Virtual Wards (VWs) facilitate hospital-level monitoring, diagnostics and treatment within patients’ homes, while the hospital team retains responsibility for care. International research indicates that VWs decrease hospital length of stay without increasing readmissions; however, the feasibility and key operational determinants within Dutch care remain uncertain. This protocol outlines the VW for Early Discharge in Patients Receiving Inpatient Care (VIP Care) study.

The VIP Care study is a single-centre prospective feasibility cohort study conducted at Erasmus University Medical Center (Erasmus MC), Rotterdam, the Netherlands. The study encompasses seven predefined subcohorts with n=51 eligible patients per subcohort: (1) bacterial, fungal or parasitic infections; (2) viral respiratory infections; (3) dehydration; (4) decompensated heart failure; (5) high-dose corticosteroid treatment; (6) post-transsphenoidal pituitary surgery follow-up and (7) severe inflammatory skin disease with or without bacterial or viral superinfection. Adults who require hospital-level monitoring and/or therapy may qualify for early discharge to the VW.

The VW integrates scheduled, patient-performed measurements using (European Conformity) CE-marked devices with structured symptom assessment submitted via a patient application, and data review in an electronic health record-integrated clinician cockpit. Submissions are evaluated by VW tele-nurses using prespecified Early Warning Score based thresholds and an escalation protocol. Patients receive a daily physician telephone review. Diagnostics and treatments are administered at home to hospital standards through established home-care services.

The primary outcome (feasibility) is adherence to transfer, defined as the proportion of eligible inpatients who provide written informed consent and are subsequently successfully transferred to the VW. The prespecified feasibility threshold is 30%. Secondary outcomes include reach (eligibility, invitation and consent rates among admitted patients), operational performance during the VW episode (alert frequency and handling, contact volumes and actions), length of stay on the ward and in the VW, emergency department reassessments and 30-day readmissions. Qualitative interviews will be conducted to identify implementation determinants.

The study received approval from the Erasmus MC Medical Ethics Committee (MEC-2024–0060; amendment MEC-2024–0060 A0001). Incremental risk is considered minimal. Written informed consent is obtained. Findings will be disseminated through peer-reviewed publications, conference presentations and an accessible lay summary.

ClinicalTrials.gov NCT06936891; CCMO NL85516.078.24. Recruitment began in May 2025 and is ongoing.

Young children and children living with HIV are at high risk of progressing to tuberculosis (TB) disease following Mycobacterium tuberculosis (Mtb) exposure and infection, and also of developing severe forms of disease and TB-related mortality. Identifying children who have very early (sub-clinical) TB disease, prior to progression to clinically apparent TB, would mean that TB preventive treatment (TPT) could be more efficiently targeted to this group. Identifying biomarker changes on drug therapy in children with Mtb infection or very early disease could pave the way for the development of tests that can identify which children have viable bacilli and are therefore at increased risk of disease progression.

The INTREPID study will use already collected samples taken from well-phenotyped paediatric cohorts in three clinical studies conducted in South Africa in children Mtb exposure to disease and from children treated for Mtb infection and early TB disease, as well as targeted Mtb antibody analysis. Data on viral co-infections and relevant clinical and epidemiological parameters will be integrated and evaluated to identify the optimal biosignatures that can predict future progression to clinically overt disease in children below 5 years of age, including those living with HIV.

The study protocol received ethical approval from the Stellenbosch University Health Research Ethics Committee (N23/03/025). The study findings will be disseminated through peer-reviewed publications, scientific conferences and formal presentations to healthcare professionals and to local communities, in collaboration with the Desmond Tutu TB Centre Community Advisory Board.

Concentration of care and collaborations between hospitals increasingly reorganise oncological care into Comprehensive Cancer Networks (CCNs), aiming to improve care outcomes and reduce costs. This study aims to evaluate the effect of four CCNs on healthcare cost and outcomes for patients with colon or pancreatic cancer.

We performed a retrospective cohort study based on claims data in the Netherlands. Data included patient characteristics, health insurance claims and healthcare activities. All costs were indexed to Euro 2023. We performed propensity score matching per CCN and applied regression models with a difference-in-difference design, adjusting for non-linear trends before the start of a CCN.

The study was conducted within the Dutch healthcare system, analysing claims data representative of hospital-based cancer care.

