Postoperative pain is common after surgery, with a high incidence and risk of becoming chronic. Current multimodal analgesia has drawbacks, including limited efficacy from single agents and opioid side effects and addiction risk. These issues have led to opioid-sparing multimodal analgesia. Transcutaneous auricular vagus nerve stimulation (taVNS) is non-invasive and convenient. Studies have shown it can reduce postoperative pain, improve mood and lower adverse events. However, taVNS lacks a comprehensive evaluation and standardised protocols, so further research is needed to provide reliable evidence.

This study strictly adheres to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. To identify suitable randomised controlled trials (RCTs), eight credible databases will be searched, including four English databases (Web of Science, PubMed, Cochrane Central Register of Controlled Trials, EMBASE) and four Chinese databases (China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Database, Chinese Biomedical Literature Database). RevMan V.5.3 will be employed to integrate the retrieved data and conduct meta-analyses. The methodological quality of included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. Additionally, the Grading of Recommendations, Assessment, Development and Evaluation system will be applied to assess the strength and certainty of the evidence. We will also conduct publication bias analyses, sensitivity analyses and subgroup analyses.

No ethical review is required as no private or confidential patient data will be included. Results of this study will be disseminated through a peer-reviewed journal.

CRD420251207651.

Acute respiratory distress syndrome (ARDS) is a major public health problem, accounting for 23% of intubated patients and associated with high mortality rates. Although lifesaving, invasive mechanical ventilation can worsen lung injury when ventilator settings are poorly adjusted to lung physiology. We hypothesise that individualising ventilator settings via (1) the bedside assessment of lung recruitability using a one-breath derecruitment manoeuvre and measurement of airway opening pressure to set positive end-expiratory pressure (PEEP), (2) controlling the distending pressure and (3) controlling respiratory drive improves ARDS outcomes.

The CAreful Ventilation In ARDS trial is an investigator-led multicentre (33 centres in eight countries), open-label, randomised controlled basket trial comparing two ventilation strategies in two subpopulations of moderate-to-severe ARDS: induced or not by COVID-19. A total of 740 patients will be randomised (370 in each substudy) in a 1:1 ratio to individualised ventilator settings or to using traditional PEEP to inspired fraction of oxygen tables for PEEP setting. Indications for proning and weaning strategies are similar in both arms. The primary outcome is all-cause mortality at day 60. Secondary outcomes include duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital stay, organ dysfunction, barotrauma and mortality in ICU, at day 28 and in hospital.

Ethics approval has been obtained for all participating centres: Unity Health Toronto Research Ethics Board (for three centres: St Michael’s Hospital, Toronto General Hospital and Toronto Western Hospital); Comité de Ética de Investigación con Medicamentos del Hospital Universitari Vall d’Hebron; Comité de protection des personnes Ile de France III; Comité d'Ética de la Investigatción con Medicamentos de la Fundació de Gestió Sanitària del Hospital de la Santa Creu i Sant Pau; Comitato Etico—Fondazione Policlinico Gemelli; Comitato Etico di Area Vasta Emilia Centro; NYU Langone Health Institutional Review Board; Comité Ético Científico de Ciencias de la Salud; Il Comitato Etico Area 1 dell’Azienda Ospedaliero-Universitaria ‘Ospedali Riuniti’ di Foggia; HIGA ‘Eva Perón’ Comité de Bioética; Comité de Revisión Institucional del Hospital Británico Comité de Ética en Investigación; Complejo Médico Churruca-Visca Comité de Ética Biomédica; Comité de Ética SATI Comité de Ética en Investigación; Comité de Ética en Investigación del CEMIC; Comité de Ética SATI Comité de Ética en Investigación; Medical Research Ethics Committees United. Findings will be disseminated in peer review journals and conference presentations.

NCT03963622.

