Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes.

This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures.

Ethics approval was received from the Royal Children’s Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences.

ACTRN12621000920897; Pre-results.

Among people experiencing severe and multiple disadvantage (SMD), poor oral health is common and linked to smoking, substance use and high sugar intake. Studies have explored interventions addressing oral health and related behaviours; however, factors related to the implementation of these interventions remain unclear. This mixed-methods systematic review aimed to synthesise evidence on the implementation and sustainability of interventions to improve oral health and related health behaviours among adults experiencing SMD.

Bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature were searched from inception to February 2023. Studies meeting the inclusion criteria were screened and extracted independently by two researchers. Quality appraisal was undertaken, and results were synthesised using narrative and thematic analyses.

Seventeen papers were included (published between 1995 and 2022). Studies were mostly of moderate quality and included views from SMD groups and service providers. From the qualitative synthesis, most findings were related to aspects such as trust, resources and motivation levels of SMD groups and service providers. None of the studies reported on diet and none included repeated offending (one of the aspects of SMD). From the quantitative synthesis, no difference was observed in programme attendance between the interventions and usual care, although there was some indication of sustained improvements in participation in the intervention group.

This review provides some evidence that trust, adequate resources and motivation levels are potentially important in implementing interventions to improve oral health and substance use among SMD groups. Further research is needed from high quality studies and focusing on diet in this population.

CRD42020202416.

To create case definitions for confirmed COVID-19 diagnoses, COVID-19 vaccination status and three separate definitions of high risk of severe COVID-19, as well as to assess whether the implementation of these definitions in a cohort reflected the sociodemographic and clinical characteristics of COVID-19 epidemiology in England.

Retrospective cohort study.

Electronic healthcare records from primary care (Clinical Practice Research Datalink, CPRD) linked to secondary care data (Hospital Episode Statistics) data covering 24% of the population in England.

2 271 072 persons aged 1 year and older diagnosed with COVID-19 in CPRD Aurum between 1 August 2020 and 31 January 2022.

Age, sex and regional distribution of COVID-19 cases and COVID-19 vaccine doses received prior to diagnosis were assessed separately for the cohorts of cases identified in primary care and those hospitalised for COVID-19 (primary diagnosis code of ICD-10 U07.1 ‘COVID-19’). Smoking status, body mass index and Charlson Comorbidity Index were compared for the two cohorts, as well as for three separate definitions of high risk of severe disease used in the UK (National Health Service Highest Risk, PANORAMIC trial eligibility, UK Health Security Agency Clinical Risk prioritisation for vaccination).

Compared with national estimates, CPRD case estimates under-represented older adults in both the primary care (age 65–84: 6% in CPRD vs 9% nationally) and hospitalised (31% vs 40%) cohorts, and over-represented people living in regions with the highest median wealth areas of England (20% primary care and 20% hospital admitted cases in South East vs 15% nationally). The majority of non-hospitalised cases and all hospitalised cases had not completed primary series vaccination. In primary care, persons meeting high-risk definitions were older, more often smokers, overweight or obese, and had higher Charlson Comorbidity Index score.

CPRD primary care data are a robust real-world data source and can be used for some COVID-19 research questions, however, limitations of the data availability should be carefully considered. Included in this publication are supplemental files for a total of over 28 000 codes to define each of three definitions of high risk of severe disease.

Evidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies and overtreatment. However, diagnostic accuracy studies have shown that detection of clinically insignificant prostate cancer can be reduced by MRI combined with targeted biopsies.

The aim of the paper is to describe the analysis of the ProScreen randomised trial to assess the performance of the novel screening algorithm in terms of the primary outcome, prostate cancer mortality and secondary outcomes as intermediate indicators of screening benefits and harms of screening.

The trial aims to recruit at least 111 000 men to achieve sufficient statistical power for the primary outcome. Men will be allocated in a 1:3 ratio to the screening and control arms. Interim analysis is planned at 10 years of follow-up, and the final analysis at 15 years. Difference between the trial arms in prostate cancer mortality will be assessed by Gray’s test using intention-to-screen analysis of randomised men. Secondary outcomes will be the incidence of prostate cancer by disease aggressiveness, progression to advanced prostate cancer, death due to any cause and cost-effectiveness of screening.

The trial protocol was reviewed by the ethical committee of the Helsinki University Hospital (2910/2017). Results will be disseminated through publications in international peer-reviewed journals and at scientific meetings.