A total of 92 309 patients with colon cancer and 25 630 patients with pancreatic cancer were included. Patients were identified through health insurance claims between January 2013 and June 2021.

Implementation of four CCNs, which included structured collaboration between healthcare organisations. Follow-up duration was 2 years post-diagnosis.

Primary outcomes included 2-year oncological healthcare costs and 2-year mortality rate. Secondary outcomes involved care process indicators: referral rates and double diagnostics (an identical diagnostic activity performed within 4 weeks after referral to a secondary hospital).

For colon cancer, one CCN showed a significant decrease in 2-year oncological costs (–1899). One CCN showed a significant decrease in referrals (–3.6%) and one a significant increase (+4.4%). No significant effect on 2-year mortality and double diagnostic activities was found. For pancreatic cancer, one CCN showed a significant decrease in 2-year oncological costs (–3747) and one CCN showed a significant increase in double diagnostic activities (+8.6%). No significant effect on referrals and 2-year mortality was found.

CCNs do not consistently reduce costs or affect referral patterns or redundant diagnostics. No impact on mortality was found. Additional insights into determinants of CCN success are required before broad implementation is warranted.

To test the agreement and usability of a novel quality appraisal tool: A MeaSurement Tool to Assess systematic Reviews of Prognostic Factor studies (AMSTAR-PF).

Observational study.

14 appraisers of varied experience levels and backgrounds, including undergraduate, master’s and PhD students, postgraduate researchers, research fellows and clinicians.

Eight systematic reviews were rated by all reviewers using AMSTAR-PF.

Planned measures included intrapair and inter-pair agreement using Cohen’s and Fleiss’ kappa, time of use and time to reach consensus. Interrater agreement was an added measure, and Gwet’s agreement coefficient was calculated and presented due to its greater stability across agreement levels. The percentage of intrapair agreements identical or one category apart was also presented.

Interrater agreement averaged 0.59 (range 0.21–0.90), inter-pair agreement 0.61 (range 0.24–0.91) and intrapair agreement 0.75 (range 0.45–0.95) across the domains, with agreement for the overall rating 0.46 (95% CI 0.30 to 0.62) for interrater agreement, 0.46 (95% CI 0.17 to 0.74) for inter-pair agreement and 0.68 (range of averages 0.22–1.00) for intrapair agreement. The majority (60.7%) of intrapair ratings were identical, with 94.6% of final ratings either identical or only one category different for the overall appraisal. The time taken to appraise a study with AMSTAR-PF improved with use and averaged around 34 min after the first two appraisals.

Despite some variance in agreement for different domains and between different appraisers, the testing results suggest that AMSTAR-PF has clear utility for appraising the quality of systematic reviews of prognostic factor studies.

Chronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD), are among the leading non-communicable diseases (NCDs) worldwide. However, diagnosing CRDs in low-income and middle-income countries (LMICs) remains challenging due to limited access to spirometry and trained professionals. Aggravating the burden, CRDs often coexist with other NCDs, increasing healthcare costs, reducing quality of life and elevating mortality. These challenges highlight the need for simple case-finding approaches for CRDs, such as the COPD in Low-Income and Middle-Income Countries Assessment (COLA-6) questionnaire, to support prompt identification and appropriate care within NCD services in LMICs.

To evaluate the discriminative accuracy, feasibility and implementation of the COLA-6 questionnaire in identifying and managing CRDs in Brazilian Primary Healthcare (PHC) services for NCDs.

The Multimorbidity Approach for REspiratory Solutions (MARES) study consists of three work packages to be conducted in PHC services in São Carlos/SP and São Paulo/SP, Brazil.

MARES-1: A cross-sectional observational study enrolling 859 individuals with at least one NCD receiving care in PHC. The COLA-6 questionnaire will be administered by the research team and compared with quality-assured spirometry. The Chronic Airways Assessment Test (CAAT), Asthma Control Questionnaire (ACQ-7) and fractional exhaled nitric oxide (FeNO) will also be assessed. The diagnostic performance of COLA-6 for identifying CRDs—including COPD, asthma, preserved ratio impaired spirometry, restriction and overlaps—will be assessed using area under receiver operating characteristic curves and 95% CIs.

