Abatacept versus tocilizumab for the treatment of rheumatoid arthritis in TNF inhibitor inadequate responders: study protocol of the SUNSTAR randomised controlled open-label superiority trial

Introduction
Biological disease modifying antirheumatic drugs (bDMARDs) have a central role in the treatment of rheumatoid arthritis (RA). Tumour necrosis factor inhibitors (TNFis) are commonly used as first-line agents, while non-TNFis (tocilizumab, abatacept and rituximab) have shown to be non-inferior to TNFis in head-to-head trials. In case of TNFi inadequate response, using other mechanisms of action provides a better response than using an alternate TNFi. Which non-TNFi bDMARD administered subcutaneously to allow for ambulatory management to choose in case of first line TNFi inadequate response has not been tested in a randomised clinical trial, while observational data support a potential superiority of tocilizumab over abatacept.

Methods and analysis
The SUNSTAR (SUbcutaNeouS Tocilizumab vs Abatacept in TNF Alpha inadequate responders for the treatment of Rheumatoid arthritis) study is a 52-week prospective, randomised, multicentre, open-label, superiority phase IV trial comparing subcutaneous tocilizumab with abatacept in a 1:1 ratio. Patients with active RA (Disease Activity Score-erythrocyte sedimentation rate >3.2 and Clinical Disease Activity Index (CDAI) >10) and with inadequate 3-month response to a first or second TNFi are included in 25 centres in France. The primary outcome is the CDAI improvement at week 24. Intention-to-treat analysis will be applied primarily. The secondary outcome is a composite outcome of the percentage of responders defined as a CDAI

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Routine testing for group B streptococcus in pregnancy: protocol for a UK cluster randomised trial (GBS3)

Introduction
It is unclear whether routine testing of women for group B streptococcus (GBS) colonisation either in late pregnancy or during labour reduces early-onset neonatal sepsis, compared with a risk factor-based strategy.

Methods and analysis
Cluster randomised trial.

Sites and participants
320 000 women from up to 80 hospital maternity units.

Strategies
Sites will be randomised 1:1 to a routine testing strategy or the risk factor-based strategy, using a web-based minimisation algorithm. A second-level randomisation allocates routine testing sites to either antenatal enriched culture medium testing or intrapartum rapid testing. Intrapartum antibiotic prophylaxis will be offered if a test is positive for GBS, or if a maternal risk factor for early-onset GBS infection in her baby is identified before or during labour. Economic and acceptability evaluations will be embedded within the trial design.

Outcomes
The primary outcome is all-cause early (

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Poetry and Treatment Tolerability

An important aspect of caring for patients with complex chronic illness, especially older adults with cancer, is understanding how treatment is tolerated. Yet barriers to seeking this information are many, including the debilitation caused by not only illness but also the adverse effects of treatment itself, which can effectively silence patients. In “Treatment Tolerability,” poetry becomes a vehicle for addressing these challenges, and imagining what patients may experience when receiving treatment (in this case, multiple transfusions). Immediately noticeable is the lack of capitalization and punctuation throughout the poem, which suggests the subordination of patients to the imperatives of urgent treatment in the quest for a cure. Adverse effects, such as confusion and weakness, are then conveyed by the haphazard rhyming in the poem; breathlessness, perhaps, is felt in the short, enjambed lines. Even the vague nursery rhyme feel of the poem seems a caution against how clinicians might infantilize and speak down to patients when attempting to assess treatment tolerability. That the poem’s speaker is not the patient but an observer seems to underscore the risk, even with the best of intentions, of supplanting the patient’s voice with our own. Finally, the speaker’s recognition of the inescapability of these concerns, and the frustration, shared by clinicians, that often accompanies them, are deftly expressed in the searching lines, “blindfolded in a fog of pain/covering everything/with a god-like fabric/because no mercy/is bright enough to pass/this fatigue onto another.”

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Global prevalence of chronic kidney disease and associated risk factors in children and adolescents: protocol for a systematic review and meta-analysis

Introduction
While chronic kidney disease (CKD) is well characterised in adults, less is known about the prevalence of CKD in children and adolescents, where it is rare and associated with unique characteristics and implications for long-term health outcomes. This study protocol outlines a systematic review to assess the global prevalence of CKD in children and adolescents along with causes and associated risk factors. This is warranted to better characterise prevalence and to identify at-risk groups that would benefit from screening efforts. We will explore the risk and burden of CKD and its variations by sociodemographic characteristics (age group, race, sex/gender) and geographical regions (country, International Society of Nephrology region and income groups based on World Bank country classifications).

Methods and analysis
We will conduct a systematic review of studies reporting on the prevalence of CKD in children and adolescents following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 (PRISMA-P-2015) and the PRISMA 2020 methodological guidelines (PRISMA 2020). Searches will be undertaken in the following databases with the date range from 2000 to date: Ovid MEDLINE, Ovid Embase, CINAHL, Cochrane Library, ProQuest Dissertations & Theses Citation Index (via Clarivate), Web of Science Core Collection, Google Scholar and grey literature sites (registries, government reports) to identify studies that report on the prevalence of CKD in children and adolescents from ages 0 to 18. The primary outcome will be the global prevalence of CKD in children and adolescents. Secondary outcomes will include the causes of and risk factors for CKD, and examining differences and temporal trends in CKD prevalence across countries, geographical regions, income levels and sociodemographic characteristics.

Ethics and dissemination
No direct involvement with patient data will be used in this systematic review, as data will be obtained from previously published reports. Ethical approval is therefore not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences.

PROSPERO registration number
CRD42024547467.

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Exploring facilitators and barriers in the financial model of hospitals: a qualitative case study on prehabilitation from the Netherlands

Objectives
To explore facilitators and barriers in the financial model of hospitals when a change in a care pathway is implemented.

