Fibrosing interstitial lung disease (F-ILD) are a heterogeneous group of diseases with multiple subtypes. Both idiopathic pulmonary fibrosis and other ILDs associated with a risk of developing progressive pulmonary fibrosis (PPF) are subtypes of this category. A multidisciplinary team discussion, including a chest high-resolution CT (HRCT), is usually considered the gold standard for diagnosis of F-ILD. Repeated HRCT is one of several established methods to assess progression and thus development of PPF, but it is associated with substantial costs and radiation exposure. Thoracic ultrasound (TUS) and other ultrasound (US) methods have emerged as radiation-free methods for both diagnosing and monitoring disease severity in F-ILD. Yet, consistent knowledge on the use of different TUS- and US methods in patients with F-ILD is limited.

The LORD study is a prospective cohort study conducted in participants with F-ILD at a tertiary ILD centre in Denmark. Physiological testing and patient-related outcome measures, together with TUS- and US examinations, will be performed at inclusion, after 6 and 12 months. The correlations between these assessments will be evaluated. HRCT will be conducted between 3 months prior to and 1 month after baseline, and after 1 year. At least 34 participants will be included.

The protocol was approved by the Danish Data Protection Agency (journal number: 22/45135) and the Science Ethics Committee for the Region of Southern Denmark (journal number: S-20220036). Results will be published in peer-reviewed international journals and will be presented at an international congress.

NCT06844331.

Does a simulation-based training intervention with an artificial intelligence (AI) navigation system improve their clinical bronchoscopy performance? And can the AIs outcome measures be used to evaluate clinical performance?

Pre–postintervention study.

Odense University Hospital of Southern Denmark, pulmonary endoscopy suite.

Nine bronchoscopists (4 experienced, >500 bronchoscopies and 5 intermediates, 10–500 bronchoscopies).

Diagnostic completeness (DC), structured progress (SP), procedure time (PT) and procedure efficiency (DC/PT).

The primary outcome measures showed no statistically significant difference between the pre- and postintervention bronchoscopies DC: 53% versus 59%, p=0.16, SP: 29% versus 32%, p=0.35 and PT: 219 s versus 181 s, p=0.22. The experienced outperformed the intermediates regarding DC: 73% versus 43%, p

DC, SP and PT showed no statistically significant difference after a simulation-based training intervention. DC, SP and procedure efficiency differentiated between experienced and intermediate bronchoscopists and can be used to evaluate clinical bronchoscopy performance.

Visual Patient Predictive (VPP) is an AI-based extension of the Visual Patient Avatar (VPA) that integrates deep learning models to predict upcoming vital sign deviations and display them as dashed visual elements. By explicitly showing anticipated changes, the system aims to support level 3 situation awareness—the projection of future patient states. This multicentre simulation study will evaluate whether predictive algorithms and visualisations integrated into the VPA (resulting in VPP) improve clinicians’ ability to anticipate critical vital sign changes compared with conventional number-based and waveform-based monitoring and examine its effects on decision-making, confidence, workload and user acceptance.

This investigator-initiated, randomised, within-subjects crossover, computer-based simulation trial will be conducted at five academic centres in Switzerland, Germany and the United States. Medical professionals from anaesthesiology departments will complete scenario-based prediction tasks using both VPP (as the index test) and conventional monitoring (as the reference standard) in randomised order, with the same participant evaluating both modalities and the identical underlying clinical scenario used in each condition, following video-based training and a learnability test. The primary outcome is recall (true positive rate) of vital sign deviation predictions. Secondary outcomes include average lead time, precision, prediction confidence, number and correctness of proposed interventions, perceived workload (NASA-TLX) and qualitative usability feedback. Quantitative data will be analysed using a logistic generalised linear mixed model with random intercepts for centre and participant, and a random slope for the intervention effect. Qualitative interviews will undergo thematic analysis.

The leading ethics committee (Zurich, Switzerland; BASEC-Req-2023–00465) reviewed and approved the study protocol. Ethics committees at the other participating centres have obtained their respective approvals or waivers. Bonn: 2025–144-BO, Boston: 2025P000501, Heidelberg: S-376/2025, Munich: 2025–357 W-CB. As this simulation study involves only healthcare professionals performing prediction tasks based on simulated vital sign scenarios—without collection of patient data or any medically relevant personal data—it does not constitute human subjects research under applicable regulations. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

Health inequalities remain resistant to interventions that primarily target individual behaviour. Although systems approaches are increasingly promoted, their application in practice is often not well grounded in real-world settings. In this protocol paper, we present the approach we will take in an overarching project that synthesises the combined insights of four ongoing systems-based research projects on system-based approaches for reducing health inequalities in the Netherlands. By bringing together and comparing findings across diverse contexts, populations and interventions, we aim to generate an empirically grounded understanding of what works, for whom, in what contexts and why, and to derive actionable strategies for systemic change to reduce health inequalities.

