Risultati per: Cardio-oncology: rivista open access

Introduction
New-onset supraventricular arrhythmia (NOSVA) is the most common arrhythmia in patients with septic shock and is associated with haemodynamic alterations and increased mortality rates. With no data available from randomised trials, clinical practice for patient management varies widely. In this setting, rate control or rhythm control could be beneficial in limiting the duration of shock and preventing evolution to multiorgan dysfunction.

Methods and analysis
The Control Atrial Fibrillation in Septic shock (CAFS) study is a binational (French and Belgium), multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three management strategies in patients with NOSVA during septic shock. The expected duration of patient enrolment is 42 months, starting from November 2021. Patients will be randomised to receive either risk control (magnesium and control of risk factors for NOSVA), rate control (risk control and low dose of amiodarone) or rhythm control (risk control and cardioversion using high dose of amiodarone with external electrical shock if NOSVA persists) for 7 days. Patients with a history of SVA, NOSVA lasting more than 48 hours, recent cardiac surgery or a contraindication to amiodarone will not be included. We plan to recruit 240 patients. Patients will be randomised on a 1:1:1 basis and stratified by centre. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality and the duration of septic shock defined as time from randomisation to successful weaning of vasopressors. Secondary outcomes include: individual components of the primary endpoint; arterial lactate clearance at day 3; efficacy at controlling cardiac rhythm at day 7; proportion of patients free from organ dysfunction at day 7; ventricular arrhythmia, conduction disorders, thrombotic events, major bleeding events and acute hepatitis related to amiodarone at day 28; intensive care unit and hospital lengths of stay at day 28.

Ethics and dissemination
The study has been approved by the French (Comité Sud-Ouest et Outre-Mer II, France, registration number 2019-A02624-53) and Belgian (Comité éthique de l’hôpital Erasme, Belgium, registration number CCB B4062023000179) ethics committees. Patients will be included after obtaining signed informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial registration number
NCT04844801.

Annals of Internal Medicine, Ahead of Print.

This study compares hospitalization and mortality outcomes in vaccinated older adults with vs without restricted access to nirmatrelvir-ritonavir in Ontario.

Introduction
Palliative care (PC) improves quality of life (QOL). However, PC is currently delivered ‘too little, too late’ in heart failure (HF). Timely interventions to enable and reach patients with HF and their caregivers, with PC (TIER-HF-PC) is a novel, nurse coach-led model of PC that integrates PC into HF care. We will compare the effectiveness of TIER-HF-PC against usual care for improving patient and caregiver health outcomes. We will also evaluate implementation outcomes (such as care experience) of TIER-HF-PC.

Methods and analysis
In TIER-HF-PC, patients undergo regular distress screening. The intensity of PC treatments will be tiered based on the severity of problems detected. Minimally, all patients will receive PC education resources. Patients with moderate-intensity needs will receive PC health coaching. Patients with high-intensity needs will receive a PC physician consultation, on top of PC health coaching. Patients in usual care are not screened but can be referred to a PC physician based on cardiologist discretion.
We will recruit 240 English- or Mandarin-speaking patients with HF and up to 240 caregivers from 3 sites across 2 cardiac centres. Patients will be randomised in a 1:1 ratio to TIER-HF-PC or usual care. We will use an intention-to-treat approach for data analysis. Our primary outcome is patient QOL on the Kansas City Cardiomyopathy Questionnaire at 24 weeks. Secondary outcomes include patient healthcare utilisation, caregiver QOL and cost-effectiveness. All participants who received PC treatments will receive a service evaluation survey. Additionally, a sample of these participants and their treating healthcare staff will be purposively recruited for in-depth semistructured interviews on their TIER-HF-PC experience. Interviews will be thematically analysed. We will evaluate protocol fidelity through case notes and study process audits.

Ethics and dissemination
This study was approved by the SingHealth Institutional Ethics Review Board—review number: 2024–2213. Results of the study will be disseminated when data analysis is complete.

Trial registration number
NCT06244953.

Background
Immunotherapies targeting the programmed death receptor-1/programmed death ligand-1(PD-1/PD-L1) checkpoint have a major impact on the treatment of both resectable and advanced non-small cell lung cancer (NSCLC). Additional blockade of the T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-receptor may synergistically foster the immune-related response. Several trials are currently investigating the combination of neoadjuvant platinum-based chemotherapy and dual checkpoint inhibition prior to curative surgery. The investigator-initiated NeoTRACK trial (EU CT number: 2022-501322-38-00; ClinicalTrials.gov identifier: NCT05825625; IKF056) aims to evaluate the feasibility and safety of perioperative anti-PD-L1 (by atezolizumab) and anti-TIGIT (by tiragolumab) treatment in combination with chemotherapy in patients with early stage NSCLC.

