Time to Diagnosis and Treatment for Ovarian Cancer and Associations with Outcomes: A Systematic Review.

Background: Ovarian cancer is commonly diagnosed symptomatically at an advanced stage. Better survival for early disease suggests improving diagnostic pathways may increase survival. This study examines literature assessing diagnostic intervals and their association with clinical and psychological outcomes. Methods: Medline, EMBASE, and EmCare databases were searched for studies including quantitative measures of at least one interval, published between January 1, 2000 and August 9, 2022. Interval measures and associations (interval, outcomes, analytic strategy) were synthesized. Risk of bias of association studies was assessed using the Aarhus Checklist and ROBINS-E tool. Results: In total, 65 papers (20 association studies) were included and 26 unique intervals were identified. Interval estimates varied widely and were impacted by summary statistic used (mean or median) and group focused on. Of Aarhus-defined intervals, patient (symptom to presentation, n = 23; range [median]: 7-168 days) and diagnostic (presentation to diagnosis, n = 22; range [median]: 7-270 days) were most common. Nineteen association studies examined survival or stage outcomes with most, including five low risk-of-bias studies, finding no association. Conclusions: Studies reporting intervals for ovarian cancer diagnosis are limited by inconsistent definitions and reporting. Greater utilization of the Aarhus statement to define intervals and appropriate analytic methods is needed to strengthen findings from future studies.

A scoping review of unexpected weight loss and cancer: risk, guidelines, and recommendations for follow-up in primary care.

BACKGROUND: Cancer diagnoses often begin with consultations with general practitioners (GPs), but the nonspecific nature of symptoms can lead to delayed diagnosis. Unexpected weight loss (UWL) is a common nonspecific symptom linked to undiagnosed cancer, yet guidelines for its diagnostic assessment in general practice lack consistency. AIM: To synthesise evidence on the association between UWL and cancer diagnosis, and to review clinical guidelines and recommendations for assessing patients with UWL. DESIGN AND SETTINGS: Systematic search and analysis of studies conducted in primary care. METHOD: Four databases searched for peer-reviewed literature from 2012 to 2023. Two reviewers conducted all the steps. A narrative review was conducted detailing the evidence for UWL as a risk factor for undiagnosed cancer, existing clinical guidance, and recommended diagnostic approach. RESULTS: We included 25 studies involving 916,092 patients; 92% provided strong evidence of an association between UWL and undiagnosed cancer. The National Institute for Health Care and Excellence Cancer Guideline in the UK was frequently cited. General suggestions encompassed regular weight monitoring, family history, risk factor evaluation, additional signs and symptoms, and a comprehensive physical examination. Commonly recommended pathology tests included C-reactive protein, complete blood count, alkaline phosphatase, and thyroid-stimulating hormone. Immunochemical faecal occult blood test, abdominal ultrasound, and chest X-ray were also prevalent. One large cohort study provided age, sex, and differential diagnosis-specific recommendations. CONCLUSION: This evidence review informs recommendations for investigating patients with UWL and will contribute to a computer decision support tool implementation in primary care, enhancing UWL assessment and potentially facilitating earlier cancer diagnosis.

Trends in primary care blood tests prior to lung and colorectal cancer diagnosis-A retrospective cohort study using linked Australian data.

INTRODUCTION: Abnormal results in common blood tests may occur several months before lung cancer (LC) and colorectal cancer (CRC) diagnosis. Identifying early blood markers of cancer and distinct blood test signatures could support earlier diagnosis in general practice. METHODS: Using linked Australian primary care and hospital cancer registry data, we conducted a cohort study of 855 LC and 399 CRC patients diagnosed between 2001 and 2021. Requests and results from general practice blood tests (six acute phase reactants [APR] and six red blood cell indices [RBCI]) were examined in the 2 years before cancer diagnosis. Poisson regression models were used to estimate monthly incidence rates and examine pre-diagnostic trends in blood test use and abnormal results prior to cancer diagnosis, comparing patterns in LC and CRC patients. RESULTS: General practice blood test requests increase from 7 months before CRC and 6 months before LC diagnosis. Abnormalities in many APR and RBCI tests increase several months before cancer diagnosis, often occur prior to or in the absence of anaemia (in 51% of CRC and 81% of LC patients with abnormalities), and are different in LC and CRC patients. CONCLUSIONS: This study demonstrates an increase in diagnostic activity in Australian general practice several months before LC and CRC diagnosis, indicating potential opportunities for earlier diagnosis. It identifies blood test abnormalities and distinct signatures that are early markers of LC and CRC. If combined with other pre-diagnostic information, these blood tests have potential to support GPs in prioritising patients for cancer investigation of different sites to expedite diagnosis.