We use a realist approach to synthesise insights from the four ongoing projects. The design involves four iterative steps: (1) Identifying cross-cutting themes from project proposals and literature, (2) Developing and refining context–mechanism–outcome (CMO) configurations through literature review and Slow Science meetings, (3) Engaging Critical Friends to co-develop actionable strategies and (4) Assessing and validating these strategies across diverse contexts. Iterative feedback loops ensure continuous refinement, integration of stakeholder perspectives and exploration of emergent challenges. This design enables theory-informed, practice-based strategies to support sustainable system change in reducing health inequalities.

Ethical approval for the four underlying projects has been obtained from the relevant institutional review boards, and the way their data is used for this overarching project falls within their approved scope. Dissemination will be ongoing and co-created with stakeholders, including policy briefs, factsheets, educational tools and academic publications, to support uptake of strategies for systems change.

This study investigated district-level variations in the impact of COVID-19 on maternal, neonatal and child healthcare (MNCH) service utilisation, delivery and health outcomes in Gauteng, one of the hardest-hit provinces in South Africa.

A cross-sectional quantitative study.

We collected District Health Information System data for MNCH services from all 493 public healthcare facilities across all five districts in Gauteng province. We applied simple linear regression to assess key performance indicators before (March 2019 to February 2020) and during (March 2020 to February 2021) the COVID-19 pandemic. A pooled multiple linear regression model compared the impact of the pandemic in each district with that of the Johannesburg reference district. The regression models followed the bootstrap approach. Analyses were performed in Stata V.17.0.

Regarding service utilisation, primary headcount under 5 years (n) significantly decreased in all five districts during COVID-19. The effect was greater in Johannesburg (–20 954.5, 95% CI –28 913.3 to –12 995.7; p

In Gauteng province, the COVID-19 pandemic caused a heterogeneous adverse impact on MNCH service utilisation, delivery and health outcomes across the districts. Recognising the geographical differences in the effects of outbreaks and pandemics is critically important for informed decision-making to support healthcare services recovery in affected areas and for planning against future crises.

Implementation of low-intensity, evidence-based psychological interventions can help meet the mental health and psychosocial needs of people with cancer, especially in low-resource settings where there is a dearth of mental health specialists. In this study, we will conduct a feasibility randomised controlled trial (RCT) of the stress management intervention Self-Help Plus, which has been translated and adapted to Vietnamese, vSH+, among people newly diagnosed with breast or gynaecological cancer in Viet Nam.

At six participating hospitals, individuals diagnosed with breast or gynaecologic cancer within the past year will be recruited, consented and randomised into either enhanced usual care (EUC) or EUC plus the vSH+ intervention, which consists of four sessions each lasting approximately 75 min. Quantitative surveys will be administered at three time points: enrolment/baseline (T0), after 6 weeks (T1) and after 4 months (T2). A qualitative evaluation component, which will include in-depth interviews with patients, implementers and healthcare staff and managers, as well as focus group discussions with caregivers, will assess the acceptability and feasibility of the vSH+ intervention.

Ethical reviews for the study were obtained from Boston University, Hanoi University of Public Health (HUPH) and all the participating hospital sites. On completion of data collection and analyses, the research team will prepare and submit abstracts to scientific conferences as well as manuscripts to peer-reviewed journals. We will also conduct dissemination events to report the trial results to relevant stakeholders.

NCT06398067.

To evaluate the accuracy of the arterial oxygen partial pressure/inspired oxygen fraction (PaO₂/FiO₂) ratio in predicting mortality among acute respiratory distress syndrome (ARDS) patients in Vietnam.

A retrospective observational study.

A central hospital in Vietnam.

Adult patients diagnosed with ARDS based on the Berlin definition and admitted to Bach Mai Hospital between August 2015 and August 2023. ARDS severity was converted from descriptive categories to the Berlin score, ranging from 1 (PaO₂/FiO₂>300 mm Hg) to 4 (PaO₂/FiO₂≤100 mm Hg).