Dyspnoea is an existentially burdensome symptom in patients with advanced and progressive diseases such as cancer, chronic obstructive pulmonary disease (COPD) and advanced heart failure. Recent studies have highlighted that symptomatic treatment of dyspnoea is often ineffective and may depend on the underlying disease. Immersive virtual reality (IVR) has emerged as a ‘digital therapeutic’ for conditions such as pain, anxiety, and dyspnoea. Brain functional MRI (fMRI) offers the opportunity to identify distinct patterns of dyspnoea. Current findings are mainly limited to healthy volunteers, but clinical data from patients with life-limiting conditions are needed. The aim of this study is to assess the feasibility of identifying dyspnoea patterns in different life-limiting conditions using fMRI and IVR.

This is an observational monocentric feasibility study, conducted in a tertiary university centre. Healthy volunteers and patients diagnosed with advanced cancer, COPD, or heart failure and suffering from persistent dyspnoea will undergo an fMRI of the brain using IVR. The primary outcome of feasibility will be evaluated using descriptive statistics. Secondary outcomes include analysis of fMRI patterns of dyspnoea across populations, patient-reported burden of participation, and correlation between dyspnoea and psychological symptoms. These preliminary data will help determine the sample size required for a future study evaluating differences in dyspnoea patterns. Exploratory comparison between the characteristics of all four groups will be assessed with Fisher’s test (for proportions) and either independent Student’s t-test or Mann-Whitney test, depending on distribution. Correlations between variables will be tested using the Pearson’s correlation coefficient. Statistical analysis will be performed using STATA.

This study protocol received ethical approval on 23 April 2025 from the Commission cantonale d’éthique de la recherche in the Canton of Geneva, Switzerland. The identification number is 2024-02289. Submission to peer-reviewed journals and presentation in international congresses for the dissemination of the study findings are planned.

Clinical Trials number is NCT07319039; Pre-results.

Approximately 6%–10% of adults carry food allergy labels. Many such labels are unverified and may be incorrect, contributing to delays in appropriate care, significant dietary restriction, anxiety and unnecessary use of emergency medications. Oral food challenges (OFCs) are the gold standard for confirming or excluding food allergy, but the current model of clinic-based challenges often has long wait times and logistical barriers. This study aims to investigate the feasibility and safety of home-based OFCs compared with standard in-clinic challenges in adults with negative skin-prick testing.

Food Challenge at HOme or in Medical Practice is a pilot multicentre randomised controlled trial enrolling 120 adults with reported food allergy labels and negative skin prick testing to the implicated food. Participants will be randomised 1:1 to undergo an OFC either at home or in-clinic. The study is designed to generate feasibility and preliminary safety data for home-based OFC, measured by the proportion of participants experiencing immune-mediated adverse events (AEs), compared with clinic-based OFC. Feasibility metrics (screening to recruitment ratio, protocol completion), non-immune AEs, protocol adherence and quality of life assessed using the Food Allergy Quality of Life Questionnaire-12 at baseline prior to OFC and 6 months post OFC will also be collected. Statistical analysis will include descriptive statistics, with comparisons between arms using risk differences and relative risks with 95% CIs.

The trial has received ethics approval from the Austin Health Human Research Ethics Committee (HREC/111750/Austin-2024). Findings will be disseminated through peer-reviewed publications and scientific meetings. Data will be presented in aggregated, de-identified form.

NCT06916819.

Higher levels of individual health literacy have been associated with better health outcomes, greater medication adherence and improved self-management of chronic conditions. Hence, higher health literacy levels are expected to be indirectly associated with lower healthcare costs. The aim of this review is to identify and synthesise available studies on the relationship between individual health literacy and healthcare costs.

Systematic review with qualitative evidence synthesis.

MEDLINE, Scopus, Web of Science Core Collection and CINAHL were searched up to 7 March 2025.

We considered only studies that investigated and quantified the relationship between individual health literacy and healthcare costs sustained by individuals, insurance companies or health providers.

Article screening and data extraction were performed by two authors independently. We critically appraised the identified study by using the AXIS checklist and evaluated the methodology adopted for cost analysis. Finally, we performed a qualitative synthesis of the study results.

