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Evaluation of AT121 versus morphine on cortical neurons electrophysiology and dopamine concentrations in hippocampal cells

by Baraa E. Elawy, Chadi E. Soukkarieh, Abdul Q. Abbady, Shaza A. Allaham, Georges M. Deeb

In order to achieve pain relief without associated tolerance and dependence risks of general opioids like morphine, researchers have designed AT121 as potent safe alternative. In this study, we evaluated the analgesic and neurochemistry effects of AT121, a bifunctional partial agonist at Mu and nociceptin/orphanin FQ peptide (NOP) receptors, compared to morphine in hippocampal neurons for the measurement of dopamine neurotransmitters concentration and action potential of cortical neurons isolated from newborn BALB/c mice. This helps us to predict and assess its success in vivo by detecting the effect of AT121 in vitro. This activates G0/Gi protein pathways while blocking the β-arrestin pathway, significantly delayed action potential generation, prolonged spike duration, and reduced amplitude, without altering firing thresholds or inducing tolerance over a two-hour window. In contrast, morphine has produced similar analgesic effects but with a higher risk of tolerance. Co-administration of AT121 and morphine improved these changes, whereas naloxone failed to reverse AT121’s effects, suggesting distinct receptor interactions. Dopamine quantification in hippocampal culture media revealed that morphine, alone or combined with AT121, markedly elevated extracellular dopamine, consistent with its reinforcing properties to morphine on analgesia. Notably, AT121 alone led to significantly lower dopamine levels compared to control, indicating a reduced risk of triggering reward-related pathways. Together, these findings highlight AT121 as a promising candidate for both acute and chronic pain management, and suggest its offering potent analgesia with a lower likelihood of tolerance and addiction following chronic opioid exposure.

Economic evidence of health technology innovations for the diagnosis of extrapulmonary TB in resource-limited settings: a scoping review protocol

Por: Nyamasve · J. G. · Katena · N. A. · Shamu · S. · Mutsvangwa · J. · Esmail · A.
Introduction

Extrapulmonary tuberculosis (EPTB) poses a significant diagnostic and economic challenge in HIV endemic, low-resource settings due to its complex presentation and current diagnostic tools limitations. While accurate and timely diagnosis is critical for reducing morbidity, mortality and health system costs, economic evaluations of EPTB diagnostics remain sparse and fragmented. This protocol aims to map existing evidence on the economic evaluation of diagnostic innovations for EPTB in low-resource settings.

Methods and analysis

This scoping review protocol follows the Joanna Briggs Institute (JBI) methodological framework and registered on the Open Science Framework. Peer-reviewed articles, grey literature and official reports published between 2000 and 2025 will be searched in PubMed, MEDLINE, Google Scholar, Scopus and Science Direct. The search strategy is structured using the Population, Intervention, Comparator, Outcome, Time, Study design and Setting (PICOTSS) framework, and will be peer-reviewed using the Peer Review of Electronic Search Strategies (PRESS) guideline. Study selection, data charting and extraction will be performed independently by two reviewers. Data will be charted iteratively, and the methodological quality of selected economic evaluations will be appraised using the Drummond checklist. Results will be synthesised in narrative summaries and tabular formats. Final reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) reporting guideline.

Ethics and dissemination

For review of previously published data, ethical approval is not required. Findings will be disseminated in professional networks, stakeholder meetings and a peer-reviewed journal.

Trial registration number

OSF Registration DOI 10.17605/OSF.IO/BTCPG

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.

Vision Intervention for Seeing Impaired Babies: Learning through Enrichment (VISIBLE) - protocol of a feasibility pilot randomised controlled trial

Por: Guzzetta · A. · Bancale · A. · Bedoshvili · A. · Bosanquet · M. · Chorna · O. · Corsi · G. · Del Secco · S. · Elliott · C. · Fiori · S. · Fripp · J. · Gole · G. A. · Gordon · A. · Harpster · K. · Hunt · R. W. · Leishman · S. · Mori · R. · Morgan · C. · Novak · I. · Pagnozzi · A. M. · Pannek
Introduction

Visual impairment is reported to affect 40%–50% of children with cerebral palsy (CP). Vision difficulties in the context of rehabilitation are often under-recognised, under-treated and therefore under-studied, pointing to an urgent need for the development of evidence-based vision interventions for infants and toddlers with cerebral vision impairment (CVI). We present the protocol of a multisite pragmatic pilot randomised controlled trial (RCT) of feasibility, acceptability and preliminary efficacy of an early vision-awareness and parent-directed environmental enrichment programme for infants with or at risk of CP under 7 months corrected age (CA) with vision impairment.

The main objective is to determine the feasibility and acceptability of the Vision Intervention for Seeing Impaired Babies: Learning through Enrichment (VISIBLE) intervention. We will estimate the preliminary effects of the programme on infants’ visual functions and early development, as compared with standard community-based care (SCC).