MARES-2: A cross-sectional observational study enrolling 20 healthcare professionals (physicians, physiotherapists, community health agents and nurses) from five PHC services. These professionals will apply the COLA-6 during routine NCD care to a total sample of 1000 patients. Qualitative interviews will be conducted to explore barriers and facilitators to the implementation of COLA-6, using deductive thematic analysis.

MARES-3: A longitudinal, prospective observational study in which patients from MARES-1 and MARES-2 will be reassessed at 6-month follow-up. A total sample of 473 participants with abnormal spirometry, a diagnosis of CRD or high risk for CRDs is expected. Participants will undergo spirometry, and a subset will be interviewed to explore their healthcare experiences through qualitative thematic analysis. Access to diagnostic and treatment services in Brazil will be assessed. Changes in spirometry values, FeNO, CAAT and ACQ-7 scores from baseline to 6 months in patients from MARES-1 will be analysed.

This study has been approved by the Ethics Committees of Federal University of São Carlos and University of Santo Amaro (UNISA). Ethical approval was also granted by the University College London. Results will be disseminated through peer-reviewed medical journals and presentations at international conferences. Results will improve identification of CRDs, addressing a significant gap in current PHC settings.

NCT07050823/NCT07093021/NCT07134855.

Post-COVID syndrome manifests with a diverse array of symptoms for which no standard care plan currently exists. Many questions were raised by patients, which underscored the need for a validated patient-reported outcome measure (PROM). Therefore, a post-COVID module was developed to be included in the Assessment of Burden of Chronic Conditions (ABCC-) tool. The ABCC-tool evaluates and visualises the perceived physical, emotional and social burden of one or multiple chronic disease(s) using a balloon diagram and aims to facilitate person-centred care and structured discussions between patients and healthcare professionals. This study explores the patients’ perspective on the content of the ABCC-tool for post-COVID and the tool’s usability in a home-based setting.

All patients who completed the ABCC-tool for post-COVID were invited for an online semi-structured interview. We selected post-COVID patients who had used the tool in the past three months. Interviews were audio recorded and analysed using a thematic approach with Atlas.ti version 23.

Nineteen post-COVID patients (10 males, mean age 56) were interviewed between May and August 2024. The tool was regarded as user-friendly, and patients indicated they would use the tool again in the future. Patients valued the tool’s broad range of topics, some of which are often overlooked in standard healthcare consultations. The tool was comprehensible and relevant according to all patients. The balloon diagram was easy to understand, but a legend explaining the colours of the balloons was preferred. Other suggestions for improvement included adding open-text fields and periodic reminders to increase usability and adding long-term data.

The ABCC-tool is a promising instrument for post-COVID patients, offering a structured way to monitor and communicate experienced burden in addition to standard healthcare consultations. Refinements addressing usability and comprehensiveness are recommended to facilitate its integration into clinical practices.

Current pharmacological treatment options for painful diabetic neuropathy (PDN) often fail to provide adequate pain relief. However, in the recent SENZA-PDN study, high-frequency 10 kHz spinal cord stimulation (SCS) demonstrated significant long-term improvements in lower limb pain and health-related quality of life (HRQoL) in a PDN population. Furthermore, more than half of 10 kHz SCS recipients showed improved sensory function based on non-blinded clinical assessments in post hoc analysis. We report the design of the PDN-Sensory study, which aims to evaluate changes in pain and neurological function with 10 kHz SCS in the treatment of PDN. The study will include objective measures of neurological function, including the modified Toronto Clinical Neuropathy Score (mTCNS) and intraepidermal nerve fibre density (IENFD).

This multicentre, prospective, randomised controlled trial will compare conventional medical management (CMM) with 10 kHz SCS+CMM in individuals with diabetes and chronic, intractable lower limb pain due to PDN. Participants will be randomised 1:1 to CMM alone or 10 kHz SCS+CMM, with optional crossover at 6 months. The primary outcome is the proportion of participants at 6 months achieving ≥50% pain relief from baseline. The key secondary endpoint is the proportion of participants at 6 months with a reduction in mTCNS of ≥3 points from baseline (excluding changes in foot pain). Additional endpoints at 6 and 12 months include changes from baseline in mTCNS, IENFD, 7-day averaged pain score, pain-related interference, HRQoL, sleep, psychological outcomes, functional status and metabolic parameters.