Optimising a clinical decision support tool to improve chronic kidney disease management in general practice.

BACKGROUND: Early identification and treatment of chronic disease is associated with better clinical outcomes, lower costs, and reduced hospitalisation. Primary care is ideally placed to identify patients at risk of, or in the early stages of, chronic disease and to implement prevention and early intervention measures. This paper evaluates the implementation of a technological intervention called Future Health Today that integrates with general practice EMRs to (1) identify patients at-risk of, or with undiagnosed or untreated, chronic kidney disease (CKD), and (2) provide guideline concordant recommendations for patient care. The evaluation aimed to identify the barriers and facilitators to successful implementation. METHODS: Future Health Today was implemented in 12 general practices in Victoria, Australia. Fifty-two interviews with 30 practice staff were undertaken between July 2020 and April 2021. Practice characteristics were collected directly from practices via survey. Data were analysed using inductive and deductive qualitative analysis strategies, using Clinical Performance - Feedback Intervention Theory (CP-FIT) for theoretical guidance. RESULTS: Future Health Today was acceptable, user friendly and useful to general practice staff, and supported clinical performance improvement in the identification and management of chronic kidney disease. CP-FIT variables supporting use of FHT included the simplicity of design and delivery of actionable feedback via FHT, good fit within existing workflow, strong engagement with practices and positive attitudes toward FHT. Context variables provided the main barriers to use and were largely situated in the external context of practices (including pressures arising from the COVID-19 pandemic) and technical glitches impacting installation and early use. Participants primarily utilised the point of care prompt rather than the patient management dashboard due to its continued presence, and immediacy and relevance of the recommendations on the prompt, suggesting mechanisms of compatibility, complexity, actionability and credibility influenced use. Most practices continued using FHT after the evaluation phase was complete. CONCLUSIONS: This study demonstrates that FHT is a useful and acceptable software platform that provides direct support to general practice in identifying and managing patients with CKD. Further research is underway to explore the effectiveness of FHT, and to expand the conditions on the platform.

Perceptions of primary care patients on the use of electronic clinical decision support tools to facilitate health care: A systematic review.

OBJECTIVE: Electronic clinical decision support tools (eCDSTs) are interventions designed to facilitate clinical decision-making using targeted medical knowledge and patient information. While eCDSTs have been demonstrated to improve quality of care, there is a paucity of research relating to the acceptability of eCDSTs in primary care from the patients' perspective. This study aims to summarize current evidence relating to primary care patients' perceptions and experiences on the use of eCDSTs by their clinician to provide care. METHODS: Four databases (Medline, Embase, CINAHL and Cochrane Library) were searched for qualitative and quantitative studies with outcomes relating to patients' perceptions of the use of clinician-facing or shared-eCDSTs. Data extraction and critical appraisal using the Johanna Briggs Institute Critical Appraisal checklists were carried out independently by reviewers. Qualitative and quantitative outcomes were synthesized independently. We used Richardson et al. 'Patient Evaluation of Artificial Intelligence (AI) in Healthcare' framework for qualitative analysis. FINDINGS: 20 papers were included for synthesis. eCDSTs were generally well-regarded by patients. The key facilitators for use were promoting informed decision-making, prompting discussions, aiding clinical decision-making, and enabling information sharing. Key barriers for use were lack of holistic care, 'medicalized' language, and confidentiality concerns. CONCLUSION: Our study identified important aspects to consider in the development of future eCDSTs. Patients were generally positive regarding the use of eCDSTs; however, patient's perspectives should be included from the conception of new eCDSTs to ensure recommendations align with the needs of patients and clinicians. PRACTICE IMPLICATIONS: The study results contribute to ensuring the acceptability of eCDSTs for patients and their unique needs. Encouragement is given for future development to adopt and build upon these findings. Additional research focusing on patients' perceptions of using eCDSTs for specific health conditions is deemed necessary.

Cancer in general practice research priorities in Australia.

