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Evaluating the diagnostic accuracy of WHO-recommended treatment decision algorithms for childhood tuberculosis using an individual person dataset: a study protocol

Por: Olbrich · L. · Larsson · L. · Dodd · P. · Palmer · M. · Nguyen · M. H. T. N. · dElbee · M. · Hesseling · A. C. · Heinrich · N. · Zar · H. J. · Ntinginya · N. E. · Khosa · C. · Nliwasa · M. · Verghese · V. · Bonnet · M. · Wobudeya · E. · Nduna · B. · Moh · R. · Mwanga · J. · Mustapha · A. · B
Introduction

In 2022, the WHO conditionally recommended the use of treatment decision algorithms (TDAs) for treatment decision-making in children

Methods and analysis

Within the Decide-TB project (PACT ID: PACTR202407866544155, 23 July 2024), we aim to generate an individual-participant dataset (IPD) from prospective TB diagnostic accuracy cohorts (RaPaed-TB, UMOYA and two cohorts from TB-Speed). Using the IPD, we aim to: (1) assess the diagnostic accuracy of published TDAs using a set of consensus case definitions produced by the National Institute of Health as reference standard (confirmed and unconfirmed vs unlikely TB); (2) evaluate the added value of novel tools (including biomarkers and artificial intelligence-interpreted radiology) in the existing TDAs; (3) generate an artificial population, modelling the target population of children eligible for WHO-endorsed TDAs presenting at primary and secondary healthcare levels and assess the diagnostic accuracy of published TDAs and (4) identify clinical predictors of radiological disease severity in children from the study population of children with presumptive TB.

Ethics and dissemination

This study will externally validate the first data-driven WHO TDAs in a large, well-characterised and diverse paediatric IPD derived from four large paediatric cohorts of children investigated for TB. The study has received ethical clearance for sharing secondary deidentified data from the ethics committees of the parent studies (RaPaed-TB, UMOYA and TB Speed) and as the aims of this study were part of the parent studies’ protocols, a separate approval was not necessary. Study findings will be published in peer-reviewed journals and disseminated at local, regional and international scientific meetings and conferences. This database will serve as a catalyst for the assessment of the inclusion of novel tools and the generation of an artificial population to simulate the impact of novel diagnostic pathways for TB in children at lower levels of healthcare. TDAs have the potential to close the diagnostic gap in childhood TB. Further finetuning of the currently available algorithms will facilitate this and improve access to care.

Global therapeutic mobilities and cancer: a scoping review

Por: Schantz · C. · Boisson · S. · Prost-Lancon · L. · Bonnet · E. · Dancoisne · A. · Baron · M. · Bochaton · A. · The SENOVIE Group · Schantz · Aboubakar · Baron · Guetz · Gosselin · Petitet · Larmarange · Niangaly · Rath · Teixeira · Traore · Agbodande · Agbodjavou · Bochaton · Boisson
Introduction

Research on therapeutic mobility is abundant but the field of cancer has not yet been investigated thoroughly. This scoping review aims to examine the existing evidence on global therapeutic mobility and cancer, providing a comprehensive overview of the subject.

Methods

We conducted a scoping review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodological guidelines. We developed a comprehensive search strategy and discussed it with the research team. We searched for peer-reviewed papers on Medline, Embase, ERIC and American Psychological Association via the Dialogue interface and Google Scholar and CAIRN bibliographic database for peer-reviewed articles. We also included grey literature, such as unpublished work and relevant reports from Érudit. We considered studies that employed quantitative or qualitative methods.

Results

Among the 1615 references initially selected, 767 duplicates were excluded. Then, 849 studies were screened on title and abstract and 800 were excluded as they did not meet inclusion criteria. 49 studies were fully screened and 21 were excluded as they did not meet inclusion criteria based on full-text assessment. Ultimately, 28 references were included in the data synthesis. This scoping review has shown that publications on therapeutic mobilities have multiplied in recent years, with a turning point in 2019. A range of academic disciplines and research methodologies are currently employed to describe them. A significant proportion of fieldwork is concentrated in Asia, Africa, Europe and North America. Despite the heterogeneity of the approaches and fields, there are certain common features that emerge: first, the decision to migrate for healthcare is primarily made by the patient themselves and is perceived by them as being non-choice; second, the family plays a central role at all stages of the migration; and third, the migration has a catastrophic impact in terms of social and financial burden.

Conclusion

In conclusion, this scoping review highlights the underexplored relationship between global therapeutic mobility and cancer, emphasising the need for increased research efforts to understand the global dynamics of cancer care mobility.

Rationale and design of 'discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM): study protocol of a randomised non-inferiority clinical trial

Por: Aebi · P. S. · Adam · L. · Haller · M. · Bardoczi · J. B. · Gencer · B. · Bonnet · F. · Beer · J.-H. · Carballo · S. · Christ-Crain · M. · Feller · M. · Gabutti · L. · Haynes · A. G. · Moutzouri · E. · Chocano-Bedoya · P. O. · Bassetti · S. · Escher · R. · Egger · M. · Poortvliet · R. K.
Introduction

Statins are among the most widely used drugs. While they are effective for primary and secondary prevention of cardiovascular (CV) disease in middle-aged subjects, their benefits for prevention in older adults (aged ≥70 years) without CV disease are uncertain, particularly for those with multimorbidity. Statin side effects and drug interactions are common in older patients and may negatively impact quality of life. To date, the only randomised controlled trial (RCT) investigating statin discontinuation in older adults has demonstrated no difference in survival but did note a small improvement in quality of life for those who discontinued statins. However, this trial exclusively enrolled patients with a life expectancy

Methods and analysis

This study is a multicentre, randomised, non-inferiority trial conducted in both inpatient and outpatient settings in Switzerland, France and the Netherlands, targeting patients using statins for primary prevention. 1800 participants are randomly assigned 1:1 to either discontinue (intervention arm) or continue (control arm) statin therapy. The primary objective is to compare the primary composite endpoint of major CV events (non-fatal myocardial infarction or non-fatal ischaemic stroke) and all-cause death between the control and intervention groups over a follow-up duration of up to 48 months. We hypothesise that discontinuing statins does not result in shorter event-free survival, with a non-inferiority margin set at 5.2 weeks over a 2-year observation period. Secondary objectives are to compare patient-centred outcomes (health-related quality of life, muscle pain symptoms, falls and sarcopenia) and all-cause death, non-CV death, major CV events and coronary and peripheral artery revascularisation. The study is open-labelled, with blinded outcome adjudication of the primary endpoints.

Ethics and dissemination

The trial protocol has received approval from the local ethics committees in Switzerland, France and the Netherlands. Results will be published in a peer-reviewed journal.

Trial registration number

Clinicaltrials.gov: NCT05178420; BASEC (Swiss Ethics Commission): 2021-01513; FOPH (Swiss national portal): SNCTP000005172; Netherlands Trial Register: NL83907.058.23; France Trial Register: 22.04747.000158– IDRCB 2022-A02481-42.

Risk, rate or rhythm control for new onset supraventricular arrhythmia during septic shock: protocol for the CAFS multicentre, parallel-group, open-label trial

Por: Labbe · V. · Desnos · C. · Preau · S. · Doyen · D. · Contou · D. · Bagate · F. · Souweine · B. · Pey · V. · Bertrand · P.-M. · Müller · G. · Boissier · F. · Asfar · P. · Bonnet · N. · Joffre · J. · Sy · O. · Dres · M. · Annoni · F. · Monnet · X. · Carreira · S. · Vivier · E. · Serck · N. · Wia
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.

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