Methods and analysis

A two-group RCT will be conducted. Infants at 3–6 months at entry, with severe visual impairment and at high risk of CP, will be enrolled and randomised (n=16 per group) to receive the VISIBLE intervention compared to SCC. Randomisation will be completed through an independent automated process (Research Electronic Data Capture). VISIBLE intervention will be delivered by a therapist through home visits (90–120 min) once every 2 weeks. Completion of 10 visits (80% of the intervention target dose) within 6 months is required for adherence to the VISIBLE trial. Outcome will be assessed at 12 months CA. Visual function will be evaluated with the Infant Battery for Vision, motor outcomes with the Peabody Developmental Motor Scales, Second Edition. Developmental quotients, infant quality of life, parent well-being and parent-infant relationship will be also monitored through standardised tools.

Ethics and dissemination

The enrolling sites have historically demonstrated rapid and effective translation of successful evidence-based interventions into routine clinical practice, as well as the dissemination of the findings through local, national and international scientific meetings.

Trial registration number

ACTRN12618000932268.

Retention in trials: a qualitative evidence synthesis of studies reporting participant reasons for trial non-completion

Por: Murphy · E. · Gillies · K. · Skea · Z. · Biesty · L. · Hunter · A. · Noor · N. M. · McCann · S.
Objectives

Poor participant retention in randomised clinical trials, resulting in missing outcome data, can impact the validity, reliability and generalisability of results. While participants’ views on general non-retention issues have been reported elsewhere, a qualitative evidence synthesis specifically focusing on trial processes (ie, outcome data collection) impacting retention has not been undertaken to date. This is an important research question to inform targeted interventions to support retention. This review aims to address this by systematically searching and synthesising the evidence on participant reasons for trial non-completion, linked to outcome data collection.

Design

We conducted a qualitative evidence synthesis of qualitative studies and mixed methods studies with a qualitative component, in Embase, Ovid MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Social Science Citation Index, Cumulative Index of Nursing & Allied Health Literature and Applied Social Sciences Index and Abstracts, up to February 2025. We used Thomas and Harden’s thematic synthesis approach. The Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative framework was used to assess confidence in the review findings.

Participants

We identified 11 studies reporting qualitative data from 14 separate trials, with findings from 105 trial non-retainers. The studies were undertaken between 2007 and 2025.

Results

There were three types of participant non-retention behaviours reported across the studies, where participants either: (1) missed at least one clinic visit; (2) did not complete a postal questionnaire or (3) did not complete online data collection. We developed four analytical themes outlining participant-reported influences on trial non-retention, specifically related to trial processes (ie, data collection for outcome measures): fluctuating health, balancing trial burdens, navigating life as a trial participant and managing expectations of participation.

Conclusions

This review generates important insights into participants’ reasons for trial non-completion linked to outcome data collection. The review highlights the need for further research into supporting trial recruitment discussions that provide clear, realistic expectations for potential trial participants, as well as strategies that recognise, and where possible, address some of the influences on participants to improve outcome data completeness and ultimately improve trial retention.

Mortality differences between ICUs that are regarded as 'in control: a longitudinal register-based study in the Netherlands, 2013-2023

Por: Termorshuizen · F. · Brinkman · S. · Arbous · S. M. · Dongelmans · D. A. · de Keizer · N. F. · Bakhshi-Raiez · F.
Objectives

Funnel plots are used to identify intensive care units (ICUs) with a higher than expected risk-adjusted mortality. ICUs with a standardised mortality ratio (SMR) within pre-defined control limits (often the 99.8% CL) are regarded as ‘in control’ and not labelled as a potential outlier for a particular calendar year. However, increased mortality rates not due to random fluctuations within and across the calendar years may be overlooked. We examined whether statistically significant and relevant differences in mortality over time between ICUs regarded as ‘in control’ are present.

Design

A longitudinal register-based study.

Setting and participants

88 ICUs in the Netherlands registering the admissions of all critically ill patients in the National Intensive Care Evaluation registry in the Netherlands from 2013 to 2023.

Primary outcome measure

Hospital death analysed in a multivariable logistic regression analysis with a random intercept for ICU. The random intercept variance was translated to the median OR (MOR).

Results

877 ICU-calendar year combinations were included, covering 759 498 unique admissions. The MOR increased from 1.12 (95% CI 1.10 to 1.15) for ICU-calendar year combinations with an SMR within the narrowest 95% CL (N=677) to 1.20 (1.17 to 1.24) for combinations with an SMR within the expanded 99.8% CL (including adjustment for overdispersion) (N=194) and to 1.21 (1.17 to 1.25) when including all ICU-calendar year combinations. Similar results were found for separate calendar years and separate diagnostic groups.

Conclusions

These results show differences in mortality between ICUs that were not labelled as outliers. Assessment of mortality performance should integrate cross-sectional funnel plots, the MOR and longitudinal trends in the SMR to better capture persistent patterns of excess risk.