BACKGROUND AND OBJECTIVES: The Primary Care Collaborative Cancer Clinical Trials Group (PC4) is funded by Cancer Australia to support the development of new cancer in primary care research. We undertook a research prioritisation exercise to identify cancer research priorities in Australian general practice. METHOD: We adapted the nominal group technique, including a literature search and stakeholder survey. An expert group from the Primary Care Collaborative Cancer Clinical Trials Group consolidated and ranked priorities. A second stakeholder survey reviewing the top 50 priorities informed a final prioritisation workshop. RESULTS: Overall, 311 priorities were identified across the cancer continuum. Nearly one-third of priorities were related to cancer survivorship and included strategies to detect recurrence, behavioural interventions and tools to assess physical and psychosocial aspects of survivorship. Prevention/early detection comprised 43.4% of priorities. Palliative care produced the least priorities (9.6%). Cross cutting research priorities (15.1%) included quality and models of care. DISCUSSION: This is the first study to identify cancer research priorities for general practice in Australia. It could be used to inform the development of targeted research and funding to improve the care and outcomes for Australians affected by cancer.

Clinical activity in general practice before sarcoma diagnosis: an Australian cohort study.

BACKGROUND: Increased time to diagnosis in sarcoma is associated with poor prognosis and patient outcomes. Research is needed to identify whether opportunities to expedite the diagnosis of sarcoma in general practice exist. AIM: To examine pre-diagnostic GP clinical activity before sarcoma diagnosis. DESIGN AND SETTING: An Australian retrospective cohort study using hospital registry data (Australian Comprehensive Cancer Outcomes and Research Database [ACCORD]) linked to two primary care datasets (Patron and MedicineInsight). METHOD: The frequency of general practice healthcare utilisation events (general practice attendances, prescriptions, blood test, and imaging requests) were compared in 377 patients with soft tissue sarcoma (STS) and 64 patients with bone sarcoma (BS) in the year pre-diagnosis. Poisson regression models were used to calculate monthly incidence rate ratios (IRR) for the 24 months pre-diagnosis and estimate inflection points for when healthcare use started to increase from baseline. RESULTS: In the 6 months pre-diagnosis, patients with sarcoma had a median of 3-4 general practice attendances, around one-third had a GP imaging request (33% [n = 21] BS and 36% [n = 134] STS), and approximately one in five had multiple imaging requests (19% [n = 12] BS and 21% [n = 80] STS). GP imaging requests progressively increased up to eight-fold from 6 months before sarcoma diagnosis (IRR 8.43, 95% confidence interval [CI] = 3.92 to 18.15, P<0.001) and general practice attendances increased from 3 months pre-diagnosis. CONCLUSION: Patients with sarcoma have increased GP clinical activity from 6 months pre-diagnosis, indicating a diagnostic window where potential opportunities exist for earlier diagnosis. Interventions to help identify patients and promote appropriate use of imaging and direct specialist centre referrals could improve earlier diagnosis and patient outcomes.

Should I Take Aspirin? (SITA): randomised controlled trial of a decision aid for cancer chemoprevention.

BACKGROUND: Australian guidelines recommend that people aged 50-70 years consider taking low-dose aspirin to reduce their risk of colorectal cancer (CRC). AIM: To determine the effect of a consultation with a researcher before an appointment in general practice using a decision aid presenting the benefits and harms of taking low-dose aspirin compared with a general CRC prevention brochure on patients' informed decision making and low-dose aspirin use. DESIGN AND SETTING: Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021. METHOD: Participants were recruited from a consecutive sample of patients aged 50-70 years attending a GP. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk while control consultations discussed reducing CRC risk generally. Self-reported co-primary outcomes were the proportion of individuals making informed choices about taking aspirin at 1 month and on low-dose aspirin uptake at 6 months, respectively. The intervention effect was estimated using a generalised linear model and reported with Bonferroni-adjusted 95% confidence intervals (CIs) and P-values. RESULTS: A total of 261 participants (86% of eligible patients) were randomised into trial arms (n = 129 intervention; n = 132 control). Of these participants, 17.7% (n = 20/113) in the intervention group and 7.6% (n = 9/118) in the control group reported making an informed choice about taking aspirin at 1 month, an estimated 9.1% (95% CI = 0.29 to 18.5) between-arm difference in proportions (odds ratio [OR] 2.47, 97.5% CI = 0.94 to 6.52, P = 0.074). The proportions of individuals who reported taking aspirin at 6 months were 10.2% (n = 12/118) of the intervention group versus 13.8% (n = 16/116) of the control group, an estimated between-arm difference of -4.0% (95% CI = -13.5 to 5.5; OR 0.68 [97.5% CI = 0.27 to 1.70, P = 0.692]). CONCLUSION: The decision aid improved informed decision making but this did not translate into long-term regular use of aspirin to reduce CRC risk. In future research, decision aids should be delivered alongside various implementation strategies.