Of a total of 5801 articles identified, 23 studies met the inclusion criteria. Almost half of the studies were conducted in the USA and about one-third in European countries. The included studies showed fair average quality and great heterogeneity in health literacy measures and cost analyses. The analyses considered general medical, treatment-related, inpatient, outpatient and emergency costs, out-of-pocket expenses and financial hardship. Fifteen studies reported statistically significant results, estimating the association between health literacy and costs or evaluating the difference in costs incurred by different health literacy subgroups. All study results supported the hypothesised negative association between health literacy levels and healthcare costs.

Individual health literacy was found to be negatively associated with a range of healthcare costs, although the supporting evidence was not always robust. Interventions aimed at containing healthcare expenditure should consider this association, while further research is needed to define its nature.

The review has been registered in the PROSPERO International prospective register of systematic reviews (registration code CRD42023435502).

China has continued to improve tuberculosis (TB) control in the past decade; however, the sudden outbreak of COVID-19 hindered this progress. As a province with a large population and frequent international exchanges, Guangdong has been seriously affected by COVID-19. This study aimed to understand the effect of COVID-19 on TB detection in Guangdong based on the autoregressive integrated moving average (ARIMA) model.

Time-series study.

Guangdong, China.

We used the ARIMA model to quantify the effect of COVID-19 by comparing reported cases during the COVID-19 pandemic with predicted cases under a counterfactual scenario of no COVID-19 pandemic. After model evaluation, we chose ARIMA (0,1,2)(0,1,1)₁₂ as the prediction model. We also highlighted that there were three emergency response periods in which the responses and public responses to COVID-19 varied.

During the pandemic period, the average annual TB notification rate was 57.95/100 000, which decreased by 27.97% compared with the pre-pandemic period. Although it decreased by 6.17% on average annually in the pre-pandemic period, it decreased by 14.92% in 2020 as compared with 2019, but only decreased by 0.34% in 2021 as compared with 2020. The results of the ARIMA model showed that the number of reported cases in 2020 decreased by 6.62% compared with that of the predicted cases, but this decreased by 0.42% only in 2021. The most seriously affected period was the second-level emergency response period in 2020, when the relative difference between reported and predicted cases reached the peak (–16.43%). The least affected period was the third-level emergency response period of 2021, the reported cases recovered and exceeded the predicted cases, with a gap of 0.77%.

TB detection in Guangdong had generally declined during the COVID-19 pandemic, which might be related to the movement restrictions, diverted resources and patients’ concerns. This decline would lead to the delay or even interruption of diagnosis and treatment, which would cause the regression of TB control. To improve TB detection, it is important for stakeholders to take consorted effort during public health emergencies.

To evaluate the psychometric properties of the Hospital Survey on Patient Safety Culture (HSoPSC) version 2.0 in Ethiopian public hospitals.

A cross-sectional study.

Five public hospitals in Eastern Ethiopia.

Healthcare professionals (N=582).

An adapted and contextualised version of HSoPSC 2.0 was used to conduct structural validity using exploratory and confirmatory factor analyses (EFA and CFA). Convergent and discriminant validity were evaluated through item loadings and interfactor correlations, respectively. Reliability was measured using McDonald’s omega and Cronbach’s alpha.

CFA indicated a poor model fit for the original 10-factor, 32-item HSoPSC 2.0 across all statistical indices: relative chi-square (²/df=7.71), root mean square error of approximation (RMSEA=0.108), standardised root mean square residual (SRMR=0.088), comparative fit index (CFI=0.814) and Tucker-Lewis’s index (TLI=0.780). Consequently, a comprehensive EFA was conducted, which identified a revised model comprising 5-factor, 21-item. This model accounted for 62.8% of the total variance and demonstrated strong construct validity, with excellent fit indices (²/df=3.67, RMSEA=0.068, SRMR=0.034, CFI=0.969, TLI=0.945). Internal consistency, assessed via McDonald’s omega and Cronbach’s alpha, exceeded the acceptable threshold of 0.70 across all dimensions, except for Response to Error (0.66). The convergent and discriminant validity of the new model was confirmed, ensuring an accurate representation of the underlying constructs.

The original HSoPSC 2.0 with 10-factor, 32-item failed to demonstrate structural validity in the Ethiopian healthcare context. In contrast, a revised 5-factor, 21-item model showed strong validity and acceptable reliability. This adapted version provides a culturally and contextually relevant tool for assessing patient safety culture in Ethiopian healthcare settings.