Heart rate trends in healthy newborns >=35+0 weeks gestation after caesarean delivery with extrauterine placental transfusion and physiology-based cord clamping: a Norwegian observational study (INTACT-3)

Por: Saether · E. · Andersson · O. · Myklebust · T. A. · Bernitz · S. · Bjellmo · S. · Stridsklev · S. · Eriksen · B. H.
Objective

To describe the normal heart rate (HR) of healthy newborns ≥35+0 weeks’ gestation in the first 10 min after caesarean delivery (CD) with extrauterine placental transfusion, using dry-electrode ECG (NeoBeat).

Design

Single-centre, prospective observational study.

Setting

Norwegian County Hospital.

Patients

Newborns ≥35+0 weeks’ gestation delivered by CD under regional anaesthesia were eligible for inclusion. Newborns delivered by CD under general anaesthesia, or who needed medical intervention, were excluded.

Interventions

NeoBeat was attached to the newborn’s chest immediately following delivery. The placenta was delivered without cord clamping after 60–90 s and transferred with the newborn to a resuscitation table. Modified physiology-based cord clamping (PBCC) was performed.

Main outcome measures

HR was recorded every second for 10 min. HR quartiles were calculated. Events possibly influencing HR were annotated using Liveborn Observation App.

Results

89 newborns with a mean (SD) gestational age of 39+3 weeks (10 days) and birth weight of 3649 (536) g were included. Median (IQR) HR was 164 (117–176) and 169 (145–186) beats per minute at 20 s and 30 s, respectively, peaking at 169 (152–183) beats per minute at 4 min and then slowly decreasing to 157 (146–167) beats per minute at 10 min. HR was not significantly affected by intact-cord blood sampling (mean difference=5.4 (95% CI –1.4 to 12.1)), placental delivery (mean difference=0.7 (95% CI –3.5 to 4.9)) or cord clamping (mean difference =–0.6 (95% CI –2.1 to 0.9)).

Conclusions

This report describes, for the first time, HR quartiles for healthy newborns ≥350 weeks’ gestation from 15 s to 20 s and up to 10 min after CD with extrauterine placental transfusion and PBCC.

Antibiotic‐Loaded Calcium Sulphate Beads in Wound Management: A Scoping Review of Emerging Applications in Plastic and Reconstructive Surgery

ABSTRACT

Calcium sulphate (CS) is a fully synthetic, sterile, bioabsorbable biomaterial extensively applied for the management of infected tissues and postoperative dead spaces resulting from surgical interventions. Residual DS may facilitate hematoma accumulation and bacterial colonisation, thereby heightening the risk of surgical-site infections. Within orthopaedic surgery, CS has been predominantly evaluated as a bone-void filler and an off-label antibiotic delivery vehicle—particularly in arthroplasty revisions, chronic osteomyelitis, and open fractures—yielding high rates of infection prophylaxis, bone regeneration, and low complication profiles. Commercially available as injectable ‘pearls’ or beads, CS permits local, sustained antibiotic elution while undergoing gradual biodegradation, thus obviating the need for secondary removal procedures. Over the last decade, Calcium Sulphate beads (CSBs) have transcended orthopaedics, gaining traction across general, vascular, and endocrine surgery disciplines for the prevention and treatment of complex wound infections. However, their application in plastic and reconstructive surgery remains underreported, despite the specialty's frequent engagement with complex soft-tissue defects, bone exposure, suture dehiscence, and trauma-related wounds vulnerable to infection. To our knowledge, this represents the first scoping review synthesising current evidence, clinical indications, and emerging roles of CSBs within plastic and reconstructive surgery.

Comfort in a cross-sector care delivery model to address birth inequities: Learnings from San Francisco’s Pregnancy Village

by Osamuedeme J. Odiase, April J. Bell, Alison M. El Ayadi, KaSelah Crockett, Malini A. Nijagal, Patience A. Afulani

Introduction

Comfort is a key factor in physical and mental health, influencing overall well-being. Though once seen as peripheral to the patient care experience, it is now recognized as a critical outcome. For Black and other historically minoritized birthing individuals—who face racism, disproportionally higher morbidities, and unequal care—comfort is key to a safe, positive pregnancy experience. Innovative, community-driven models designed to improve comfort are therefore needed. San Francisco’s Pregnancy Village (PV) is a novel, cross-sector care delivery model providing a one-stop shop for clinical, city government, and wraparound services in a dignified and uplifting environment for Black and other minoritized pregnant individuals and their families. This study aims to examine comfort at PV and its key predictors.

Methods

We surveyed 114 participants (57 pregnant/postpartum individuals and 57 family members) between July 10, 2021 and June 30, 2022. Comfort was measured using a 3-item scale capturing the affective dimension of comfort, with scores standardized to 0–100 scale. Additionally, two individual items assessed situational aspects of comfort: (1) discomfort being seen at PV and (2) feeling out of place at PV. We performed univariate, bivariate, and multivariate analyses.