All-cause hospital mortality.

Of 345 patients, 67.5% were male, and the median age was 55.0 years (IQR: 39.0–66.0). Hospital mortality was 61.2% (211/345). On the first day of admission, the PaO₂/FiO₂ ratio (areas under the receiver operating characteristic curves (AUROC): 0.585 (95% CI 0.522 to 0.649)) showed limited predictive ability for hospital mortality. Incorporating the PaO₂/FiO₂ ratio into the Berlin score did not substantially improve accuracy (AUROC: 0.578 (95% CI 0.516 to 0.641)). Both measures were less accurate than Sequential Organ Failure Assessment (SOFA) (AUROC: 0.650 (95% CI 0.590 to 0.711)), Acute Physiology and Chronic Health Evaluation II (APACHE II) (AUROC: 0.685 (95% CI 0.628 to 0.742)) and Confusion, Urea >7 mmol/L (20 mg/dL), Respiratory rate ≥30 breaths/min, Blood pressure (systolic 2/FiO₂ values (adjusted OR, AOR: 0.988 (95% CI 0.979 to 0.996)) were independently associated with lower mortality risk, while higher Berlin (AOR: 2.477 (95% CI 1.190 to 5.156)), SOFA (AOR: 1.278 (95% CI 1.102 to 1.482)), APACHE II (AOR: 1.236 (95% CI 1.108 to 1.379)) and CURB-65 (AOR: 7.142 (95% CI 2.581 to 19.763)) scores were associated with increased mortality risk.

In this study of ARDS patients in Vietnam, the PaO₂/FiO₂ ratio demonstrated limited discriminatory ability for hospital mortality, and incorporating it into the Berlin score did not meaningfully improve performance. While less accurate than SOFA, APACHE II and CURB-65 scores, the PaO₂/FiO₂ ratio and Berlin score remained independently associated with mortality risk. These findings should be interpreted cautiously, given the retrospective design, single-centre setting and potential selection bias; further validation in larger, multicentre studies is warranted.

Cardiovascular diseases, overweight, type 2 diabetes and chronic kidney disease increase the risk of cardiovascular events.

Glucagon-like peptide-1 analogues are recommended by the European Society of Cardiology and the American College of Cardiology to lower the risk of death and progression of cardiovascular disease in patients with cardiovascular disease and type 2 diabetes. Semaglutide, tirzepatide and liraglutide are approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of type 2 diabetes mellitus and overweight. CagriSema is currently not approved, but several phase III trials are ongoing.

No previous systematic review has investigated the effects of semaglutide, tirzepatide, CagriSema and liraglutide, which may not be disease-specific, on hard binary outcomes for all trial populations at increased risk of cardiovascular events.

We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index—Science) and clinical trial registries from their inception and onwards to identify relevant randomised trials. We expect to perform the literature search in December 2025. Two review authors will independently extract data and assess the risk of bias. We will include randomised trials assessing the effects of semaglutide, tirzepatide, CagriSema and/or liraglutide in participants with an increased risk of cardiovascular events. The primary outcome will be all-cause mortality. Secondary outcomes will be myocardial infarction, stroke and all-cause hospitalisation. Data will be synthesised by aggregate data meta-analyses, Trial Sequential Analyses and network meta-analysis, risk of bias will be assessed with Cochrane Risk of Bias tool V. 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations and the Confidence in Network Meta-Analysis approach.

This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.

CRD42024623312.

This study aimed to assess construct validity against commonly used patient-reported outcome measures (PROMs), test–retest reliability and responsiveness of seven Dutch-Flemish Patient-Reported Outcomes Measurement Information System (PROMIS) computerised adaptive testing (CATs) in Dutch adults with type 2 diabetes (T2D), and assess their acceptability in healthcare providers and people with T2D.

A cross-sectional observational study in people with T2D and qualitative study involving both people with T2D and healthcare professionals.

Participants with T2D were recruited from the ongoing Hoorn Diabetes Care System cohort in the West-Friesland area of the Netherlands. Additionally, people with T2D and advanced chronic kidney disease were recruited at the outpatient clinics of Amsterdam University Medical Centre and ‘Niercentrum aan de Amstel’, both in the Amsterdam area of the Netherlands. The healthcare professionals involved in the qualitative part were recruited at the Amsterdam University Medical Centre.

314 people with T2D (age 64.0±10.8 years, 63.7% men).