Methods and analysis
NeoTRACK is an open-label, single-arm, prospective, bicentric phase II trial. Patients with NSCLC in clinical stages II, IIIA and IIIB (only T3N2) will receive two cycles of standard platinum-based chemotherapy in combination with the anti-TIGIT antibody tiragolumab and the anti-PD-L1 antibody atezolizumab, followed by curative surgery. After surgery, patients without pathological complete response (pCR) will receive another two cycles of chemotherapy in combination with tiragolumab and atezolizumab, followed by tiragolumab/atezolizumab maintenance for up to 1 year (maximum 16 cycles). Patients with pCR will only receive dual immunotherapy. All patients will be followed-up for 30 months after the last study treatment. The clinical study will be aligned with a translational research programme to investigate treatment-naïve tumour tissues, surgical specimens and longitudinally collected blood samples. 35 patients are planned for enrolment. Patient recruitment started in August 2023, and treatment of the last patient is estimated to start 2.5 years thereafter.

Discussion
The NeoTRACK trial aims to assess the feasibility and efficacy of combining tiragolumab and atezolizumab as both neoadjuvant and adjuvant therapies in patients with resectable NSCLC. The concept of treatment personalisation based on postoperative pCR is of great clinical interest.

Ethics and dissemination
The trial obtained ethical and regulatory approval in Germany through the Clinical Trials Information System (CTIS, ID: 2022-501322-38-00) and the Paul Ehrlich Institute (PEI, competent authority for approval of clinical trials using medicinal products for human use in Germany, process number: PB00148) on 30 March 2023. A data safety and monitoring board will meet regularly to review ongoing treatment in terms of safety.
Study results will be published in peer-reviewed journals, presented at conferences and in the public registry of CTIS, following trial completion.

Trial registration number
NCT05825625.

Background
Immunotherapies targeting the programmed death receptor-1/programmed death ligand-1(PD-1/PD-L1) checkpoint have a major impact on the treatment of both resectable and advanced non-small cell lung cancer (NSCLC). Additional blockade of the T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-receptor may synergistically foster the immune-related response. Several trials are currently investigating the combination of neoadjuvant platinum-based chemotherapy and dual checkpoint inhibition prior to curative surgery. The investigator-initiated NeoTRACK trial (EU CT number: 2022-501322-38-00; ClinicalTrials.gov identifier: NCT05825625; IKF056) aims to evaluate the feasibility and safety of perioperative anti-PD-L1 (by atezolizumab) and anti-TIGIT (by tiragolumab) treatment in combination with chemotherapy in patients with early stage NSCLC.

Methods and analysis
NeoTRACK is an open-label, single-arm, prospective, bicentric phase II trial. Patients with NSCLC in clinical stages II, IIIA and IIIB (only T3N2) will receive two cycles of standard platinum-based chemotherapy in combination with the anti-TIGIT antibody tiragolumab and the anti-PD-L1 antibody atezolizumab, followed by curative surgery. After surgery, patients without pathological complete response (pCR) will receive another two cycles of chemotherapy in combination with tiragolumab and atezolizumab, followed by tiragolumab/atezolizumab maintenance for up to 1 year (maximum 16 cycles). Patients with pCR will only receive dual immunotherapy. All patients will be followed-up for 30 months after the last study treatment. The clinical study will be aligned with a translational research programme to investigate treatment-naïve tumour tissues, surgical specimens and longitudinally collected blood samples. 35 patients are planned for enrolment. Patient recruitment started in August 2023, and treatment of the last patient is estimated to start 2.5 years thereafter.

Discussion
The NeoTRACK trial aims to assess the feasibility and efficacy of combining tiragolumab and atezolizumab as both neoadjuvant and adjuvant therapies in patients with resectable NSCLC. The concept of treatment personalisation based on postoperative pCR is of great clinical interest.

Ethics and dissemination
The trial obtained ethical and regulatory approval in Germany through the Clinical Trials Information System (CTIS, ID: 2022-501322-38-00) and the Paul Ehrlich Institute (PEI, competent authority for approval of clinical trials using medicinal products for human use in Germany, process number: PB00148) on 30 March 2023. A data safety and monitoring board will meet regularly to review ongoing treatment in terms of safety.
Study results will be published in peer-reviewed journals, presented at conferences and in the public registry of CTIS, following trial completion.

