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Linezolid in addition to standard antibiotic treatment for Staphylococcus aureus bacteraemia: study protocol for a randomised, placebo-controlled trial

Por: Rose · N. · Bernasconi · N. S. · Schumacher · M. · Werlen · L. · Büchel · D. · Weisser · M. · Vogt · S. B. · Wehrle-Wieland · E. · Conen · A. · Thurnheer · M. C. · Martin · Y. · Birrer · M. · Bongiovanni · M. · Albrich · W. C. · Karrer · U. · Schibli · A. · Harbarth · S. · Papadimitrio
Introduction

Staphylococcus aureus (S. aureus) bacteraemia is a common and severe infection. With mortality rates ranging from 20–30% and long-term impairments in over a third of survivors, better treatments are urgently needed. Linezolid, a well-established treatment for pneumonia and complicated skin infections, has been shown in preclinical studies to strongly suppress S. aureus virulence factors critical to bacterial persistence and tissue damage. Hence, we aim to investigate whether the addition of linezolid to standard therapy in patients with S. aureus bacteraemia leads to an overall improvement in patient-relevant outcomes.

Methods and analysis

We will conduct a two-arm, parallel-group, multicentre, randomised controlled trial (Linezolid Plus Standard of Care) in 12 hospitals in Switzerland with blinded treating physicians, patients and outcome assessors. Hospitalised patients aged ≥18 years with S. aureus bacteraemia will be eligible. Patients will receive standard antibiotic treatment as prescribed by the treating physician. Within 72 hours of collection of the blood sample yielding the first positive blood culture, patients will be enrolled and randomised 1:1 to receive either adjunctive linezolid (600 mg orally two times per day for 5 days) or placebo. To determine patient-relevant outcomes, we implemented a comprehensive patient-representative consultation process. Consequently, we will use the desirability of outcome ranking (DOOR) established for S. aureus bacteraemia as the primary outcome at 90 days. The hierarchical composite DOOR outcome includes the following four components, ranked from most to least important: (1) survival, (2) return to level of function before S. aureus infection, (3) complications leading to treatment changes and serious adverse reactions; and (4) hospital length of stay. This approach will allow us to analyse the win ratio, that is, whether patients receiving linezolid have a better DOOR rank compared to patients in the placebo group. We calculated a target sample size of 606 patients providing 90% power at a two-sided significance level of 0.05.

Ethics and dissemination

Ethical approval was received from the Ethics committee for Northern and Central Switzerland (BASEC number 2025-00655). Eligible patients will be informed about the study by the local study team and asked for written consent if they wish to participate. For patients unable to provide informed consent, an appropriate substitute (ie, a close relative or a physician not involved in the research project) may make decisions based on the presumed wishes and the best interest of the patient. The patient’s own consent will be obtained as soon as their condition permits. Results will be published in peer-reviewed journals and in laymen's terms through various channels (social media, Swiss national portal HumRes).

Trial registration number

NCT06958835.

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Disability severity transitions in the community-dwelling Swiss ageing population: secondary analysis of the Swiss version of the Survey of Health, Ageing and Retirement in Europe (SHARE) using multistate models

Por: Hodel · J. · Rothacher · Y. · Moreira · B. · Fellinghauer · C. · Pacheco Barzallo · D. · Weisstanner · D. · Ehrmann · C. · Sabariego · C.
Objective

To describe disability severity transitions in the ageing population in Switzerland using an overall functioning score to define four disability severity states (no, mild, moderate and severe) and death, and to investigate the association of multimorbidity and further predictors with these transitions.

Design

Secondary analysis of the Swiss version of the Survey of Health, Ageing and Retirement in Europe (SHARE).

Setting

Switzerland.

Participants

Community-dwelling population aged 50+ with at least two interviews in SHARE (N=3505).

Interventions

Not applicable.

Main outcome measures and methods

Primary outcome measures are the disability severity as assessed by a previously developed overall functioning score, and death status as assessed by the SHARE end-of-life interview. Transition analysis between disability severity states and death was conducted using multistate Markov models. The association between predictor variables and transition intensities was quantified using the proportional hazards assumption. Two distinct operationalisations of multimorbidity (count, burden) were used and analysed according to two separate models (A, B).

Results

The findings for both models were similar: Estimated HRs for transition intensities suggest that being multimorbid or having a higher disease burden score increases the risk of transitioning to higher disability severity states and death for most transitions (HRs between 0.90 and 2.34 for model A compared with not being multimorbid; HRs between 0.95 and 1.46 for model B for a one-point increase in the disease burden score). In addition, most transitions to higher disability severity states and death are more likely for higher age (HRs between 1.00 and 1.14 for model A, and between 1.00 and 1.15 for model B for a 1 year increase in age), and transitions to death are less likely for women, compared with men (HRs between 0.34 and 0.88 for model A, and between 0.38 and 0.71 for model B).

Conclusions

This study is a first attempt to understand disability severity transitions in the older population in Switzerland. Although we believe that such an approach is suitable to inform resource allocation to LTC, rehabilitation and prevention, more detailed information on contextual factors will be important to consider for future research. Moreover, our study contributes to the discussion on how to operationalise multimorbidity in healthy ageing research.