Participants completed seven PROMIS CATs (assessing (1) Physical Function, (2) Pain Interference, (3) Fatigue, (4) Sleep Disturbance, (5) Anxiety, (6) Depression and (7) Ability to Participate in Social Roles and Activities), and PROMs measuring similar constructs. After 2 weeks and 6 months, participants completed the CATs measures again, together with seven Global Rating Scales (GRS) on perceived change in each domain. Construct validity was assessed using Pearson’s correlations. Test–retest reliability was assessed by the intraclass correlation coefficient (ICC). Measurement error was assessed by the standard error of measurement (SEM) and minimal detectable change (MDC). Responsiveness was assessed by correlations between change scores on the PROMIS CAT and GRS. Acceptability was assessed through focus groups and interviews in healthcare providers and people with T2D.

Except for Fatigue, all PROMIS CAT domains demonstrated sufficient construct validity, since ≥75% of the results was in accordance with a priori hypotheses. All seven PROMIS CATs showed sufficient test–retest reliability (ICCs 0.73–0.91). SEM and MDC ranged from 2.1 to 2.7 and from 5.7 to 7.4, respectively. Responsiveness was rated as insufficient in this study design as there was almost no change in participants’ own rating of their health compared with 6 months ago according to a global rating of change.

During the focus groups and interviews, healthcare providers and people with T2D agreed that CATs could serve as a conversation starter in routine care, but should never replace personal consultations with a doctor. If implemented, participants would be willing to spend 15 min to complete the PROMIS CATs.

The PROMIS CATs showed sufficient construct validity and test–retest reliability in most domains in people with T2D. Responsiveness needs to be evaluated in a population with poorer diabetes control or in a study design with longer follow-up. The CATs are well accepted to be used in care to identify relevant topics, but should not replace personal contact with the doctor.

Post-traumatic neck pain is common, representing a substantial human and societal burden. About 15%–25% of individuals involved in an accident causing whiplash continue to experience moderate-to-severe symptoms and functional impairment 1 year post-trauma. Factors such as age, high pain intensity, hypersensitivity to pain and early post-traumatic hyperarousal are associated with persistent neck pain. However, multiple questions remain unanswered regarding how best to improve early care. As such, research on recovery patterns (including indicators for health economic burden) and their predictors is still needed, including biomarkers for pre-traumatic and peri-traumatic stress, and the value of early prediction tools.

This prospective cohort study will include 100 participants (≥18 years) suffering from post-traumatic neck pain sustained within 72 hours of an accident. At baseline (a combination of inclusion and 1 week assessment), eligible participants will undergo a thorough evaluation, including assessment of descriptive characteristics, self-reported variables (eg, pain, disability, sleep quality and post-traumatic stress), biomarkers (eg, heart rate variability (HRV) and hair cortisol) and clinical tests (eg, cervical range of motion). Follow-up will be conducted at 3, 6 and 12 months post-trauma. Further, register data (eg, data on labour market attachment) will be added for the period. Among other methods, a receiver operating characteristic (ROC) curve and multivariable regression analyses will be used to evaluate performance and associations of the prediction tools and their associations with measures of HRV.

The sample size calculation is based on previous studies, estimating that 15% of participants will develop moderate-to-severe ongoing symptoms. Using a conservative estimate, 64 participants are needed to achieve a statistical power of 90% with an expected area under the curve of 0.80. Accounting for a 25% loss to follow-up, 80 participants are required. For regression analysis, 100 participants will be included. The prediction tool will be validated using ROC analysis, sensitivity and specificity. Logistic regression models will be performed with and without biomarkers and pain sensitivity. Health economic costs will be compared across groups. Multivariable regression will examine the link between HRV and post-traumatic stress disorder, adjusting for confounders and a moderation analysis will assess hair cortisol as a potential moderator.

The study is approved by the Regional Committee on Health Research Ethics of Southern Denmark (S-20230037). Due to the acute nature of recruitment, the study design does not allow for a 24-hour reflection period; however, this approach has been approved by the Committee.

Study results will be published in peer-reviewed journals and disseminated through non-scientific outlets, including patient and professional publications, press releases and social media. If effective, workshops for clinicians will be organised. Results will be published regardless of outcome, with coauthorships following ICMJE guidelines.

NCT06176209.