Trial registration number
NCT05825625.

Introduction
Palliative care (PC) improves quality of life (QOL). However, PC is currently delivered ‘too little, too late’ in heart failure (HF). Timely interventions to enable and reach patients with HF and their caregivers, with PC (TIER-HF-PC) is a novel, nurse coach-led model of PC that integrates PC into HF care. We will compare the effectiveness of TIER-HF-PC against usual care for improving patient and caregiver health outcomes. We will also evaluate implementation outcomes (such as care experience) of TIER-HF-PC.

Methods and analysis
In TIER-HF-PC, patients undergo regular distress screening. The intensity of PC treatments will be tiered based on the severity of problems detected. Minimally, all patients will receive PC education resources. Patients with moderate-intensity needs will receive PC health coaching. Patients with high-intensity needs will receive a PC physician consultation, on top of PC health coaching. Patients in usual care are not screened but can be referred to a PC physician based on cardiologist discretion.
We will recruit 240 English- or Mandarin-speaking patients with HF and up to 240 caregivers from 3 sites across 2 cardiac centres. Patients will be randomised in a 1:1 ratio to TIER-HF-PC or usual care. We will use an intention-to-treat approach for data analysis. Our primary outcome is patient QOL on the Kansas City Cardiomyopathy Questionnaire at 24 weeks. Secondary outcomes include patient healthcare utilisation, caregiver QOL and cost-effectiveness. All participants who received PC treatments will receive a service evaluation survey. Additionally, a sample of these participants and their treating healthcare staff will be purposively recruited for in-depth semistructured interviews on their TIER-HF-PC experience. Interviews will be thematically analysed. We will evaluate protocol fidelity through case notes and study process audits.

Ethics and dissemination
This study was approved by the SingHealth Institutional Ethics Review Board—review number: 2024–2213. Results of the study will be disseminated when data analysis is complete.

Trial registration number
NCT06244953.

Introduction
Precision oncology aims to provide individualised treatment recommendations based on patient-specific characteristics. In this rapidly evolving field with increasing numbers of biomarkers and potential therapeutic targets, there is a growing unmet need for evidence guiding these individualised treatment recommendations. The Precision Oncology Program (POP) harnesses real-world data (RWD) and imaging mass cytometry (IMC) to evaluate the feasibility and utility of integrating different data modalities to inform personalised treatment recommendations. This program uses patient-matched clinicogenomic data and spatial single-cell proteomics analysis to support profiling-driven decision-making for patients with cancer at the Molecular Tumor Board.

Methods and analysis
The collaborative POP project recruits patients across all tumour entities and stages at the Comprehensive Cancer Center Zurich (CCCZ). For patients in the POP, a clinically and molecularly matched cohort is identified within the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine clinicogenomic database (CGDB). It assesses whether clinical, genomic and outcome data of the CGDB cohort can inform treatment recommendations. In addition, multiplexed imaging mass cytometry (IMC) is performed in formalin-fixed paraffin-embedded tissue to assess the potential impact of spatial proteomics on personalised treatment decisions. RWD and IMC information is reviewed in the Molecular Tumor Board to assess the potential impact of this information on therapy decisions. However, since this is an observational study, these additional recommendations remain nonprescriptive and will not be forwarded to the treating physician.

Ethics and dissemination
The study is registered at ClinicalTrials.gov (NCT06680726) and approved by the Canton of Zurich Ethics Committee (Project ID: 2022-02289). Project-specific informed consent is obtained from all participants. Deceased patients may also be included. In this case, a signed general consent form must be available. Data privacy is ensured by unique patient numbers for pseudo-anonymised data. Study findings will be disseminated through international peer-reviewed journals, conferences, and direct communication with participants and relevant organisations.

Trial registration number
NCT06680726.

Introduction
Non-specific pain (NSP), defined as pain without a clear pathological cause, is a common presentation in the emergency department (ED). There is no universally accepted analgesic strategy, but non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are often prescribed. However, the established efficacy of NSAIDs for NSP is limited. Additionally, NSAIDs are associated with an increased risk of upper gastrointestinal bleeding, acute kidney injury and cardiovascular events, such as myocardial infarction and stroke. There is increasing evidence supporting the analgesic effects of open-label placebo (OLP), defined as placebo administered to patients without deception, in a broad variety of settings. Accordingly, OLP could be a safer, effective analgesic treatment option for NSP. To our knowledge, this is the first study investigating the feasibility of OLP for NSP in the ED. Therefore, our primary objective is to assess whether OLP is a feasible treatment option in this setting.

