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Background Hepatocellular carcinoma (HCC) incidence and mortality rates are increasing at a greater pace than any other cancer in Australia. Cirrhosis is the major risk factor for HCC, and early detection of HCC through surveillance of people with cirrhosis can improve outcomes. However, cirrhosis is under-detected in primary care settings, with 60% of patients diagnosed with HCC having unrecognised cirrhosis and not found to be in a surveillance programme. Targeted screening of at-risk populations in primary care using noninvasive tests for liver fibrosis could lead to improved diagnosis of cirrhosis and increased participation in HCC surveillance programmes. Methods This is a prospective multicentre parallel randomised controlled trial of 2470 participants, to evaluate the impact of a cirrhosis detection and hepatocellular carcinoma surveillance pathway compared to usual care in 45–75 year olds, with risk factors for chronic liver disease, from regional and urban general practice clinics, across four Australian states. Participants will be randomised 1:1, to usual general practitioner care (control) or a cirrhosis detection pathway (intervention), stratified by clinic and potential hazardous drinking. The cirrhosis detection intervention consists of liver fibrosis blood tests (comprising the Fibrosis-4 Index and Hepascore) and a liver stiffness measurement conducted by FibroScan in those with elevated liver fibrosis blood markers. Participants with elevated FibroScan® values will be recommended for referral for hepatology assessment to determine the need for HCC surveillance. The primary outcome is the between-arm difference in proportion of participants with newly diagnosed cirrhosis in HCC surveillance at 12 months. Secondary outcomes at 12 months will include the between-arm difference in proportion of participants with a diagnosis of any stage HCC, diagnoses of advanced fibrosis and liver decompensation and mean anxiety state and mean quality of life. The cost-effectiveness of the cirrhosis detection pathway will be determined using data linkage to state and national health datasets. Process evaluation will involve assessment of the optimal cirrhosis detection pathway, along with the barriers and enablers of implementation of this pathway, assessed by participant interviews. Discussion This trial will provide evidence of the efficacy and cost-effectiveness of a cirrhosis detection pathway in Australian general practice settings. This will provide evidence to guide the early identification and appropriate placement of patients in HCC surveillance programmes, resulting in earlier HCC diagnosis and improved outcomes. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12622000185763p. Registered on 3rd February 2022.

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

The majority of patients with respiratory illness are seen in primary care settings. Given COVID-19 is predominantly a respiratory illness, the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), assessed the pandemic impact on primary care visits for respiratory illnesses. Definitions for respiratory illness types were agreed on collectively. Monthly visit counts with diagnosis were shared centrally for analysis. Primary care settings in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden and the United States. Over 38 million patients seen in primary care settings in INTRePID countries before and during the pandemic, from January 1st, 2018, to December 31st, 2021. Relative change in the monthly mean number of visits before and after the onset of the pandemic for acute infectious respiratory disease visits including influenza, upper and lower respiratory tract infections and chronic respiratory disease visits including asthma, chronic obstructive pulmonary disease, respiratory allergies, and other respiratory diseases. INTRePID countries reported a marked decrease in the average monthly visits for respiratory illness. Changes in visits varied from -10.9% [95% confidence interval (CI): -33.1 to +11.3%] in Norway to -79.9% (95% CI: -86.4% to -73.4%) in China for acute infectious respiratory disease visits and - 2.1% (95% CI: -12.1 to +7.8%) in Peru to -59.9% (95% CI: -68.6% to -51.3%) in China for chronic respiratory illness visits. While seasonal variation in allergic respiratory illness continued during the pandemic, there was essentially no spike in influenza illness during the first 2 years of the pandemic. The COVID-19 pandemic had a major impact on primary care visits for respiratory presentations. Primary care continued to provide services for respiratory illness, although there was a decrease in infectious illness during the COVID pandemic. Understanding the role of primary care may provide valuable information for COVID-19 recovery efforts and planning for future global emergencies.