Results

The mean comfort score was 96.2/100 (SD = 11.4). Pregnant and postpartum participants, as well as those with limited social support, felt significantly less comfortable with the idea of being seen by friends at PV compared to family members and those with strong social support, respectively. Participants with some higher education and those reporting occasional everyday discrimination felt significantly less out of place at PV than those with a high school diploma or no discrimination experiences.

Conclusions

The Pregnancy Village model fostered generally high levels of comfort among Black and other minoritized pregnant individuals and their families in San Francisco, California. However, lower comfort levels among pregnant and postpartum individuals, those with lower educational attainment, and individuals lacking social support underscore the need for greater investment in co-led community-institutional, culturally responsive, and trauma-informed care approaches to foster comfort, particularly for those who face the severest inequities.

Patients experiences of the path to sarcoma diagnosis: a qualitative systematic review and thematic synthesis

Por: Schambye · M. E. R. · Kotter · M. F. · Rosing · J. A. M. · Dybdal · D. · Mathiasen · R. · Hjalgrim · L. L.
Objective

To explore existing qualitative research on patients’ experiences from the onset of symptoms to the diagnosis of sarcoma, with the purpose of identifying patient-perceived barriers at both patient and healthcare system levels and to highlight opportunities for improvement.

Design

Systematic review of qualitative studies using thematic synthesis.

Methods

We systematically searched Medline [Ovid], Embase [Ovid], PsycINFO [EBSCOhost] and CINAHL [EBSCOhost] from database inception to 11 April 2025 for qualitative studies reporting sarcoma patients’ experiences during their diagnostic trajectory. The final search was conducted on 11 April 2025. All articles were screened against predefined inclusion and exclusion criteria and methodological quality was appraised using the Critical Appraisal Skills Programme qualitative checklist. Six studies conducted in Australia, the Netherlands and the UK were included. Data were analysed using a thematic synthesis approach guided by Thomas and Harden (2008). Confidence in the synthesised findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation - Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERqual) approach.

Results

Four overarching themes emerged: patients’ experience and interpretation of symptoms, diagnostic pathways, healthcare system factors, and reflections and recommendations. Key contributors to delayed diagnosis were symptom normalisation, misattribution by both patients and healthcare professionals, limited continuity of care and communication challenges. These findings were consistent across multiple countries, indicating relevance and validity in many settings. Patients emphasised the importance of disease awareness, persistence of patients and coordinated care.

Conclusions

Diagnostic delays in sarcoma are influenced by both patient and healthcare systemic factors. Addressing these factors requires increased disease awareness among healthcare professionals and the public, improved coordination within the healthcare system, and targeted research to guide future interventions. This review provides cross-country insights into barriers to early sarcoma diagnosis, informing future priorities in clinical practice and research.

PROSPERO registration number

CRD420251030726.

N-terminal proBNP adds prognostic value to high-sensitivity cardiac troponin I in elective thoracic surgery: an observational cohort study

Por: Alonso · M. · Popova · E. · De Miguel · M. · Garcia-Osuna · A. · Gonzalez-Tallada · A. · Ordonez-Llanos · J. · Jauregui · A. · Trujillo · J. C. · Martin Grande · A. · Martinez-Tellez · E. · Parera · A. · Planas · G. · Trujillo · L. · Butron · D. · Sola-Roca · J. · De Nadal · M.
Background

Perioperative myocardial injury (PMI) is a common complication following non-cardiac, particularly thoracic, surgery and is associated with increased cardiovascular risk. Although guidelines recommend cardiac biomarker monitoring to detect PMI, its implementation in routine clinical practice remains limited.

Objective

To evaluate the combined use of high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting major adverse cardiovascular events (MACE) following elective thoracic surgery, and to determine whether NT-proBNP provides incremental prognostic value beyond hs-cTnI alone.

Design

Multicentre observational cohort study.

Setting

Conducted between February 2021 and November 2023 in three Spanish tertiary hospitals.

Participants

Patients aged ≥45 years scheduled for elective thoracic surgery involving lung resection (pneumonectomy, lobectomy, bilobectomy or segmentectomy) under general anaesthesia. Exclusion criteria included urgent or non-thoracic surgery, active infection or sepsis and a history of severe heart failure (ejection fraction

Main outcome measures

Combined measurement of hs-cTnI and NT-proBNP at baseline (preoperatively) and at 24 and 48 hours postoperatively.

PMI was defined as hs-cTnI ≥45 ng/L at 24 and/or 48 hours or a ≥20% increase from baseline in patients with elevated preoperative concentrations.