Factors Associated with Retention in Routine Well-Care Visits Among Children of Adolescent Mothers Living With and Without HIV: A Community-Based Study in the Eastern Cape, South Africa

Por: Wittesaele · C. · Toska · E. · Cluver · L. D. · Weiss · H. A. · Doyle · A. M.
Objective

To describe well-care visit attendance among children of adolescent mothers living with HIV and HIV-negative adolescent mothers and identify factors associated with optimal retention in the well-care visit schedule up to 18 months.

Design, setting, participants

Cross-sectional data were used from a community-based observational cohort study of adolescent mothers (10–19 years; n=481) and their children (≥19 months old; n=502) in the Eastern Cape, South Africa.

Outcome

Optimal well-care visit retention up to 18 months was defined as attending visits within 4 weeks of the recommended child age, attending the 18-month visit and missing no more than one scheduled visit.

Results

Attendance was highest at the 6-week visit (88.4%; 95% confidence interval (CI) 85.6% to 91.3%) and lowest at the 18-month visit (58.0%, 95% CI 53.6% to 62.3%). About one-third (36.1%; 95% CI 31.8% to 40.3%) of children were retained to 18 months. Retention was highest among children living in rural vs urban areas (adjusted odds ratio (aOR)=2.01, 95% CI 1.32 to 3.06), those born to mothers whose highest education at pregnancy was secondary versus primary school (aOR=2.73, 95% CI 1.60 to 4.65), born via caesarean section vs vaginal birth (aOR=1.65, 95% CI 1.05 to 2.60) and living closer to the clinic (aOR=0.52, 95% CI 0.28 to 0.96 for long vs short distance). There was weak evidence that retention was lower among children of mothers living with HIV (aOR=0.64, 95% CI 0.40 to 1.02) and higher among food-secure children (aOR=2.18, 95% CI 0.96 to 4.96) and those receiving the child support grant (aOR=1.71, 95% CI 0.92 to 3.16).

Conclusions

Universal interventions are needed for retention beyond the neonatal period for children of adolescent mothers living with HIV and HIV-negative adolescent mothers. Interventions must address structural barriers, especially for adolescent mothers with primary education and in urban areas. Future research should examine the underlying mechanisms linking mode of delivery with well-care retention.

Evaluating AI-based comprehensive clinical decision support for sepsis and ARDS: protocol for a Clinician Turing Test

Por: Angeli Gazola · A. · Bishop · N. S. · Schmid · B. E. · Pirracchio · R. · Valley · T. S. · Bhavani · S. V. · Krutsinger · D. C. · Giannini · H. M. · Lu · Y. · Ungar · L. H. · Meyer · N. J. · Kerlin · M. P. · Weissman · G. E.
Introduction

Few artificial intelligence (AI) clinical decision support systems (CDSSs) are ever evaluated in practice. Although some signal of clinical effectiveness may be needed to justify AI deployment and testing, such data are typically unavailable in early-stage research. This conundrum is especially relevant in the intensive care unit (ICU), where conditions like sepsis and acute respiratory distress syndrome (ARDS) require high-stakes decisions. Our group developed the AI ventilator assistant (AVA), a novel AI CDSS for patients with sepsis ARDS receiving invasive mechanical ventilation. But the promising results of predictive performance estimates are not sufficient to assess AVA’s clinical safety and appropriateness prior to future evaluation and deployment. Therefore, we propose a Clinician Turing Test as a novel validation approach to determine whether clinicians can distinguish AVA-generated treatment recommendations from those enacted by real human clinicians. If AVA’s recommendations are consistently indistinguishable from those of real clinicians, thereby ‘passing’ this Turing test, this would provide a strong preclinical signal of safety and appropriateness.

Methods and analysis

This multisite, randomised, electronic, vignette-based Phase 1b study will use a Clinician Turing Test design. We aim to recruit 350 critical care clinicians, including physicians and advanced practice providers from six US hospitals. Participants will review nine clinical vignettes of patients with sepsis and ARDS derived from the Molecular Epidemiology of Severe Sepsis in the ICU cohort and an associated profile of a suggested treatment plan. For each participant–vignette combination, the source of the treatment profile will be randomly assigned (AI-generated by AVA vs the actually enacted treatment from real human clinicians) in a 1:1 allocation. The primary endpoint is the participants’ accuracy in identifying whether a treatment profile was AI-generated or human-generated, assessed using equivalence testing through a mixed-effects logistic regression model with random effects for participants and vignettes. Secondarily, a fitted binary classifier will assess discrimination ability using the C-statistic. Secondary endpoints include clinicians’ perceptions of the safety and appropriateness of the treatment profiles, confidence in distinguishing AI-generated and human-generated recommendations, interest in AI CDSSs for sepsis and ventilator management and the time to complete the survey. This novel Phase 1b design provides preliminary but essential information about an AI CDSS’s clinical appropriateness without the risk or cost of actual deployment, thereby informing decisions about future clinical implementation and evaluation in real clinical environments.

