidence; concerns about the safety of treatment intensification; and time constraints. Patient characteristics that may be associated with therapeutic inertia include male sex, older age, lower life expectancy, multiple comorbidities and clinical parameters that are close to target. There may be reasons other than therapeutic inertia that explain apparent undertreatment. Apparent inertia in prescribing may be accompanied by appropriate actions, such as provision of lifestyle advice or interventions to promote adherence to existing medication. Some patients choose not to intensify treatment. Interventions to reduce therapeutic inertia include access to evidence-based treatment guidelines and point-of-care tools, preferably integrated with clinical record systems; clinician education including educational visits; reminders; clinical audits with feedback and reflection on practice; shared decision-making; prompting by patients; and ambulatory or home monitoring (e.g. ambulatory blood pressure monitoring)., Competing Interests: Conflicts of interest: none declared, ((c) Therapeutic Guidelines.)

Background: Little is known about the relationship between patients' cultural and linguistic backgrounds and patient activation, especially in people with diabetes and chronic kidney disease (CKD). We examined the association between culturally and linguistically diverse (CALD) background and patient activation and evaluated the impact of a codesigned integrated kidney and diabetes model of care on patient activation by CALD status in people with diabetes and CKD., Methods: This longitudinal study recruited adults with diabetes and CKD (Stage 3a or worse) who attended a new diabetes and kidney disease service at a tertiary hospital. All completed the patient activation measure at baseline and after 12 months and had demographic and clinical data collected. Patients from CALD backgrounds included individuals who spoke a language other than English at home, while those from non-CALD backgrounds spoke English only as their primary language. Paired t-tests compared baseline and 12-month patient activation scores by CALD status., Results: Patients from CALD backgrounds had lower activation scores (52.1 ± 17.6) compared to those from non-CALD backgrounds (58.5 ± 14.6) at baseline. Within-group comparisons showed that patient activation scores for patients from CALD backgrounds significantly improved by 7 points from baseline to 12 months follow-up (52.1 ± 17.6-59.4 ± 14.7), and no significant change was observed for those from non-CALD backgrounds (58.5 ± 14.6-58.8 ± 13.6)., Conclusions: Among patients with diabetes and CKD, those from CALD backgrounds report worse activation scores. Interventions that support people from CALD backgrounds with comorbid diabetes and CKD, such as the integrated kidney and diabetes model of care, may address racial and ethnic disparities that exist in patient activation and thus improve clinical outcomes., Patient or Public Contribution: Patients, caregivers and national consumer advocacy organisations (Diabetes Australia and Kidney Health Australia) codesigned a new model of care in partnership with healthcare professionals and researchers. The development of the model of care was informed by focus groups of patients and healthcare professionals and semi-structured interviews of caregivers and healthcare professionals. Patients and caregivers also provided a rigorous evaluation of the new model of care, highlighting its strengths and weaknesses., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions., Methods: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement., Conclusions: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care., Trial Registration: ACTRN12622001583730., Competing Interests: Disclosures JES is principal investigator of a National Health and Medical Research Council partnership grant (S0026615) on cardiovascular disease risk assessment; among the partners listed on that grant is a medical technology company that manufactures a central BP monitor. AES received speaker honoraria from device manufacturers, Omron and Aktiia. GSS received consulting and lecture fees from several manufacturers for developing blood pressure measuring technologies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the cost-effectiveness and cost-utility of a quadpill containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg and bisoprolol 2.5 mg in comparison with irbesartan 150 mg for people with hypertension who are either untreated or receiving monotherapy., Methods: We conducted a within-trial and modelled economic evaluation of the Quadruple UltrA-low-dose tReaTment for hypErTension trial. The analysis was preplanned, and medications and health service use captured during the trial. The main outcomes were incremental cost-effectiveness ratios (ICERs) for cost per mm Hg systolic blood pressure (BP) reduction at 3 months, and modelled cost per quality-adjusted life year (QALY) over a lifetime., Results: The within-trial analysis showed no clear difference in cost per mm Hg BP lowering between randomised treatments at 3 months ($A10 (95% uncertainty interval (UI) $A -18 to $A37) per mm Hg per person) for quadpill versus monotherapy. The modelled cost-utility over a lifetime projected a mean incremental cost of $A265 (95% UI $A166 to $A357) and a mean 0.02 QALYs gained (95% UI 0.01 to 0.03) per person with quadpill therapy compared with monotherapy. Quadpill therapy was cost-effective in the base case (ICER of $A14 006 per QALY), and the result was sensitive to the quadpill cost in one-way sensitivity analysis., Conclusions: Quadpill in comparison with monotherapy is comparably cost-effective for short-term BP lowering. In the long-term, quadpill therapy is likely to be cost-effective., Trial Registration Number: ANZCTRN12616001144404., Competing Interests: Competing interests: The George Institute for Global Health (TGI) has submitted patent applications with respect to low fixed-dose combination products for the treatment of cardiovascular or cardiometabolic disease. AR and CKC are listed as inventors. AR is employed by TGI and seconded part-time to George Medicines (GM). George Health Enterprises (GHE) and its subsidiary, GM, have received investment funds to develop fixed-dose combination products, including combinations of blood pressure-lowering drugs. GHE is the social enterprise group of TGI. AR and CKC do not have direct financial interests in these patent applications or investments., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience., Trial Design: The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL)., Conclusion: This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12622000436774. Trial was prospectively registered on March 18, 2022. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383134., Competing Interests: Disclosure G. Bottà is an employee and holds equity in Allelica Srl., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The reasons for the underutilisation of spirometry are unclear. We undertook a systematic review assessing barriers to correct spirometry in Australian general practice., Method: PRISMA guidelines were followed. Six databases (MEDLINE, EMBASE, CINAHL, Scopus, PubMed, Google Scholar) were searched using terms 'primary health care', 'family physicians', 'family practice', 'general practice', 'primary care', 'Australia' and 'spirometry'., Results: The 11 included studies reported multiple barriers to the use of spirometry in Australian general practice. Barriers for clinicians included spirometry having limited clinical utility in general practice (six studies), a reported low confidence with spirometry (six studies) and demonstrated poor spirometry interpretation skills (two studies). Practice-related barriers were time (six studies), cost (four studies), lack of trained staff (four studies), poor availability (four studies) and poor technique/calibration (two studies). Patient reluctance to attend for spirometry (four studies) was also reported as a barrier., Discussion: To reduce barriers to correct spirometry, its perceived low clinical utility and patient reluctance require remediation. Issues of cost, confidence and competence might be addressed by reimbursement settings and ongoing training.