To assess the effects of behaviourally informed short message service (SMS) reminders on demand for human papillomavirus (HPV) immunisation.

Individually randomised, five-group, controlled parallel trial.

A country-wide trial in Georgia.

55 176 girls aged 10–12, the entire population of unvaccinated girls of this age in the country, for whom there existed caregiver contact details.

Girls were randomised into five arms (four with n=11 035, with one n=11 036). Caregivers of the girls in four of the arms (treatment groups) were sent different versions of an SMS reminder (SMSR), reminding them that the girl was due to receive the HPV vaccine. The control group was sent no SMSR.

The primary outcome was a girl’s HPV vaccination status at the end of the trial.

Girls and their caregivers were blinded to group assignment.

The number of participants analysed in the four treatment groups was 10,784, 10,802, 10,794 and 10,820, with 10 828 analysed in the control group.

Each of the SMSRs was more effective than the control (no reminder) in encouraging HPV vaccination. Girls whose caregiver(s) were sent version 3 had 65% greater odds of receiving the vaccine relative to the control group (OR=1.65; 95% CI 1.38 to 1.97). Among girls whose caregivers received version 1, version 2 and version 4 of the SMS, the odds of receiving the HPV vaccine were respectively 42% (OR=1.42; 95% CI 1.18 to 1.70), 34% (OR=1.34; 95% CI 1.12 to 1.61) and 35% (OR=1.35; 95% CI 1.13 to 1.62) higher compared with the girls in the control arm.

We find a positive and statistically significant effect for each version of the SMSR, relative to the control condition.

NCT05536674.

Leishmaniases are a group of vector-borne diseases caused by parasites of the genus Leishmania, which are renowned for increasing global spread due to factors like climate change, globalisation, urbanisation and migration. Leishmaniasis is classified as a neglected tropical disease but is endemic in several areas of the Mediterranean Basin, including Italy, where Leishmania infantum is most involved as the parasite, phlebotomine sand fly as the vector and dog as the principal reservoir. Effective surveillance of communicable infectious diseases is a goal worldwide for organisations such as the WHO and for local and national governments but is an unfulfilled objective. Even in Italy and particularly in the region of Tuscany, despite mandatory reporting, significant gaps each year are identified between reported cases and hospital admissions. By estimating the underreporting of confirmed human leishmaniasis cases, this protocol aims to suggest actions to strengthen the current epidemiological surveillance system to enable timely and effective public health intervention in human and veterinary populations.

This retrospective multicentre study, conducted in the Central Tuscany Health District, the most populous area of the Tuscany region with approximately 1.6 million inhabitants, is based on the analysis of data collected from 2014 to 2024 using diagnostic laboratory, hospital and regional information system sources. The primary objective is to estimate the degree of underreporting of leishmaniasis in this area through the application of capture-recapture models. The secondary objective is to analyse the clinical and demographic characteristics of individuals diagnosed as confirmed leishmaniasis cases between January 2014 and December 2024, as well as to perform a geolocation analysis of the cases. The study includes the entire population, both adult and paediatric, of the Central Tuscany Health District who underwent laboratory testing for leishmaniasis (serological tests identifying the presence of antibodies; parasitological examination with evidence of amastigotes in aspirates, smears or biopsy sections; culture examination of aspirates, biopsies and/or peripheral blood positive for the presence of promastigotes; identification of Leishmania nucleic acid in aspirates, biopsies and/or peripheral blood samples via molecular diagnosis).

The study is being conducted in accordance with the protocol approved by the Ethics Committee of the Tuscany Region – Pediatrics Section, in November 2024. Ethics Committee opinion register number: 219/2024. Because the study uses only pseudonymised, routinely collected administrative and laboratory data with no direct patient contact or intervention, individual informed consent was not required, as confirmed by the Ethics Committee. Findings will be submitted to a peer-reviewed journal, presented at international conferences and presented at stakeholder workshops.