Ethics and dissemination

This protocol was approved by the Institutional Review Board of the University of Pennsylvania (Protocol #858201). Results are expected in 2026 and will be submitted for publication in peer-reviewed journals and presented at scientific conferences.

Trial registration number

NCT07025096.

Do professional experience and qualification influence knowledge about law concerning informed consent and end-of-life decisions? A quantitative online survey among German intensive care physicians

Por: Schumann · C. · Wachter · M. · Eslauer · E. · Angeli · R. · Girrbach · F. · Weiss · M. · Friedrich · S. · Simon · P. · Heller · A. R.
Background

Recently, legal questions have increasingly arisen in intensive care medicine (ICM), especially when it comes to end-of-life decisions. Still, for Europe, there is not much evidence about doctors’ situational legal knowledge and legal education during medical studies and further qualification. The present study was initiated to analyse these hitherto unexplored aspects in Germany.

Design

A quantitative online survey has been performed among German intensive care physicians. The voluntary participants of the anonymous online survey were asked to answer legal questions related to end-of-life policies, informed consent, surrogate decision making or advance directives. We tested pure factual knowledge in five questions. The other five questions tested situational knowledge using case vignettes. Every question could be answered with ‘yes’, ‘no’ or ‘do not know’. Furthermore, the participants were asked to assess their subjective certainty on a Likert scale and to provide information about their professional experience (PE) and qualification.

Setting

All members of the two German professional societies for anaesthesiology who work in ICM were asked to take part in the survey.

Participants

952 completed questionnaires were analysed. 86% of the participants were specialists, and 56% held the additional qualification in ICM. 78% had more than 10 years of general clinical experience, and 62% had more than 5 years of experience in ICM.

Results

On average, the participants answered the five facts–questions in 90.8% correctly. However, only 73.6% of the five case vignettes were answered correctly. Specialists, physicians with a lot of PE or physicians holding the additional qualification in ICM did not perform better than assistants or physicians with little PE.

Conclusion

German intensive care physicians have relevant gaps regarding situational legal knowledge, which are independent of their PE or qualification and persist. This may be due to difficulties in interpretation and implementation of law. Since these knowledge gaps can lead to liability and criminal prosecution, these gaps should be closed through awareness-raising and continuous education.

Development of intersectoral medical care for patients with 'chronic critical illness: protocol for a telemedicine interventional study with a pre-post design in out-of-hospital intensive care facilities (E=MC{superscript 2})

Por: Edel · A. · Jöbges · S. · Weiss · B. · Paul · N. · Lyall · M. L. · Hoffmann · C. · Schüürhuis · S. · Piper · S. K. K. · Konietschke · F. · Berger · E. · Busse · R. · Marschall · U. · Kraufmann · B. · Witzenrath · M. · Eckardt · K.-U. · Spies · C.
Introduction

Patients receiving long-term ventilation (LTV) in out-of-hospital intensive care facilities often suffer from persistent impairments of their cognition, mental health and physical health, limiting their social participation. Chronically ill patients are often unable to express their care preferences. Thus, their medical care often lacks integration of patients’ wishes and values. Telemedicine may be used to collect patient-reported outcome measures (PROMs) from these patients to align medical care with their preferences. Early integration of teleconsultation to provide rapid support for specific patient symptoms can reduce economic costs.

Method and analysis

This is a multicentre, prospective, non-blinded, single-arm interventional trial with a pre-post design and follows the Standard Protocol Items: Recommendations for Interventional Trials statement. 10 out-of-hospital intensive care facilities in Berlin and Brandenburg, Germany, are grouped into three clusters. The study population includes adult patients (≥18 years) receiving LTV and residing in participating care facilities. During the preintervention phase, standard patient care remains unchanged. From the start of the intervention phase, enrolled patients receive telemedicine rounds in addition to standard care. These telemedicine rounds, conducted at least weekly, involve on-site healthcare professionals, patients and their relatives. Data are collected at predefined time points—study months 1,3, 9, 15 and 21—with a target of 57 participants at each time point. The study aims to evaluate whether a structured telemedicine intervention (1) increases the proportion of patients receiving record-documented PROMs in routine care and (2) reduces hospital readmissions. Secondary outcomes include the evaluation of post-intensive care syndrome, healthcare costs and the usability, applicability and perceived benefits of telemedicine. Additionally, qualitative interviews with patients, their relatives and healthcare professionals will explore individual experiences with chronic critical illness, the perceived quality of life of the patients and how team members manage moral distress in caregiving contexts. A mixed-effects logistic regression model will be used to analyse patients’ access to PROMs, while a mixed-effects Poisson regression model will be employed to evaluate hospital readmission rates. The findings may provide valuable insights into how telemedicine can improve patient-centred care for this particular patient group.

Ethics and dissemination

This study protocol received approval from the Ethics Committee of Charité—Universitätsmedizin Berlin, Germany (EA2/136/22). The findings will be disseminated through publication in a peer-reviewed scientific journal and presented at international conferences.

Trial registration number

This study was registered in the ‘German Register of Clinical Studies’ (DRKS; DRKS00029326).

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