Background: Climate change is impacting the health of individuals worldwide. At the same time, the healthcare sector contributes to carbon emissions. In Australia, healthcare contributes 7% of the country's carbon footprint. Research into the environmental impact and mitigation of carbon emissions in primary care is an emerging area., Objective: To explore staff perspectives on facilitators and barriers to environmental sustainability in 3 Australian general practices seeking to reduce their environmental impact., Methods: We used a qualitative, case-study approach, conducting 23 semistructured interviews with staff across the 3 practices including nurses, administrative staff, and doctors. Observation of systems and staff behaviour relating to environmental sustainability was undertaken at 1 practice. Thematic analysis was conducted to determine themes relating to factors influencing the implementation of environmentally sustainable initiatives within practice settings., Results: Climate mitigation efforts raised by participants were largely focussed on energy and waste reduction, rather than prescribing pharmaceuticals and staff and patient transport. Three main factors influencing change towards sustainable practice were identified: "Leadership," "Staff Engagement and Workplace Culture," and "Concomitant Benefits." A leadership team and workplace culture that valued environmental sustainability were found to be important facilitators, as were concomitant benefits, in particular financial savings. Barriers included what interviewees described as a lack of knowledge about initiatives with the highest impact, lack of understanding described by staff of the evidence behind particular initiatives, waning staff engagement and infection control concerns., Conclusions: Our research highlights several important factors that contribute to the implementation of intended environmentally sustainable initiatives in these 3 practices. Further education, research and high-level policy guidance on the potential environmental impact of prescribing pharmaceuticals, staff and patient transport and unnecessary tests and treatments are recommended to further promote environmental sustainability in primary care., (© The Author(s) 2023. Published by Oxford University Press.)

Vaccines for COVID-19 have allowed countries to combat the spread of the disease. However, new variants have resulted in significant spikes in cases and raised severe health and economic concerns. We present a COVID-19 model to predict coupled effects of vaccine multiple-dose roll-out strategies, vaccine efficacy, waning immunity, population level of caution, sense of safety, under-reporting of cases, and highly prevalent variants such as the Delta (B.1.617.2) and Omicron (B.1.1.529). The modeling framework can incorporate new variants as they emerge to give critical insights into the new cases and guide public policy decision-making concerning vaccine roll-outs and reopening strategies. The model is shown to recreate the history of COVID-19 for five countries (Germany, India, Japan, South Africa, and the United States). Parameters for crucial aspects of the pandemic, such as population behavior, new variants, vaccination, and waning immunity, can be adjusted to predict pandemic scenarios. The model was used to conduct trend analysis to simulate pandemic dynamics taking into account the societal level of caution, societal sense of safety, and the proportions of individuals vaccinated with first, second, and booster doses. We used the results of serological testing studies to estimate the actual number of cases across countries. The model allows quantification of otherwise hard to quantify aspects such as the infectious power of variants and the effectiveness of government mandates and population behavior. Some example cases are presented by investigating the competitive nature of COVID variants and the effect of different vaccine distribution strategies between immunity groups., (© 2022. The Author(s).)