BackgroundAlthough most young Australians visit their general practitioner at least once a year, discrepancies remain between healthcare need and healthcare support in this group. A detailed contemporary understanding of youth presentations to general practice is needed, given that the last comprehensive investigation into Australian adolescent encounters with primary care is now over two decades old. The aim of this study is to describe rates of presentation and reasons for visit among young people in Victorian primary care using data extracted from electronic medical records.MethodsA retrospective descriptive study of de-identified electronic medical records data from >22,000 adolescents aged 10–24 years who presented to Victorian general practice in 2019 was undertaken.ResultsThe overall mean attendance rate of young people was 2.89 visits/patient per year, with rates highest amongst older patients, females and those in regional localities. Young people presented most frequently for physical (biomedical) concerns (such as respiratory, skin and general physical complaints), and psychological (mental health) reasons for visit.ConclusionsThe study addresses a significant gap in our understanding of the role of general practice for young Australians. Although physical problems continue to predominate among Australian adolescents’ reasons for visit to general practice, psychological presentations occur much more frequently than estimated in past studies. This study also demonstrates that general practice electronic medical records data can be harnessed to provide a meaningful description of primary care activity.

Umbilical-cord blood (UCB) is increasingly considered as an alternative to peripheral blood progenitor cells (PBPCs) or bone marrow, especially when an HLA-matched adult unrelated donor is not available. We aimed to determine the optimal role of UCB grafts in transplantation for adults with acute leukaemia, and to establish whether current graft-selection practices are appropriate. We used Cox regression to retrospectively compare leukaemia-free survival and other outcomes for UCB, PBPC, and bone marrow transplantation in patients aged 16 years or over who underwent a transplant for acute leukaemia. Data were available on 1525 patients transplanted between 2002 and 2006. 165 received UCB, 888 received PBPCs, and 472 received bone marrow. UCB units were matched at HLA-A and HLA-B at antigen level, and HLA-DRB1 at allele level (n=10), or mismatched at one (n=40) or two (n=115) antigens. PBPCs and bone-marrow grafts from unrelated adult donors were matched for allele-level HLA-A, HLA-B, HLA-C, and HLA-DRB1 (n=632 and n=332, respectively), or mismatched at one locus (n=256 and n=140, respectively). Leukaemia-free survival in patients after UCB transplantation was comparable with that after 8/8 and 7/8 allele-matched PBPC or bone-marrow transplantation. However, transplant-related mortality was higher after UCB transplantation than after 8/8 allele-matched PBPC recipients (HR 1·62, 95% CI 1·18–2·23; p=0·003) or bone-marrow transplantation (HR 1·69, 95% CI 1·19–2·39; p=0·003). Grades 2–4 acute and chronic graft-versus-host disease (GvHD) were lower in UCB recipients compared with allele-matched PBPC (HR 0·57, 95% 0·42–0·77; p=0·002 and HR 0·38, 0·27–0·53; p=0·003, respectively), while the incidence of chronic, but not acute GvHD, was lower after UCB than after 8/8 allele-matched bone-marrow transplantation (HR 0·63, 0·44–0·90; p=0·01). These data support the use of UCB for adults with acute leukaemia when there is no HLA-matched unrelated adult donor available, and when a transplant is needed urgently. National Cancer Institute, National Heart Lung and Blood Institute, National Institute of Allergy and Infectious Disease ( U24-CA76518); Health Resources and Services Administration ( HHSH234200637015C); Office of Naval Research, Department of Navy ( N00014-08-1-1207); Children's Leukemia Research Association; and a Scholar in Clinical Research Award from the Leukemia and Lymphoma Society.

The quantum theory of linearized perturbations of the gravitational field of a Schwarzschild black hole is presented. The fundamental operators are seen to be the perturbed Weyl scalars \\(\\dot\\Psi_0\\) and \\(\\dot\\Psi_4\\) associated with the Newman-Penrose description of the classical theory. Formulae are obtained for the expectation values of the modulus squared of these operators in the Boulware, Unruh and Hartle-Hawking quantum states. Differences between the renormalized expectation values of both \\(\\bigl| \\dot\\Psi_0 \\bigr|^2\\) and \\(\\bigl| \\dot\\Psi_4 \\bigr|^2\\) in the three quantum states are evaluated numerically.