What are the mechanisms underlying the delivery of survivorship care information in Australia? A realist review.

OBJECTIVE: Quality survivorship information is an essential component of cancer care. However, survivors often report not receiving this information and healthcare professionals report limited practical guidance on how to effectively deliver survivorship information. Therefore, this study used realist review methods to identify mechanisms reported within the published literature for communicating survivorship information and to understand the contextual factors that make these mechanisms effective. METHODS: Full-text papers published in CINAHL, PubMed, Web of Science, Scopus, Cochrane Library, and Academic Search Ultimate were included. Studies included in this review were conducted in Australia between January 2006 and December 2023, and reported on how information regarding survivorship care was communicated to adult cancer survivors living in the community. This review utilized realist methodologies: text extracts were converted to if-then statements used to generate context-mechanism-outcome theories. RESULTS: Fifty-one studies were included and six theories for mechanisms that underpin the effective delivery of survivorship information were formed. These include: (1) tailoring information based on the survivors' background, (2) enhancing communication among providers, (3) employing dedicated survivorship staff, (4) providing survivorship training, (5) reducing the burden on survivors to navigate their care, and (6) using multiple modalities to provide information. CONCLUSIONS: Findings can inform practical guidance for how survivorship care information is best delivered in practice. Clinicians can apply this guidance to improve their individual interactions with cancer survivors, as can policymakers to develop healthcare systems and procedures that support effective communication of cancer survivorship information.

Discussions with patients about referral pathways and costs in the diagnosis and treatment of colorectal cancer in Victoria, Australia.

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) survival in Australia differs by health insurance status, but why this occurs is uncertain. There are growing concerns about out-of-pocket healthcare costs. We examined patient experiences of referral pathways to diagnosis and treatment of CRC in Victoria, Australia, and discussions about costs, comparing public, private and mixed healthcare system users. METHOD: Semistructured telephone interviews were conducted with 16 purposively sampled, English-speaking patients aged ≥40 years with CRC. Interviews were recorded, transcribed and analysed thematically. RESULTS: Private patients described greater out-of-pocket expenses balanced by greater choice of provider and access. Public patients perceived limited choice in their diagnostic or treatment provider, although some considered switching systems. Patients trusted their general practitioner or specialist for referrals. Discussions about costs did not meet guideline recommendations. DISCUSSION: There are limited opportunities for informed decision making about public versus private care for cancer diagnosis and treatment, which could contribute to inequalities in outcomes.

Patient preferences for investigating cancer-related symptoms in Australian general practice: a discrete-choice experiment.

BACKGROUND: Striking the right balance between early cancer diagnosis and the risk of excessive testing for low-risk symptoms is of paramount importance. Patient-centred care must also consider patient preferences for testing. AIM: To investigate the diagnostic testing preferences of the Australian public for symptoms associated with oesophagogastric (OG), bowel, or lung cancer. DESIGN AND SETTING: One of three discrete-choice experiments (DCEs) related to either OG, bowel, or lung cancer were administered to a nationally representative sample of Australians aged ≥40 years. METHOD: Each DCE comprised three scenarios with symptom positive predictive values (PPVs) for undiagnosed cancer ranging from 1% to 3%. The numerical risk was concealed from participants. DCE attributes encompassed the testing strategy, GP familiarity, test and result waiting times, travel duration, and test cost. Preferences were estimated using conditional and mixed logit models. RESULTS: A total of 3013 individuals participated in one of three DCEs: OG (n = 1004), bowel (n = 1006), and lung (n = 1003). Preferences were chiefly driven by waiting time and test cost, followed by the test type. There was a preference for more invasive tests. When confronted with symptoms carrying an extremely low risk (symptom PPV of ≤1%), participants were more inclined to abstain from testing. CONCLUSION: Access-related factors, particularly waiting times and testing costs, emerged as the most pivotal elements influencing preferences, underscoring the substantial impact of these systemic factors on patient choices regarding investigations.

Primary care practice-based interventions and their effect on participation in population-based cancer screening programs: a systematic narrative review.