Methods and analysis
Patients diagnosed with acute NSP will be prospectively recruited at discharge in the ED at the University Hospital of Basel, Switzerland. Patients treated with pain medication for >7 days prior to ED visit or with chronic pain will be excluded. Patients will be randomised to receive either OLP (intervention) or ibuprofen (control). Rescue medication will be ibuprofen in both groups. Daily online self-assessment will take place during the first 7 days after the baseline visit as well as on day 30. A qualitative interview will be conducted on day 30. The primary outcome is feasibility, consisting of acceptability, adherence to the protocol and patient satisfaction. Clinical outcomes will focus on pain intensity and interference according to the Brief Pain Inventory Short Form as well as adverse events.

Ethics and dissemination
The study protocol has received approval from the ethics committee for Northwestern and central Switzerland (EKNZ; project ID 2024-00089). The results will be disseminated in peer-reviewed journals and at scientific conferences.

Trial registration number
Swiss National Clinical Trials Portal (SNCTP000005852); Clinicaltrial.gov (NCT06408519).

Yang X, He X, Pan D, et al. Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. BMJ Open 2024;14:e091059. doi: 10.1136/bmjopen-2024091059
This article was previously published with an error.
Figure 1 has been updated. During the trial, some participating centres underwent official name changes. The figure now reflects the revised names while maintaining the original study site distribution. These changes neither affect the centres themselves or the conduct of the trial nor the study’s data and conclusions.

A study has found that patients with 1 of 5 acute surgical conditions who traveled longer distances to emergency departments were more likely to present with higher complexity of emergency general surgery disease. The retrospective study, published in JAMA Network Open, provides new evidence supporting travel time as an alternative metric to rurality for policies aiming to improve timely access to care.

Introduction
Chronic diseases place a large burden on health systems globally. While long-term planned care is essential for their management, episodes of deterioration are common. The emergence of rapid access to outpatient care has proliferated in response to increased resource pressures on acute health services. It is anticipated that these new models of care may prevent hospitalisations and reduce the burden on emergency departments. While some evidence supports the clinical effectiveness of these models, little is known about the core components and key attributes of these services. This paper outlines the protocol of a theory-driven, pragmatic process evaluation embedded within a new rapid-access outpatient service for chronic disease in South East Queensland, Australia.

Methods and analysis
This mixed-methods process evaluation will be conducted across three phases: (1) context assessment to identify programme characteristics and core components; (2) evaluation of key service processes and development of service improvement strategies and (3) sustainability assessment, with a focus on programme embedding and the resources associated with service evaluation. Each phase will be guided using implementation science frameworks and/or theory. Participants will include service consumers, service delivery staff, implementation leaders and decision-makers and wider system referrers. Professional stakeholders will be recruited through a direct invitation to participate (using purposeful sampling methods) and will be engaged in interviews at 1–3 data collection time points. Service consumers will be recruited through direct advertisement to participate in interviews. Administrative and clinical data collections will be retrospectively analysed with descriptive and inferential methods and triangulated with qualitative data to yield primary and secondary outcomes.

Ethics and dissemination
Ethical clearance has been obtained from the West Moreton Hospital and Health Service Human Research Ethics Committee. The planned dissemination of results will occur through conferences, abstracts and publications.

Trial registration number
Australia and New Zealand Clinical Trials Registry (ANZCTR Trial ID: ACTRN12624000757516).

Introduction
Children and young people (CYP) from priority populations in Australia have inequities in accessing healthcare, health outcomes and opportunities to lead healthy lives. Priority populations include CYP who are Aboriginal and/or Torres Strait Islander, culturally and linguistically diverse (born in a country where English is not an official language and/or speak a language other than English at home), with experience of being a refugee or asylum seeker, living in out-of-home care or with a disability. Providing Enhanced Access to Child Health Services (PEACH) is an organisation-wide quality improvement project that aims to achieve equivalent health outcomes in CYP from priority populations compared with their non-priority population peers.