Parkinson’s disease is a neurological disease with a rising incidence and prevalence. Patients with Parkinson’s disease may receive antipsychotics, for example, due to Parkinson’s disease psychosis. Parkinson’s disease psychosis is characterised by visual hallucinations and other psychotic symptoms. To date, no systematic review has evaluated the effects of antipsychotics in patients with Parkinson’s disease. Therefore, this review aims to assess the beneficial and harmful effects of antipsychotics for Parkinson’s disease.

This is a protocol for a systematic review. A search specialist will perform a search in major medical databases (eg, MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica database), CENTRAL (Cochrane Central Register of Controlled Trials)) and clinical trial registries. Published and unpublished randomised clinical trials comparing antipsychotics to any control (placebo, standard care or other antipsychotics) in patients with Parkinson’s disease will be included. Two review authors will independently extract data and conduct risk of bias assessments with the Cochrane Risk of Bias tool—V.2. Primary outcomes will be all-cause mortality, serious adverse events and significant falls. Secondary outcomes will be hospitalisations, non-serious adverse events, Unified Parkinson’s Disease Rating Scale total score and psychotic symptoms using any valid symptom scale. Data will be synthesised by aggregate meta-analysis, trial sequential analysis and network meta-analysis. Several subgroup analyses are planned. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by GRADE (Grading of Recommendations Assessment, Development and Evaluations) and CiNeMA (Confidence in Network Meta-Analysis) approach.

This protocol does not include results, and ethics approval is not required for the project. The findings from the systematic review will be published in international peer-reviewed scientific journals.

PROSPERO ID: CRD42025633985. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD42025633985.

To increase the sustainability of healthcare, clinical trials must assess the environmental impact of interventions alongside clinical outcomes. This should be guided by Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) extensions, which will be developed by The Implementing Climate and Environmental Outcomes in Trials Group. The objective of the scoping review is to describe the existing methods for reporting and measuring environmental outcomes in randomised trials. The results will be used to inform the future development of the SPIRIT and CONSORT extensions on environmental outcomes (SPIRIT-ICE and CONSORT-ICE).

This protocol outlines the methodology for a scoping review, which will be conducted in two distinct sections: (1) identifying any existing guidelines, reviews or methodological studies describing environmental impacts of interventions and (2) identifying how environmental outcomes are reported in randomised trial protocols and trial results. A search specialist will search major medical databases, reference lists of trial publications and clinical trial registries to identify relevant publications. Data from the included studies will be extracted independently by two review authors. Based on the results, a preliminary list of items for the SPIRIT and CONSORT extensions will be developed.

This study does not include any human participants, and ethics approval is not required according to the Declaration of Helsinki. The findings from the scoping review will be published in international peer-reviewed journals, and the findings will be used to inform the design of a Delphi survey of relevant stakeholders.

Registered with Open Science 28 of February 2025.

The WHO has declared climate change the defining public health challenge of the 21st century. Incorporating climate and environmental outcomes in randomised trials is essential for enhancing healthcare treatments’ sustainability and safeguarding global health. To implement such outcomes, it is necessary to establish a framework for unbiased and transparent planning and reporting. We aim to develop extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2025) and Consolidated Standards of Reporting Trials (CONSORT 2025) statements by introducing guidelines for reporting climate and environmental outcomes.

This is a protocol for SPIRIT and CONSORT extensions on reporting climate and environmental outcomes in randomised trials termed SPIRIT-Implementing Climate and Environmental (ICE) and CONSORT-ICE. The development of the extensions will consist of five phases: phase 1—project launch, phase 2—review of the literature, phase 3—Delphi survey, phase 4—consensus meeting and phase 5—dissemination and implementation. The phases are expected to overlap. The SPIRIT-ICE and CONSORT-ICE extensions will be developed in parallel. The extensions will guide researchers on how and what to report when assessing climate and environmental outcomes.

The protocol was submitted to the Danish Research Ethics Committees, Denmark in June 2025. Ethics approval is expected in September 2025. The SPIRIT and CONSORT extensions will be published in international peer-reviewed journals.

The gig economy is a promising arena to reduce unemployment and provide other benefits such as the opportunity to earn supplemental income. Like all other forms of work, the gig space also presents occupational health issues for those working in it. This proposed review is aimed at identifying and describing the common occupational health outcomes reported within this workforce; second, to examine the risk factors that contribute to the development of these health issues; and third, to assess the interventions and support systems currently in place to promote the occupational health of gig workers.