AIM: To provide a systematic synthesis of primary care practice-based interventions and their effect on participation in population-based cancer screening programs. BACKGROUND: Globally, population-based cancer screening programs (bowel, breast, and cervical) have sub-optimal participation rates. Primary healthcare workers (PHCWs) have an important role in facilitating a patient's decision to screen; however, barriers exist to their engagement. It remains unclear how to best optimize the role of PHCWs to increase screening participation. METHODS: A comprehensive search was conducted from January 2010 until November 2023 in the following databases: Medline (OVID), EMBASE, and CINAHL. Data extraction, quality assessment, and synthesis were conducted. Studies were separated by whether they assessed the effect of a single-component or multi-component intervention and study type. FINDINGS: Forty-nine studies were identified, of which 36 originated from the USA. Fifteen studies were investigations of single-component interventions, and 34 studies were of multi-component interventions. Interventions with a positive effect on screening participation were predominantly multi-component, and most included combinations of audit and feedback, provider reminders, practice-facilitated assessment and improvement, and patient education across all screening programs. Regarding bowel screening, provision of screening kits at point-of-care was an effective strategy to increase participation. Taking a 'whole-of-practice approach' and identifying a 'practice champion' were found to be contextual factors of effective interventions.The findings suggest that complex interventions comprised of practitioner-focused and patient-focused components are required to increase cancer screening participation in primary care settings. This study provides novel understanding as to what components and contextual factors should be included in primary care practice-based interventions.

Increasing bowel cancer screening using SMS in general practice: the SMARTscreen cluster randomised trial.

BACKGROUND: Australia has one of the highest incidences of colorectal cancer (CRC) worldwide. The Australian National Bowel Cancer Screening Program (NBCSP) is a best-practice, organised screening programme, but uptake is low (40.9%) and increasing participation could reduce morbidity and mortality associated with CRC. Endorsement by GPs is strongly associated with increasing screening uptake. AIM: This study (SMARTscreen) aimed to test whether a multi-intervention short message service (SMS) sent by general practices to 50-60-year-old patients who were due to receive the NBCSP kit would increase NBCSP uptake, by comparing it with usual care. DESIGN AND SETTING: A stratified cluster randomised controlled trial was undertaken, involving 21 Australian general practices in Western Victoria, Australia. METHOD: For intervention practices, people due to receive the NBCSP kit within a 6-month study period were sent an SMS just before receiving the kit. The SMS included a personalised message from the person's general practice endorsing the kit, a motivational narrative video, an instructional video, and a link to more information. Control practices continued with usual care, comprising at-home testing with a faecal immunochemical test (FIT) through the NBCSP. The primary outcome was the between-arm percentage difference in uptake of FIT screening within 12 months from randomisation, which was estimated using generalised linear model regression. RESULTS: In total, 39.2% (1143/2914) of people in 11 intervention practices and 23.0% (583/2537) of people in 10 control practices had a FIT result in their electronic health records - a difference of 16.5% (95% confidence interval = 2.02 to 30.9). CONCLUSION: The SMS intervention increased NBCSP kit return in 50-60-year-old patients in general practice. This finding informed a larger trial - SMARTERscreen - to test this intervention in a broader Australian population.

Colorectal cancer survivors' experiences and views of shared and telehealth models of survivorship care: A qualitative study.

OBJECTIVES: The number of colorectal cancer (CRC) survivors is increasing and current models of survivorship care are unsustainable. There is a drive to implement alternative models of care including shared care between general practitioners (GPs) and hospital-based providers. The primary objective of this study was to explore perspectives on facilitators and barriers to shared care. The secondary objective was to explore experiences of telehealth-delivered care. METHOD: Qualitative data were collected via semi-structured interviews with participants in the Shared Care for Colorectal Cancer Survivors (SCORE) randomised controlled trial. Interviews explored patient experiences of usual and shared survivorship care during the SCORE trial. In response to the COVID pandemic, participant experiences of telehealth appointments were also explored. Interviews were recorded and transcribed for thematic analysis. RESULTS: Twenty survivors of CRC were interviewed with an even number in the shared and usual care arms; 14 (70%) were male. Facilitators to shared care included: good relationships with GPs; convenience of GPs; good communication between providers; desire to reduce public health system pressures. Barriers included: poor communication between clinicians; inaccessibility of GPs; beliefs about GP capacity; and a preference for follow-up care with the hospital after positive treatment experiences. Participants also commonly expressed a preference for telehealth-based follow-up when there was no need for a clinical examination. CONCLUSIONS: This is one of few studies that have explored patient experiences with shared and telehealth-based survivorship care. Findings can guide the implementation of these models, particularly around care coordination, communication, preparation, and personalised pathways of care.