NCT03423303

This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH).

Retrospective observational study.

Pulmonary hypertension referral centre in the UK.

Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis.

Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed.

Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6–18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients.

Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

To assess the impact of the COVID-19 pandemic on prescription drug use and costs.

Interrupted time series analysis of comprehensive administrative health data linkages in British Columbia, Canada, from 1 January 2018 to 28 March 2021.

Retrospective population-based analysis of all prescription drugs dispensed in community pharmacies and outpatient hospital pharmacies and irrespective of the drug insurance payer.

Between 4.30 and 4.37 million individuals (52% women) actively registered with the publicly funded medical services plan.

COVID-19 pandemic and associated mitigation measures.

Weekly dispensing rates and costs, both overall and stratified by therapeutic groups and pharmacological subgroups, before and after the declaration of the public health emergency related to the COVID-19 pandemic. Relative changes in post-COVID-19 outcomes were expressed as ratios of observed to expected rates.

After the onset of the pandemic and subsequent COVID-19 mitigation measures, overall medication dispensing rates dropped by 2.4% (p

The COVID-19 pandemic impact on prescription drug dispensing was heterogeneous across medication subgroups. As data become available, dispensing trends in nervous system agents, antibiotics and antivirals warrant further monitoring and investigation.

To quantify direct costs and healthcare resource utilisation (HCRU) associated with acute COVID-19 in adults in England.

Population-based retrospective cohort study using Clinical Practice Research Datalink Aurum primary care electronic medical records linked to Hospital Episode Statistics secondary care administrative data.

Patients registered to primary care practices in England.

1 706 368 adults with a positive SARS-CoV-2 PCR or antigen test from August 2020 to January 2022 were included; 13 105 within the hospitalised cohort indexed between August 2020 and March 2021, and 1 693 263 within the primary care cohort indexed between August 2020 and January 2022. Patients with a COVID-19-related hospitalisation within 84 days of a positive test were included in the hospitalised cohort.

Primary and secondary care HCRU and associated costs ≤4 weeks following positive COVID-19 test, stratified by age group, risk of severe COVID-19 and immunocompromised status.

Among the hospitalised cohort, average length of stay, including critical care stays, was longer in older adults. Median healthcare cost per hospitalisation was higher in those aged 75–84 (£8942) and ≥85 years (£8835) than in those aged

COVID-19-related hospitalisations in older adults, particularly critical care stays, were the primary drivers of high COVID-19 resource use in England. These findings may inform health policy decisions and resource allocation in the prevention and management of COVID-19.

Chronic kidney disease (CKD) is increasingly recognised as a growing global public health problem. Early detection and management can significantly reduce the loss of kidney function. The proposed trial aims to evaluate the impact of a community pharmacy-led intervention combining CKD screening and medication review on CKD detection and quality use of medicines (QUM) for patients with CKD. We hypothesise that the proposed intervention will enhance detection of newly diagnosed CKD cases and reduce potentially inappropriate medications use by people at risk of or living with CKD.

This study is a multicentre, pragmatic, two-level cluster randomised controlled trial which will be conducted across different regions in Australia. Clusters of community pharmacies from geographical groups of co-located postcodes will be randomised. The project will be conducted in 122 community pharmacies distributed across metropolitan and rural areas. The trial consists of two arms: (1) Control Group: a risk assessment using the QKidney CKD risk assessment tool, and (2) Intervention Group: a risk assessment using the QKidney CKD plus Point-of-Care Testing for kidney function markers (serum creatinine and estimated glomerular filtration rate), followed by a QUM service. The primary outcomes of the study are the proportion of patients newly diagnosed with CKD at the end of the study period (12 months); and rates of changes in the number of medications considered problematic in kidney disease (number of medications prescribed at inappropriate doses based on kidney function and/or number of nephrotoxic medications) over the same period. Secondary outcomes include proportion of people on potentially inappropriate medications, types of recommendations provided by the pharmacist (and acceptance rate by general practitioners), proportion of people who were screened, referred, and took up the referral to visit their general practitioners, and economic and other patient-centred outcomes.

The trial protocol has been approved by the Human Research Ethics Committee at the University of Sydney (2022/044) and the findings of the study will be presented at scientific conferences and published in peer-reviewed journal(s).

Australian New Zealand Clinical Trials Registry (ACTRN12622000329763).