Results

Among 475 patients, PMI occurred in 11.8%. PMI had higher rates of prior stroke (12.5% vs 2.9%; p=0.004), smoking history (85.7% vs 64.0%; p=0.001) and severe renal dysfunction (7.1% vs 0.7%; p=0.001), with similar Revised Cardiac Risk Index distribution. Patients with PMI also had greater postoperative elevations of hs-cTnI and NT-proBNP (p

Conclusions

Combined hs-cTnI and NT-proBNP assessment improves perioperative cardiovascular risk stratification beyond ischaemia.

Trial registration number

NCT04749212

Biopsychosocial trajectories in older adults with planned intensive care: a protocol for a prospective observational study (GeriICU)

Por: Schumann · J. · Köhring · W. · Simm · A. · Grosskopf · A. · Szabo · G. · Schneider · T. · Prell · T.
Background

Older adults admitted to intensive care units (ICUs) following elective surgery face heterogeneous trajectories of recovery spanning the physical, cognitive and social domains. Biological ageing processes, including cellular senescence, may modulate these outcomes. Here, we present the protocol for an analytic prospective observational cohort study integrating biopsychosocial assessments and senescence-associated biomarkers to identify predictors of health-related quality of life (HRQoL) and post-ICU recovery.

Methods and analysis

Single-centre, prospective cohort study at the University Hospital Halle (Saale), Germany. Adults aged 60 years or older scheduled to undergo elective surgery and who have a planned postoperative stay in the ICU of at least 24 hours and who are able to provide consent will be enrolled. Baseline pre-ICU data will include the following: medical history, comorbidity, medications, routine laboratory values and a comprehensive geriatric assessment (eg, frailty, mobility, handgrip strength, Timed Up & Go, cognition, mood, loneliness, social status and EuroQol 5-Dimension 5-Level, EQ-5D-5L). A 5 mL serum sample will be collected for a senescence-associated secretory phenotype panel and additional ageing biomarkers. Skin autofluorescence will be used to estimate advanced glycation end-products. Telephone follow-ups at 3 and 6 months ascertain HRQoL, functional outcomes, psychosocial outcomes, rehospitalisations and institutionalisation. The primary endpoint is defined as a stable or improved HRQoL (EQ-5D-5L) at 3/6 months vs baseline. We intend to use multivariable predictive modelling with elastic-net regularisation and conduct internal validation using bootstrap resampling and cross-validation.

Ethics and dissemination

This study has been approved by the Ethics Committee of the Medical Faculty, Martin-Luther-University Halle-Wittenberg (No. 2025-112). Written informed consent is obtained from all participants. The results of this study will be reported in a peer-reviewed journal.

Trial registration number

DRKS00037969.

Early mobilisation after abdominal surgery: a concept analysis

Por: Schandl · A. · Siesage · K. · Kroksmark · A.-K. · Gruber-De Sousa · E. · Lilliecrona · J. · Olsen · M. F.
Objective

To clarify and define the clinical practice concept of early mobilisation after abdominal surgery.

Design

A concept analysis guided by Walker and Avant’s method.

Data sources

MEDLINE (Ovid), AMED-(Ovid), Embase (Elsevier) and CINAHL (EBSCO) were searched through 5 December 2024.

Eligibility criteria

Relevant studies that included combinations of the terms ‘early mobilisation’, ‘early ambulation’, ‘early acceleration’, ‘abdominal surgery’ and ‘surgical procedures’ were selected. We restricted the search to English full-text publications involving adult patients, limited to the year 2000 and onward. Inclusion criteria were original research articles describing the timing and/or type of mobilisation.

Data extraction and synthesis

The study derives its defining attributes, antecedents and consequences through data analysis. To enhance understanding of the model, we constructed related and contrary cases of the concept and outlined relevant empirical referents.

Results

In total, 140 studies were included in the analysis. Early mobilisation is characterised by the key defining attributes of initiating active physical movement, including standing, sitting in a chair or walking, within the first 24 hours of surgery. Antecedents include haemodynamic and respiratory stability, adequate pain management, and the patient’s cognitive and physical readiness. Contextual antecedents include competent and adequately staffed healthcare teams. Consequences include improved physiological recovery and enhanced postoperative outcomes.

Conclusions

This analysis provides a clarified, practice-focused definition of early mobilisation after abdominal surgery. By delineating its key attributes and contextual prerequisites, the study offers a conceptual foundation that can support clinical guidelines, promote consistent implementation and inform future research aimed at optimising postoperative recovery.

Cost-effectiveness of osteoporotic fracture risk assessment in people with intellectual disabilities: a UK NHS modelling study

Por: Png · M. E. · Frighi · V. · Holt · T. A. · Achana · F. · Smith · M. C. · Collins · G. S. · Roast · J. · Petrou · S.
Objectives

We compared the cost-effectiveness of alternative fracture risk assessment strategies for people with intellectual disabilities (ID) aged ≥40 years from a UK National Health Services perspective over a lifetime horizon.

Design

Cost-effectiveness analysis using a lifetime decision-analytical model.