SCORE: a randomised controlled trial evaluating shared care (general practitioner and oncologist) follow-up compared to usual oncologist follow-up for survivors of colorectal cancer.

Background: SCORE is the first randomised controlled trial (RCT) to examine shared oncologist and general practitioner (GP) follow-up for survivors of colorectal cancer (CRC). SCORE aimed to show that shared care (SC) was non-inferior to usual care (UC) on the EORTC QLQ-C30 Global Health Status/Quality of Life (GHQ-QoL) scale to 12 months. Methods: The study recruited patients from five public hospitals in Melbourne, Australia between February 2017 and May 2021. Patients post curative intent treatment for stage I-III CRC underwent 1:1 randomisation to SC and UC. SC replaced two oncologist visits with GP visits and included a survivorship care plan and primary care management guidelines. Assessments were at baseline, 6 and 12 months. Difference between groups on GHQ-QoL to 12 months was estimated from a mixed model for repeated measures (MMRM), with a non-inferiority margin (NIM) of -10 points. Secondary endpoints included quality of life (QoL); patient perceptions of care; costs and clinical care processes (CEA tests, recurrences). Registration ACTRN12617000004369p. Findings: 150 consenting patients were randomised to SC (N = 74) or UC (N = 76); 11 GPs declined. The mean (SD) GHQ-QoL scores at 12 months were 72 (20.2) for SC versus 73 (17.2) for UC. The MMRM mean estimate of GHQ-QoL across the 6 month and 12 month follow-up was 69 for SC and 73 for UC, mean difference -4.0 (95% CI: -9.0 to 0.9). The lower limit of the 95% CI did not cross the NIM. There was no clear evidence of differences on other QoL, unmet needs or satisfaction scales. At 12 months, the majority preferred SC (40/63; 63%) in the SC group, with equal preference for SC (22/62; 35%) and specialist care (22/62; 35%) in UC group. CEA completion was higher in SC. Recurrences similar between arms. Patients in SC on average incurred USD314 less in health costs versus UC patients. Interpretation: SC seems to be an appropriate and cost-effective model of follow-up for CRC survivors. Funding: Victorian Cancer Agency and Cancer Australia.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

SMARTERscreen protocol: a three-arm cluster randomised controlled trial of patient SMS messaging in general practice to increase participation in the Australian National Bowel Cancer Screening Program.

BACKGROUND: Australia persistently has one of the highest rates of colorectal cancer (CRC) in the world. Australia's National Bowel Cancer Screening Program (NBCSP) sends a biennial Faecal Immunochemical Test (FIT)-the 'NBCSP kit'-to everyone eligible for the programme between 50 and 74 years old; however, participation in the programme is low, especially in the 50- to 60-year-old age group. Our previous efficacy trial ('SMARTscreen') demonstrated an absolute increase in uptake of 16.5% (95% confidence interval = 2.02-30.9%) for people sent an SMS with motivational and instructional videos, from their general practice prior to receiving their NBCSP kit, compared to those receiving usual care. Building on the strengths of the SMARTscreen trial and addressing limitations, the 'SMARTERscreen' trial will test the effect on participation in the NBCSP of sending either an SMS only or an SMS with online video material to general practice patients due to receive their NBCSP compared to 'usual care'. METHODS: SMARTERscreen is a three-arm stratified cluster randomised controlled trial involving 63 general practices in two states in Australia. Eligible patients are patients who are aged 49-60 years and due to receive their NBCSP kit within the next 2 weeks during the intervention period. General practices will be equally randomised to three trial arms (21:21:21, estimated average 260 patients/practice). The two interventions include (i) an SMS with an encouraging message from their general practice or (ii) the same SMS with weblinks to additional motivational and instructional videos. The control arm will receive 'usual care'. Using the intention-to-treat approach, primary analysis will estimate the three pair-wise between-arm differences in the proportion of eligible patients who participate in the NBCSP within 6 months of when their kit is sent, utilising screening data from the Australian National Cancer Screening Register (NCSR). Patient intervention adherence to the interventions will also be evaluated. Findings will be incorporated into the Policy1-Bowel microsimulation model to estimate the long-term health benefits and cost-effectiveness of the interventions. DISCUSSION: SMARTERscreen will provide high-level evidence determining whether an SMS or an SMS with web-based material sent to general practice patients prior to receiving their NBCSP kit increases participation in bowel cancer screening. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000036617. Registered on 13 January 2023. Trial URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385119&isClinicalTrial=False.