Despite increasing proportions of underrepresented minority (URM) medical school graduates, their progression into surgical training and leadership remains disproportionately low. Barriers such as financial constraints, limited mentorship and implicit bias contribute to this disparity, creating a disconnect between the diversity of patient populations and those providing care. While interventions such as mentorship programmes and pipeline initiatives have been implemented, their overall effectiveness has not been systematically evaluated. The primary aim of this scoping review is to map the current landscape of interventions, programmes and policies designed to enhance access to surgical careers for URM learners.

Searches will be conducted on EMBASE, Web of Science and OVID MEDLINE. Three independent reviewers will screen references, extract data and perform analyses with disagreements adjudicated by a fourth reviewer. This review will include studies conducted across all levels of training: secondary (high school or secondary school), postsecondary (undergraduate, medical school) and postgraduate (residency, fellowship), with no geographical restrictions. The definition of URM will be accepted as reported within each individual study, allowing for variability in racial, ethnic, gender, socioeconomic or other criteria. The review will include any structured interventions, programmes or policies aimed at increasing URM representation in surgical education. Data on the nature, duration and target population of each intervention will be extracted. The primary outcome will be the reported impact of interventions on URM representation or participation in surgical education. Secondary outcomes will include characteristics of the study participants, definitions of URM status and any qualitative or quantitative evaluations of intervention effectiveness.

Research ethics approval is not required under University of Toronto policy. Study results will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Results will be disseminated to relevant stakeholders at conference presentation(s) and submitted for publication in a peer-reviewed journal.

To explore how patients with thyroid cancer (TC) experienced and perceived post-traumatic growth (PTG) during diagnosis and thyroid-stimulating hormone suppression therapy (TSHST).

This is a descriptive qualitative study with individual semistructured WeChat interviews from March to May 2022. Data were analysed using qualitative thematic analysis.

Oncology surgery department in general hospitals in China.

A total of 13 patients with TC who had undergone TSHST after surgery were recruited through purposive maximum variation sampling and interviewed.

Five themes emerged that described the coping process and change of accepting cancer-related trauma: (1) stress and transition; (2) inner reconstruction and insights; (3) behavioural regulation and self-realisation; (4) assessment and linkage of growth resources; and (5) changing trend of growth. During the process of disease diagnosis and TSHST, the respondents used supportive growth resources to achieve inner reconstruction and insights, leading to behavioural regulation and self-realisation. These three conditions are mutually influential, ultimately determining their transformation from stress to positive inner growth.

The experiences of PTG among patients with TC varied during the diagnosis and treatment stages. Their PTG experiences are individually heterogeneous. Their somatic symptoms and psychological burdens can interplay with and influence their PTG experiences. Psychological interventions based on different positive psychological characteristics among patients with TC are essential to address patients’ disease-related trauma and help them achieve PTG.

Conventional treatments, like immunosuppressants for systemic lupus erythematosus (SLE), are associated with many side effects. Transcutaneous vagus nerve stimulation (tVNS) emerges as a promising adjunctive therapy, potentially offering a more benign therapeutic avenue for patients with SLE. The increased number of clinical trials, including randomised clinical trials, highlights the importance of a systematic review and meta-analysis to evaluate the efficacy and safety of tVNS in treating SLE. Consequently, the aim of this systematic review and meta-analysis protocol is to synthesise the available evidence to elucidate the efficacy and safety of tVNS for the treatment of SLE.

Databases include PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, China National Knowledge Infrastructure, VIP Database and Chinese BioMedical Literature Database. Data selection, extraction and quality assessment by two independent reviewers. Fatigue is the primary outcome, and secondary outcomes include pain, quality of life, negative emotions, adverse events and measures of SLE disease activity. We will use instruments appropriate for each study type to assess the risk of bias. The credibility of evidence will be evaluated using the grading of recommendation, assessment, development and evaluation system. For meta-analysis, we will use RevMan software to perform data synthesis (V.5.4.1). Besides, publication bias assessment, sensitivity, subgroup and meta-regression analyses will be conducted as appropriate.

All data used in our study will be extracted from published clinical trials and, therefore, no ethical approval is required. Study results will be disseminated through peer-reviewed journals and relevant academic conferences.

PROSPERO CRD42024525580.