Chronic malnutrition is a serious problem in southern Angola with a prevalence of 49.9% and 37.2% in the provinces of Huila and Cunene, respectively. The MuCCUA (Mother and Child Chronic Undernutrition in Angola) trial is a community-based randomised controlled trial (c-RCT) which aims to evaluate the effectiveness of a nutrition supplementation plus standard of care intervention and a cash transfer plus standard of care intervention in preventing stunting, and to compare them with a standard of care alone intervention in southern Angola. This protocol describes the planned economic evaluation associated with the c-RCT.

We will conduct a cost-efficiency and cost-effectiveness analysis nested within the MuCCUA trial with a societal perspective, measuring programme, provider, participant and household costs. We will collect programme costs prospectively using a combined calculation method including quantitative and qualitative data. Financial costs will be estimated by applying activity-based costing methods to accounting records using time allocation sheets. We will estimate costs not included in accounting records by the ingredients approach, and indirect costs incurred by beneficiaries through interviews, household surveys and focus group discussions. Cost-efficiency will be estimated as cost per output achieved by combining activity-specific cost data with routine data on programme outputs. Cost-effectiveness will be assessed as cost per stunting case prevented. We will calculate incremental cost-effectiveness ratios comparing the additional cost per improved outcome of the different intervention arms and the standard of care. We will perform sensitivity analyses to assess robustness of results.

This economic evaluation will provide useful information to the Angolan Government and other policymakers on the most cost-effective intervention to prevent stunting in this and other comparable contexts. The protocol was approved by the República de Angola Ministério da Saúde Comité de Ética (27C.E/MINSA.INIS/2022). The findings of this study will be disseminated within academia and the wider policy sphere.

ClinicalTrials.gov Registry (NCT05571280).

Preoperative anxiety is a frequent problem that can lead to complications both during anaesthesia and in the postoperative period, especially in oncology. Studies have shown that it can be managed using non-pharmacological approaches, but few works have evaluated psychoeducational programmes. The aim of the COHErence Cardiaque (COHEC) II Study is to evaluate the combination of medical hypnosis (MH) and cardiac coherence (CC) training to manage preoperative anxiety in patients with cancer.

COHEC II is an ongoing multicentre randomised clinical trial carried out in three French comprehensive cancer centres. In total, 296 patients who will undergo surgery for cancer will be recruited during 18 months and will be randomised in the control arm or the intervention arm. Patients in the intervention arm will follow a daily programme that combines MH and CC, starting 7 days before surgery. The control arm will receive the standard treatment to manage preoperative anxiety. The primary endpoint is the anxiety level on surgery day, measured using a Visual Analogue Scale. Secondary endpoints are patient adherence to the programme, satisfaction and postsurgery recovery quality.

The study protocol was approved by the French Ethics Committee (Comité de Protection des Personnes EST-II) on 24 November 2021 and will be carried out following the good practice guidelines and the Declaration of Helsinki. Results will be published in peer-reviewed journals and presented at conferences.

NCT05197972.

Despite young carers (YCs) providing regular and significant care that exceeds what would normally be associated with an adult caregiver, we need to learn more about their experience interacting with the healthcare system. The primary study aims were to (1) describe YC experiences in interacting with the healthcare system and (2) identify types of support YC recognise as potentially helpful to their caring role.

A mixed-methods qualitative study was conducted between March 2022 and August 2022, comprising two phases of (1) semi-structured interviews and focus groups with YCs living in the community to confirm and expand earlier research findings, and (2) a co-design workshop informed by a generative research approach. We used findings from the interviews and focus groups to inform the brainstorming process for identifying potential solutions.

Eight YCs completed either a focus group or an interview, and four continued the study and participated in the co-design activity with 12 participants. Phase 1 resulted in three overarching themes: (1) navigating the YC role within the healthcare system; (2) being kept out of the loop; and (3) normalising the transition into caregiving. Phase 2 identified two categories: (1) YC-focused supports and (2) raising awareness and building capacity in the healthcare system.

Study findings revealed the critical role that YCs play when supporting their families during pivotal interactions in the healthcare system. Like their older caregiver counterparts, YCs struggle to navigate, coordinate and advocate for their family members while juggling their needs as they transition from adolescence to adulthood. This study provides important preliminary insights into YCs encountering professionals, which can be used to design and implement national support structures.