Design
A qualitative research reported according to the Consolidated Criteria for Reporting Qualitative Research.

Setting
Five hospitals in the Netherlands, between February and September 2023.

Participants
28 interviewees with 7 different stakeholders: (director of) healthcare procurement, contracting manager, financial, business or project manager, physical therapist, board of Medical Consultant Group and surgeon.

Results
The absence of permanent funding in the hospital reimbursement model and the allocation of available resources in the internal hospital distribution model are the two most important barriers when implementing prehabilitation for patients with colorectal cancer. The main facilitator was found to be the internal provision of spare budget. Lump sum agreements are the preferred contract type because they may facilitate internal substitution of budgets according to need. Bundling primary and hospital care funding is recommended to overcome barriers in the financial model. Activity-based budgeting is the preferred budgeting method because budgets can be adjusted over time according to costs. Cost reduction can only be achieved when prehabilitation is offered to more patients. In addition to an appropriate financial model, preconditions like the involvement of a medical specialist and sense of urgency in the organisation should also be arranged.

Conclusions
The financial model of hospitals may affect the implementation of changes in care pathways. Despite barriers in both the reimbursement and the distribution model, it is possible to facilitate this transformation.

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Implementing best practice for peripheral intravenous cannula use in Australian emergency departments: a stepped-wedge cluster-controlled trial and health economic analysis protocol

Introduction
Over one billion adults attend emergency departments (EDs) internationally every year, including 6.6 million in Australia. Up to half of these patients have a peripheral intravenous catheter (PIVC) inserted. Although healthcare workers believe that placing a cannula is helpful (‘just in case’), PIVCs often remain idle. PIVC insertion is painful for patients, takes clinicians’ attention away from other care, has adverse outcomes and causes major economic and environmental burden. Our aim is to codesign an implementation toolkit to reduce unnecessary PIVC insertions and improve other national quality indicators using an implementation science framework.

Methods and analysis
A stepped-wedge cluster-controlled trial will be conducted in nine ED sites (clusters) across Australia. The interventions will be codesigned with and adapted to sites based on local context. The interventions are evidence-based multimodal intervention (MMI) and aligned to the 2021 Australian Commission for Safety and Quality in Health Care National PIVC Clinical Care Standard. The Consolidated Framework for Implementation Research and Learning Health System will be used to guide implementation. Interventions will be phased across three steps (three sites per step), and each site will collect control and postintervention data using mainly routinely collected clinical data. Each site will be allocated to receive the intervention at one of three study steps. Implementation strategies will tailor broad clinician and consumer engagement, policy changes, education, audit and feedback and clinical champions, along with environment and equipment changes, to each site. The primary objective is to reduce the proportion of adult patients who have a PIVC inserted by 10%. We will evaluate the clinical, implementation and cost-effectiveness of the intervention.
Study findings will be used to conduct a health economic analysis, develop an implementation toolkit and inform a sustainable roadmap for national roll-out. This will meet the needs of a diverse range of EDs nationally and internationally.

Ethics and dissemination
The protocol was approved by the Monash Health Human Research Ethics Committee (HREC Reference Number: HREC/100808/MonH-2023-390692(v3)). The outcomes of this trial will be disseminated through peer-reviewed publications, conference presentations and communication with study partners and stakeholders including professional colleges and the Australian Commission for Safety and Quality in Health Care.

Trial registration number
Australian New Zealand Clinical Trials Registry registration number: ACTRN12623001248651. Date of registration: 1 December 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386256&showOriginal=true&isReview=true

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Gender and age disparities in cardiac immune-related adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FAERS database

Objectives
The cardiotoxicity of immune checkpoint inhibitors (ICIs) has garnered significant clinical attention due to its high mortality rate. However, limited clinical research and inconsistent results have hindered a comprehensive understanding of this issue. This study seeks to elucidate gender and age differences in cardiac-related adverse reactions, aiming to offer scientific evidence to inform clinical practice.

Design
A retrospective pharmacovigilance study.

Setting
Based on the reports of ICIs in the FDA Adverse Event Reporting System database from 2003–2023, we conducted a disproportionality analysis to identify cardiac immune-related adverse events (irAEs) and explored the correlation of age and gender with these adverse events.

Main outcome measures
The main cardiac irAEs were defined by four preferred terms: myocarditis, atrial fibrillation, cardiac failure and pericardial effusion. Both the proportional reporting ratio (PRR) and reporting odds ratio (ROR) are frequency methods. Data mining was performed using the PRR method, which assesses the relative risk of adverse drug reactions by comparing the frequency of reports associating a specific drug with a particular adverse reaction to the frequency of reports linking any drug to the same reaction. A higher PRR indicates a more robust adverse event signal, suggesting a stronger statistical association between the drug of interest and the target adverse event. In the research process, we primarily used the ROR and PRR from disproportionality analysis to screen for cardiac irAEs, while also elucidating the correlation between these reactions and factors such as age and gender.

Results
A total of 2033 adverse events were retrieved, and myocarditis was the most common cardiac irAEs. Gender disparities exist in the incidence of various adverse reactions to the same medication. Female patients need to be particularly vigilant for cardiac adverse events when taking atezolizumab, and male patients should be especially cautious for cardiac adverse events when using ipilimumab. Furthermore, ipilimumab produced a positive signal for pericardial effusion in the elderly group but not in the younger group, suggesting that elderly patients may be more susceptible to adverse reactions. Therefore, increased vigilance and careful monitoring are warranted during clinical administration of this medication to elderly patients.

Conclusion
Our study highlights the gender and age differences in cardiac adverse events with ICIs, providing valuable insights for clinical application.

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