Methods and analysis
PEACH creates an equity-focused learning health system using electronic medical record (eMR) patient data and qualitative methodology exploring staff and service user experiences. Five priority population advisory groups, consisting of staff and priority population service users, guide the research at the Sydney Children’s Hospitals Network (SCHN), Australia’s largest tertiary paediatric health service. Interviews, surveys and co-design workshops with service users (CYP and/or their parent/carer) and staff describe existing health inequities and inform the design and implementation of interventions to improve identification, provision of earlier and supported access to services and effect cultural change. The impact of PEACH on reducing inequity in care and outcomes will be measured by comparing data during and after implementation (2020–2027) with baseline data before implementation (2015–2019) and with national controls, controlling for potential confounding factors. Health access and outcome measures, including emergency and preventable hospitalisations, critical care admission, discharge against medical advice, readmission and extended length of stay, will be analysed and drawn into dashboards, driving continuous learning and improvement.

Ethics and dissemination
The SCHN Human Research Ethics Committee (2022/ETH00145) and Aboriginal Health and Medical Research Council (1920/22) have granted ethics approval. Research findings will be shared with service users, staff advisory groups and the wider children’s healthcare sector through presentations, conferences and peer-reviewed journals.

Introduction
In overdose, a larger proportion of paracetamol (acetaminophen) is converted in the liver to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Glutathione (GSH) is the endogenous antioxidant that protects cells from NAPQI-induced injury. In overdose, GSH stores may become depleted, leaving NAPQI free to produce liver damage. N-Acetylcysteine (NAC) helps prevent paracetamol toxicity by replenishing liver GSH. This protective effect of NAC produces specific metabolites in the circulation. Currently, regardless of the paracetamol dose ingested, patients in the UK receive a dose of NAC based only on their weight. Basic pharmacology, mathematical modelling and observational studies suggest that this dose may be insufficient in some patients (particularly those taking a large overdose).

Methods and analysis
A multicentre trial, taking place across several hospitals in Scotland, UK, within Emergency Departments and Acute Medical Units. Recruitment commenced on 19 February 2024 and is anticipated to run for approximately 2 years. This is a three-group dose-finding trial, in which participants are assigned in a 1:1:1 ratio to either Standard NAC (300 mg/kg) or higher doses of 450 mg/kg (Group 1) and 600 mg/kg (Group 2). The primary outcome is the proportion of paracetamol metabolites in the circulation that are directly produced by GSH/NAC detoxification of NAPQI. A higher proportion of these metabolites will indicate that the additional NAC is reducing the amount of toxic paracetamol metabolites in the body. The study will first test the primary outcome on the HiSNAP Group 2 against Standard NAC; only if that is significant will HiSNAP Group 1 be tested against Standard NAC.

Ethics and dissemination
The HiSNAP trial has been approved by the East Midlands (Derby) Research Ethics Committee (reference 23/EM/0129), NHS Lothian Research and Development Department, and the MHRA. Results will be disseminated by peer-reviewed publication, conferences and linked on isrctn.com.

Trial registration number
ISRCTN17516192.

New England Journal of Medicine, Ahead of Print.

Objectives
To examine the intersectional associations between migration experiences and use of health and sex work community-based services among women sex workers.

Design
Data were drawn from An Evaluation of Sex Workers Health Access, a community-based cohort of sex workers from September 2014 to February 2022. Bivariate and multivariable regression with generalised estimating equations (GEEs) using interaction terms was used to separately model associations between intersectional aspects of the migration experience (citizenship, English fluency and Asian identity) and service access outcomes.

Setting
Diverse community-based sex work venues in Metro Vancouver, Canada.

Participants
652 cis and trans women sex workers, with 149 (22.8%) being immigrants/migrants born outside of Canada (n=149).

Primary outcome measures
(1) Accessing health services when needed and (2) utilisation of sex work community-based services.

Results
In separate adjusted multivariable GEE models, we found significantly reduced odds of accessing health services when needed for women without Canadian citizenship and with limited English fluency, as well as those lacking Canadian citizenship but speaking fluently. Significantly reduced odds of accessing health services were also found among sex workers without Canadian citizenship and who identified as Asian. Regarding using sex work community-based services, women sex workers lacking Canadian citizenship and with limited English fluency, and those who were Asian and lacked Canadian citizenship, had low odds of using sex work community-based services.

Conclusions
Findings show a gradient in the relationship between intersectional experiences of lack of citizenship, limited English fluency and Asian identity on sex workers’ access to health services and sex work community-based services. Culturally responsive and language-tailored services that attend to and address these intersecting forms of structural marginalisation, along with the full decriminalisation of all aspects of sex work, and the removal of punitive sex work-related immigration policies, are recommended.