The study protocol received central approval from the Western Institutional Review Board (IRB #20230954). Local IRB approval will be required before initiation of the study at each participating clinical site. The study complies with Good Clinical Practice guidelines (ISO 14155), the Declaration of Helsinki, and all applicable national, federal and local regulatory requirements. Dissemination plans include presentations at national and international conferences and publication in a peer-reviewed journal with open access.

NCT05777317.

Neutropenic fever (NF) has a crude mortality rate of 3–18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone.

This pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients’ blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay.

The institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing.

NCT06794320.

To examine health and social service use pre- and post-cochlear implant in adults.

A retrospective cohort study.

All public and private hospitals in Australia.

A total of 3033 adults aged ≥18 years who received a cochlear implant in Australia between 1 January 2014 and 31 December 2018 were included. Participants were followed for 3 years pre-implant date and 3 years post-implant date or until death. Data were sourced from the Person Level Integrated Data Asset.

The study examined the (i) number of visits to general practitioners (GPs), specialists and audiologists; (ii) fee charged, benefit paid and out-of-pocket (OOP) expenses for health services; (iii) personal income; (iv) completion of higher education and post-high school vocational education and training and (v) number of government benefits and concession cards received.

The mean age of adults at cochlear implantation was 63.3 years (SD 16.1). Over the 3 years period before and after implantation, the mean number of GP visits remained stable (24.5 pre-implant vs 24.7 post-implant), specialist visits decreased (6.4 pre-implant vs 5.3 post-implant) and audiologist visits increased (1.7 pre-implant vs 6.6 post-implant). Higher GP visit rates were observed both pre- and post-implantation among females (RR 1.13 vs 1.14), older adults (RR 1.06 vs 1.15), individuals needing assistance with daily activities (RR 1.11 vs 1.12), individuals with chronic health conditions (RR 1.25 vs 1.34), with ≥6 RxRisk comorbidities (RR 2.35 vs 2.22) and adults residing in socio-economically disadvantaged areas (RR 1.64 vs 1.19). Mental health conditions were associated with increased specialist visits pre- and post-implantation (RR 2.57 vs 2.53), while employed individuals had higher specialist visit rates post-implantation (RR 1.58). Average OOP costs for health services decreased by 31.4% post-implant. Government benefits were higher pre-implant (55.6%) than post-implant (44.4%). Females and adults needing assistance with activities of daily living were more likely to seek government benefits.

These findings highlight the need for tailored healthcare and social support services to address the diverse needs of cochlear implant users, ensuring comprehensive care and support throughout their healthcare journey.

Paediatric hospitalisation, encompassing the period from admission to discharge, often involves feelings of pain, fear and anxiety, primarily due to clinical diagnoses and, more significantly, discomfort and stress-inducing procedures. Numerous methodologies and interventions have been investigated and implemented to alleviate these phenomena during paediatric hospitalisation. Virtual reality (VR), for example, has demonstrated efficacy in pain relief for hospitalised children in recent studies. This systematic review, therefore, aims to identify and evaluate the effectiveness of VR in alleviating pain, fear and anxiety in hospitalised children undergoing painful procedures.

This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines. A systematic search will be conducted in March and April 2025 across the following databases, with no restrictions on language or publication year: PubMed, Embase, Scopus, Web of Science, Cumulated Index in Nursing and Allied Health Literature, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials. Eligible studies will include randomised and quasi-randomised clinical trials involving children (aged 2–10 years) and adolescents (aged 10–18 years) who received VR interventions during painful procedures. Data will be managed and analysed using Review Manager software (RevMan 5.2.3). In cases of significant heterogeneity (I² > 50%), a random-effects model will be employed to combine studies and calculate the OR with a 95% CI. The methodological quality of the included studies will be assessed using the Cochrane Risk of Bias 2.0 tool, and the certainty of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluations framework.

This study will solely review published data; thus, ethical approval is not required. This systematic review is expected to provide subsidies, evidence and insights into the use of VR. It is also anticipated that the results will directly impact the improvement of care for these patients and the qualification of professional care.

CRD42024568297.

Acute pain in the postoperative period of cardiac surgery is mostly treated with opioid analgesics. However, with the risk of adverse reactions and complications, strategies which do not involve opioid analgesics can be considered, such as aromatherapy. This systematic review aims to analyse the effectiveness of aromatherapy in relieving pain in post-cardiac surgery patients.