A systematic review will be undertaken according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (2009). A search from 2015 to 2025 will be conducted on four global databases (Web of Science, SCOPUS, Academic Source Complete and Business Source Complete). Only records in English, full text and peer-reviewed journal articles will be included. Book chapters, thesis, reports and systematic reviews will be excluded. The Joanna Briggs Institute Critical Appraisal Tools will be used to assess the methodological rigour of various studies prior to inclusion for the final analysis. The extracted data will be synthesised using a narrative synthesis approach, integrating findings from both quantitative and qualitative studies.

This research is exempt from ethics approval because the work will be carried out on published documents. We will disseminate this protocol in a related peer-reviewed journal.

CRD420250654059.

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.

The evidence for the optimal duration of psychotherapy for borderline personality disorder (BPD) is scarce. Two previous trials have compared different durations of psychotherapy. The first compared 6 months versus 12 months of dialectical behaviour therapy for BPD (the FASTER trial). The second compared 5 months versus 14 months of mentalisation-based therapy for BPD (the MBT-RCT trial). The primary objective of the present study will be to provide an individual patient data pooled analysis of two randomised clinical trials by combining the two short-term groups and the two long-term groups from the FASTER and MBT-RCT trials, thereby providing greater statistical power than the individual trials. Accordingly, we will evaluate the overall evidence on the effects of short-term versus long-term psychotherapy for BPD and investigate whether certain subgroups might benefit from short-term versus long-term psychotherapy.

An individual patient data pooled analysis of the FASTER trial and the MBT-RCT trial will be conducted. The primary outcome will be a composite of the proportion of participants with a suicide, a suicide attempt or a psychiatric hospitalisation. The secondary outcome will be the proportion of participants with self-harm. Exploratory outcomes will be BPD symptoms, symptom distress, level of functioning and quality of life. We will primarily assess outcomes at 15 months after randomisation for the FASTER trial and at 16 months after randomisation for the MBT-RCT trial. Predefined subgroups based on the design variables in the original trials will be tested for interaction with the intervention as follows: trial, sex (male compared with female), age (below or at 30 years compared with above 30 years) and baseline level of functioning (Global Assessment of Functioning baseline score at 0–49 compared with 50–100).

The statistical analyses will be performed on anonymised trial data that have already been approved by the respective ethical committees that originally assessed the included trials. The final analysis will be published in a peer-reviewed scientific journal and the results will be presented at national seminars and international conferences.

CRD42024612840.

Asthma is a leading cause of morbidity and healthcare use among children. Risk factors of childhood asthma include atopic predisposition and severe wheezing episodes caused by rhinovirus infection in early life. In children with first-time rhinovirus-induced wheezing, we aim to study the response of a short corticosteroid treatment to prevent recurrent wheezing and asthma.

This is a double-blind, randomised, placebo-controlled, phase IV, international multicentre trial involving eight sites in Norway, Sweden and Finland. Two hundred and eighty 3–23 months old steroid-naïve children are randomised 1:1 to receive oral dexamethasone (0.3 mg/kg/day) versus placebo in 3 days for their first wheezing episode and rhinovirus infection. Rhinovirus is diagnosed with multiplex PCR. The two co-primary outcomes are time to next physician-confirmed wheezing episode, and time to asthma, within 24 months from inclusion. Asthma is defined as fulfilment of the 2007 National Asthma Education and Prevention Program—criteria for initiating asthma controller medication in children aged 0–4 years. Primary interaction analyses are age, gender, atopic predisposition, risk genotypes and viral co-detection. The optimal cut-off on the rhinovirus genome load used to define a true rhinovirus infection will be assessed by exploring interactions between rhinovirus genomic loads and study drug on the co-primary outcomes. Secondary outcomes are number of wheezing episodes, duration and severity of each wheezing episode, bronchial hyperreactivity, quality of life and safety (height/weight development) at 24 months from inclusion.

Rhinovirus positive children with acute wheezing fulfilling inclusion and exclusion criteria are enrolled after informed consent from both caregivers. This trial has received ethical approval from all sites. Results will be submitted to Competent Authorities and disseminated via peer-reviewed publications and conferences within paediatrics and other relevant fields. If proven effective, findings may be implemented directly into paediatric clinical guidelines.

NCT03889743.