Setting

UK primary care, with data from literature and national databases.

Participants

People with ID.

Interventions

Three strategies were assessed: (S1) Risk assessment using the UK QFracture score; (S2) use of IDFracture (a fracture risk prediction tool specifically developed for adults with ID); and (S3) conducting a one-time dual-energy X-ray absorptiometry (DXA) scan in all. S1 and S2 were followed by DXA scan for those at risk. At-risk individuals received treatment according to UK practice (bisphosphonates plus vitamin D and calcium for osteoporosis, and vitamin D and calcium alone for osteopenia).

Primary outcome measures

Direct healthcare costs and quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER).

Results

In the base case, S2 (ICER: –£2568/QALY) was dominant (ie, less costly and more effective) and S3 (ICER: £1678/QALY) was cost-effective relative to S1 for major osteoporotic fracture (MOF). For hip fracture, S2 (ICER: £32 116/QALY) and S3 (ICER: £49 536/QALY) were not cost-effective relative to S1 under the National Institute for Health and Care Excellence-recommended cost-effectiveness thresholds. Findings from the sensitivity analyses were predominantly consistent with the base-case results. Subgroup analyses showed that age-specific and gender-specific strategies could be used.

Conclusion

For people with ID aged ≥40 years, a proactive approach to risk assessment for MOF is not only clinically beneficial, but also cost-effective.

Primary carE PPi dEprescRibing (PEPPER) trial: a protocol for determining the optimal strategy for stopping chronic proton pump inhibitor therapy in primary care patients

Por: Carbone · F. · Scheepers · J. · Van den Houte · K. · Laenen · A. · Tack · J.
Introduction

Current Belgian guidelines state that chronic proton pump inhibitor (PPI) therapy is indicated for oesophagitis grade C and D, Barrett’s oesophagus, Zollinger-Ellison syndrome, or to prevent bleeding ulcers with chronic non-steroidal anti-inflammatory drugs (NSAID) intake in patients at risk. Guidelines justify empiric short-term PPI therapy in other cases to control symptoms. Yet, there is insufficient PPI down-titration and/or cessation. As such, concerns have risen related to the impact of PPIs on the healthcare budget and increasing number of risks and side effects. This study aims to provide evidence to determine which strategy provides the most effective approach for stopping chronic intake of PPIs in patients in whom there is no firm medical indication for their continued use.

Methods and analysis

This is a multicentre, pragmatic, randomised clinical trial. General practitioners will randomise 609 to one of three PPI deprescription strategies. Patients on a high-dose PPI are allowed to participate after down-titrating their dose to a maintenance dose for 1 month before being randomised. Patients unable to decrease the high-dose PPI are not to be randomised. Following randomisation, patients will be requested to adapt their PPI intake for 1 month to the allocated deprescription scheme: (a) on-demand PPI intake, (b) replace PPI to alginate intake and (c) intermittent PPI intake with a fixed scheme. After successfully following the deprescription strategy, patients are requested to completely stop their use of PPI. Patients are followed up for 1 year. The primary endpoint of the study is the percentage of patients achieving a successful therapeutic outcome, defined as limited PPI intake and willingness to continue the therapy, at the end of the follow-up period. Data will be collected using a study-specific online platform and analysed using the intention-to-treat approach.

Ethics and dissemination

This trial was approved through the platform for Clinical Trials in the European Union by a Belgian ethics committee (CTIS reference: 2022-502375-37-00). Study results will be disseminated via open-access, peer-reviewed publications and conference presentations. Trial registration number NCT05629143.

Trial registration number

NCT05629143, clinicaltrial.gov.

Implementation of a digital tool for monitoring and managing the emotional and cognitive sequelae of post-intensive care syndrome: ICURA study protocol for a randomised clinical trial

Por: Llabres-Alvarez · E. · Riera-Sagrera · M. · Llompart-Casasnovas · A. · Salva · P. · Castro · A. · Godoy-Gonzalez · M. · Dona-Lopez · E. · Lopez-Aguilar · J. · Jodar · M. · Navarra-Ventura · G. · Gili · M. · Roca · M. · Fernandez-Gonzalo · S.
Introduction

Intensive care units (ICUs) can be a particularly challenging environment for patients who are mentally vulnerable. In addition to the physical stress associated with critical illness and its management, there are physiological and psychosocial factors that can negatively impact a patient’s mental health. Approximately half of ICU survivors will experience post-intensive care syndrome, a set of emotional, neuropsychological and physical sequelae that can significantly affect patients’ functionality and quality of life, both in the short and long term. The main objective of this study is to investigate whether the ICU Recovery Answers (ICURA) digital follow-up platform can effectively detect emotional and cognitive problems in critically ill patients and its impact on functionality and health-related quality of life during the first year after ICU discharge.