Two researchers will independently and simultaneously conduct searches and select studies from the following databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Literature on Health Sciences, Scopus, Web of Science, Cochrane (Library) and clinical trial registries (clinicaltrials.com), with no language or publication date restrictions. Randomised and quasi-randomised clinical trials on the use of aromatherapy for pain relief in postcardiac surgery patients will be included. Then, two researchers will independently examine the studies based on inclusion criteria, extract data from the included studies and assess the risk of bias using the Risk of Bias 2 tool and the Risk of Bias in Non-randomized Studies of Interventions tool from Cochrane. Data will be synthesised using Review Manager software. The strength of the evidence will be evaluated using the Grading of Recommendation Assessment, Development and Evaluation approach. The literature search, study selection, review and meta-analysis stages will be conducted from early October 2025 to April 2026.

This study is based on secondary data, and therefore ethical approval from a research ethics committee was not required. The results will be disseminated through publication in a peer-reviewed scientific journal.

CRD42024568532.

Cluster analysis, a machine learning-based and data-driven technique for identifying groups in data, has demonstrated its potential in a wide range of contexts. However, critical appraisal and reproducibility are often limited by insufficient reporting, ultimately hampering the interpretation and trust of key stakeholders. The present paper describes the protocol that will guide the development of a reporting guideline and checklist for studies incorporating cluster analyses—Transparent Reporting of Cluster Analyses.

Following the recommended steps for developing reporting guidelines outlined by the Enhancing the QUAlity and Transparency Of health Research Network, the work will be divided into six stages. Stage 1: literature review to guide development of initial checklist. Stage 2: drafting of the initial checklist. Stage 3: internal revision of checklist. Stage 4: Delphi study in a global sample of researchers from varying fields (n=) to derive consensus regarding items in the checklist and piloting of the checklist. Stage 5: consensus meeting to consolidate checklist. Stage 6: production of statement paper and explanation and elaboration paper. Stage 7: dissemination via journals, conferences, social media and a dedicated web platform.

Due to local regulations, the planned study is exempt from the requirement of ethical review. The findings will be disseminated through peer-reviewed publications. The checklist with explanations will also be made available freely on a dedicated web platform (troca-statement.org) and in a repository.

Liver cirrhosis accounts for over 10 000 deaths in the UK each year with a total loss of 60 000 quality-adjusted life-years. There is a substantial cost to the NHS of £4.5 billion, with new liver-related decompensation events accounting for the majority of this. Following an acute cirrhosis decompensating event, there is a significant risk of hospital readmission with 90-day readmission rates as high as 53%. Current care in the UK is reactive and patients are often only readmitted when they have presented acutely as an emergency with significant decompensation.

CirrhoCare is a prospective, multicentre, randomised controlled trial comparing the CirrhoCare management system with standard-of-care for high-risk cirrhosis patients who have been discharged following an admission with acute decompensation. The CirrhoCare management system comprises a novel digital platform for use in a patient’s home, designed to proactively detect the first signs of new decompensation in patients with established cirrhosis, discharged to the community. This enables a clinician to instigate early community-based care or, if needed, to triage the patient for hospital interventions.

214 patients will be recruited to the CirrhoCare trial from at least 12 UK centres. Patients will be randomised on a 1:1 ratio allocation to the CirrhoCare Management System or standard of care. Participants who are randomised to CirrhoCare will receive a CirrhoCare health kit comprising a smart watch, smart phone with enabled SIM (Subscriber Identity Module) network card, blood pressure monitor, weighing scales and thermometer. Participants will take measurements every morning Monday to Friday and will be followed up for 90 days postdischarge.

The primary objective of this study is to assess the clinical effectiveness of the CirrhoCare digital management system. We hypothesise that its early community-based intervention will reduce the number of unplanned hospital interventions and admissions and prevent liver-related complications when compared with standard-of-care management.

CirrhoCare is a National Institute for Health and Care Research-funded study (NCT06223893). The study has UK Research Ethics Committee and Health Research Authority (HRA) approvals, with approval granted by the HRA and Health and Care Research Wales committee. The results of this study will be published in peer review journals, disseminated at international conferences as well as established Patient and Public Involvement and Engagement networks.

ISRCTN11380842.