Time-lapse imaging (TLI) systems for embryo incubation and assessment are hypothesised to improve the success rates of in vitro fertilisation (IVF) treatment by providing undisturbed culture conditions for embryos and/or providing more information on embryo development (morphokinetic parameters) to improve predictive accuracy for embryo selection. Despite numerous aggregate meta-analyses showing uncertainty of benefit, IVF clinics globally continue to invest significant resources into this technology with little translation of evidence into guidelines or policy frameworks. This may be attributed to heterogeneity in participant populations and/or variations in the use of TLI, as highlighted in the aggregate meta-analyses.

Our research proposal for evidence synthesis using individual participant data meta-analysis will provide greater power than aggregate meta-analysis to detect differential treatment effects for effectiveness (live birth, clinical pregnancy) and safety (pregnancy loss, multiple births, congenital malformations) outcomes across three comparisons (overall effect, undisturbed culture and morphokinetic parameters). We will also analyse if there are specific subgroups of women who may benefit from the intervention and if variations in use of the intervention show any benefits. We have incorporated the results of the literature search used for the latest Cochrane review (7 January 2019) into this review and will include all the trials included therein. We will further update the literature search to include new evidence by searching the electronic databases MEDLINE, EMBASE, CINAHL and CENTRAL from 07/01/2019 to date, outcomes for all ongoing trials reported in the 2019 Cochrane review, trial registers for newer ongoing/completed trials and the citation lists of all the newly identified trials for any relevant references. The search strategy will include a combination of subject headings and text words relating to or describing the participants and the intervention, with no language restrictions. Two authors will independently screen the titles and abstracts, and full text of articles retrieved from the search, to finalise a list of trials suitable for inclusion in the review. We will include randomised controlled trials that assess TLI systems for either undisturbed culture and/or use of morphokinetic parameters for embryo selection in women having IVF/ICSI treatment using their own oocytes.

Ethical approval is not required for this study. We plan to disseminate the findings of the research to all stakeholders, including the National Institute for Health and Care Excellence and other international guideline development groups, through publication in peer-reviewed journals, presentation at conferences, newsletters, meetings and websites of the funders, fertility charities and patient support groups.

CRD42024564332.

Post-traumatic stress disorder (PTSD) constitutes a significant anxiety disorder that exerts substantial societal and familial impacts, while concurrently imposing an additional as well as a substantial burden on the healthcare system. Beyond the direct expenses incurred in its treatment, PTSD also gives rise to broader economic costs. The details of these costs in the UK are currently, we believe, unknown.

Our methodology was developed collaboratively with a collaborative advisory group of clinicians, patients, carers and other stakeholders. A comprehensive search strategy was devised to identify articles, including systematic reviews evaluating the economic costs linked to PTSD. We adhered to the National Institute for Health and Care Excellence checklist for economic evaluations. After applying our search strategy, the selected included papers were analysed to identify various cost categories contributing to the economic burden of PTSD.

PubMed, PsycInfo, PTSDpubs, EMBASE and Google Scholar were searched from January 1990 until January 2023; the search was revised and re-run in September 2024.

The articles must have been published originally in English and include a detailed evaluation of costs related to PTSD.

Two independent reviewers used standardised methods to search, screen and code included papers. After applying our search strategy, selected included papers were analysed to identify various cost categories contributing to the economic burden of PTSD. Detailed information on per-contact and per-session costs of healthcare variables was obtained at 2020/2021 prices. Additionally, with the advisory group, we ensured the validity of frequencies and unit cost figures associated with variables linked to PTSD. Further, indirect socio-economic costs arising from PTSD were computed.

By extrapolating from cost components identified, our findings indicate an average annual cost exceeding £14 780 per person. Given current 2020/2021 prevalence rates, this translates to an annual societal burden of £40 billion, a figure that does not encompass the many additional financial burdens stemming from PTSD, such as poor or inconsistent employment. This figure does not include the myriad intangible costs ranging from reduced quality of life to suicidality and countless other issues a person may suffer from as a result of PTSD. Finally, this number does not capture the breadth of impact, as it is difficult to quantify how the families, communities and social systems are adversely affected (both financially and otherwise) by the condition.

The economic and societal burden of PTSD in the UK is far greater than what extant research and common understanding indicate, as there is minimal awareness and information relating to indirect costs or ancillary effects such as discrimination, joblessness, substance use and other comorbidities. Ultimately, we found that there exists, conservatively, an annual excess societal burden of £40 billion, or approximately £14 780 per person. We demonstrated that PTSD is a significantly larger burden on society and individuals than estimated and that we are gravely underquantifying the cost of this increasingly prevalent condition.