Methods and analysis

Multicentre longitudinal prospective study involving ICU adult patients, with randomised follow-up comparing a telemedicine monitoring programme versus usual medical care during 1 year after discharge. A total of 360 participants will be recruited during their ICU admission in two hospitals in Spain. Efficacy outcomes will focus on participants’ level of functioning, assessed with the WHO Short Disability Assessment Schedule, and quality of life, measured with the 12-Item Short Form Survey at 1, 6 and 12 months after ICU discharge. Emotional state and cognitive impairment will be evaluated using the Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 and Treatment-Outcome Post-Traumatic Stress Disorder Scale and the Montreal Cognitive Assessment by telephone at 1, 3, 6, 9 and 12 months after ICU discharge.

Ethics and dissemination

The implementation of this project is expected to have a direct impact on the satisfaction of ICU survivors, improving their well-being, personalised follow-up and quality of life. Results from this study will be disseminated at various scientific conferences, national and international meetings, and will be shared with the general public and other relevant parties. The dissemination of these results will occur through scientific publications, allowing the medical and scientific community to benefit from the study’s findings. Ethics approval from the Ethics Board of Parc Taulí Foundation and Balearic Islands with reference numbers 2022/3031 and IB 5072/22 PI: Protocol version 1 of 18 November 2022.

Trial registration number

NCT06504979.

'Its not just diabetes: implementation enablers and barriers of an indigenous-focused virtual diabetes care clinic using the Consolidated Framework for Implementation Research (CFIR) - a qualitative assessment

Por: Swampy · K. · Eurich · D. T. · Meneen · K. · Samanani · S. · Singh · P. · Wozniak · L. A. · Padwal · R. S. · Lau · D.
Introduction

Indigenous peoples living with diabetes face unique challenges accessing comprehensive specialty diabetes care. A small diabetes virtual care clinic oriented towards Indigenous individuals, and those in rural and remote communities, has provided care to over 400 individuals.

Objectives

We characterised the distinguishing features of care provided at this clinic and used the Consolidated Framework for Implementation Research 2.0 (CFIR) to explore the enablers and barriers to implementing this model of care, from the perspective of the clinic’s staff and providers.

Research methods and design

Guided by CFIR, we conducted eight semi-structured interviews with six clinic staff members. Deductive thematic analysis was used to identify relevant enablers and barriers.

Results

The aspirational features of care were cultural safety, comprehensiveness and virtual delivery. The implementation of this model of care was enabled by an internal culture of relational care; a nimble, resourceful, pragmatic and client-centred approach to virtual delivery; wayfinding and resources from key external organisations; community engagement and a small team of motivated and independent providers. Key barriers included the lack of physical interactions and uncertain or limited resources and funding.

Conclusion

The identified enablers and barriers to implementing an Indigenous-focused virtual diabetes care clinic have implications for future interventions to improve rural Indigenous chronic disease care, and for governments and adjacent organisations tasked with meeting Canada’s Truth and Reconciliation Commission’s calls to action in healthcare. Further research examining the effectiveness of virtual diabetes care at this clinic is ongoing.

Report cards and outcome measurements to improve the safety of surgical care (North America): an updated systematic review from Making Healthcare Safer IV

Por: Huy · T. · Blegen · M. B. · Tupper · H. · Premji · A. · Motala · A. · Lawson · E. · Shekelle · P. G. · Girgis · M. · Maggard-Gibbons · M.
Objectives

In the USA, an estimated 40–50 million operations are performed annually, with high rates of adverse events. Since the 1980s, report cards have been used for outcome measures and to improve safety of surgical care. As part of Making Healthcare Safer IV—an initiative aimed at publishing evidence-based reviews as they are completed to help healthcare leaders, researchers and policymakers act more quickly on evidence-supported practices—we performed an updated review on the certainty of evidence on patient safety practices related to the use of surgical report cards and outcome measurements.

Design

Systematic review using the Grade of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Data sources

PubMed, Web of Science, Scopus and the Cochrane Library were searched from November 2011 to May 2023.

Eligibility criteria for selecting studies

We included primary research studies (randomised control trials or observational studies with a comparison group, including pre–post studies) or observational studies that investigated a surgical report card in adult or paediatric surgical patients at the hospital or surgeon level in inpatient or outpatient settings. Excluded studies included: narrative reviews, scoping reviews, editorials, commentaries, abstracts, studies that measured only patient knowledge or levels of engagement or studies using local surgical dashboard data.

Data extraction and synthesis

Screening and eligibility were done in duplicate, while data extraction was done by one reviewer and checked by a second reviewer. Specific items in the Risk Of Bias In Non-randomised Studies - of Interventions tool and a modification of the National Institutes of Health Tool were used to assess for bias in studies. Two reviewers assessed each study for risk of bias. A modified version of the GRADE framework was used to assess the certainty of evidence.

Results

We identified 19 studies that met the inclusion criteria: 13 primary research studies and 6 descriptive studies of surgical collaboratives. Of the primary studies, nine used a pre–post or longitudinal study design and four used a regression discontinuity or concurrent controlled design. Seven of the studies were about the American College of Surgeons National Surgical Quality Improvement Project. Five studies were from single institutions and the remainder included nine to greater than 700 hospitals. Pre–post studies of report cards that prompted quality improvement (QI) programmes all reported improvements in outcomes, longitudinal studies reported benefits in some but not all outcomes and one in four controlled before-and-after studies reported a statistically significant mortality benefit. All studies, except for one, were at moderate or high risk of bias. Six collaboratives were identified with preliminary data.

Conclusions

Based on the above evidence, the theoretical rationale and parallel evidence in other settings, we judged that it was moderate certainty that report cards and outcomes measurements can improve surgical outcomes. However, given the evidence from studies where report cards were actively linked to institutional QI initiatives, we recommend that outcome data must be paired with actionable QI efforts to meaningfully improve patient outcomes.

Dapagliflozin for cardiorenal protection after intensive care unit discharge: a protocol for a randomised controlled trial evaluating dapagliflozin at ICU discharge for cardiorenal protection (DAPA-ICU)

Por: Depret · F. · Chousterman · B. · Roger · C. · Garnier · M. · Lalande · R. · Kerforne · T. · Rouve · E. · Lukaszewicz · A.-C. · Ouattara · A. · Merdji · H. · Turbil · E. · Bouhemad · B. · Quenot · J.-P. · Delbove · A. · Levrat · Q. · Jully · M. · Legriel · S. · Bougouin · W. · Klouche · K.
Introduction

Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors.

Method and analysis

This is a multicentre, double-blind, randomised, placebo-controlled clinical trial conducted across 16 teaching and non-teaching ICUs in France. We will enrol 600 adult patients (18 years of age or older) who have received mechanical ventilation and/or vasopressors for at least 24 hours during their ICU stay, and who meet at least one of the following criteria at ICU discharge: N-terminal pro-B-type natriuretic peptide (NT-proBNP) >800 pg/mL or BNP >90 ng/L, an estimated glomerular filtration rate between 25 and 90 mL/min/m². Eligible patients will be randomised in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or a matching placebo for a duration of 1 year. The primary outcome is a composite endpoint assessed at 1 year after randomisation, comprising: all-cause mortality, unscheduled hospitalisation for acute heart failure and decrease in renal function. Feasibility will be assessed based on patient and clinical acceptability and recruitment performance, including enrolment rates across participating centres.

Ethics and dissemination

This study has been approved by the Institutional Review Board (CPP Ile-de-France 5). Written informed consent will be obtained from all participants prior to enrolment and the initiation of any study-related procedures. Dapagliflozin is a widely available medication with an established safety profile. If proven effective, it would represent a readily deployable strategy to improve long-term outcomes in ICU survivors. The study is described in accordance with the Standard Protocol Items: Recommendations for Interventional Trials framework, and key design features and methodological decisions are outlined accordingly. DAPA-ICU aims to evaluate the efficacy of dapagliflozin in cardiorenal protection among critically ill patients following ICU discharge. The main trial results will be submitted for publication in a peer-reviewed journal as soon as they become available after final analysis.

Trial registration number

NCT07025629.

Development of the PREDICT-Kidney online tool to promote informed decision-making about kidney cancer follow-up care: a qualitative co-design study

Por: Re · C. · Stimpson · G. · Stewart · G. D. · Bromley · J. · Archer · S. · Batley · C. · Godoy · A. · Usher-Smith · J. · Harrison · H.
Objective

Co-design of the PREDICT-Kidney online tool by patients, members of the public and healthcare professionals (HCPs), to support the communication of the risk of recurrence following surgical treatment for kidney cancer.

Design

Qualitative co-design study. Using an iterative process, feedback was collected (via workshops), prioritised and implemented.

Setting

Online workshops with participants from across the UK were conducted between December 2023 and November 2024.

Participants

18 adult participants, including patients surgically treated for kidney cancer, members of the public without a history of kidney cancer and HCPs involved in kidney cancer care.

Primary and secondary outcomes

To produce an online tool to support the communication of risk of kidney cancer recurrence that is easy to use, easy to understand and acceptable to stakeholders. Secondary outcomes are the properties of the feedback collected, including volume and type.

Results

Across nine workshops, 99 discrete feedback items were collected, resulting in 71 actionable changes to the initial prototype tool. Differences in priorities were observed between participant groups, especially around the inclusion of information about competing risks of death. Participants valued the tool for improving consistency of follow-up information, supporting shared decision-making and providing multiple visual formats to communicate risk. Iterative feedback led to refinements in terminology, design, content and delivery, including adjustments to the presentation of recurrence and mortality risk.

Conclusions

A co-design approach was used to improve the PREDICT-Kidney online tool to align with the needs of patients and HCPs. A feasibility study is required to evaluate its use and impact in clinical practice.

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