Video-assisted thoracoscopic surgery (VATS) lobectomy is a commonly employed surgical technique for the management of operable early stage non-small cell lung cancer (NSCLC). This procedure, however, is dependent on the patient’s ability to tolerate surgery. In light of this, stereotactic ablative radiotherapy (SABR) has emerged as a viable alternative treatment strategy for patients who are inoperable or who refuse surgery. Considering the lack of randomised controlled trials and the increased risk of bias in observational cohort studies, this study protocol proposes an emulated target trial design to investigate the causal effect of SABR, in comparison to VATS, on overall survival in operable early stage NSCLC patients.

Data on NSCLC patients will be collected from routinely collected university hospital records linked with German cancer registry data. This study protocol was developed using the target trial methodology outlined by Hernan et al. The protocol establishes specific parameters for key trial components in order to mitigate bias in the analysis of observational data and to facilitate the calculation of causal estimands. The target trial design that would be emulated is a multicentre open-label two-parallel arm superiority randomised trial. Mediators and confounding variables were determined through the use of a directed acyclic graph. The statistical analysis aims to measure the per-protocol and intention to treat effect of SABR versus VATS within 3 months of diagnosis, on survival, through the difference in restricted mean survival times, using weighted non-parametric Kaplan-Meier curves.

The Ethics Committee of the Medical Faculty of Martin Luther University Halle-Wittenberg with an approved addendum with Dnr 2023–112 has approved this study. The study uses anonymised routinely collected hospital and cancer registry data in accordance with applicable data protection regulations. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

Patient decision aids (PtDAs) are effective interventions to support patient involvement in health decisions and have the potential to impact favourably on health inequities by reducing gender bias in clinical practice. The aim was to explore sex and gender reporting and differences in randomised controlled trials (RCTs) evaluating PtDAs for adults making treatment or screening decisions.

Secondary analysis of the Cochrane review of PtDAs of RCTs that reported sex and/or gender. The original review searched MEDLINE, Embase, PsychINFO and EBSCO from journal inception to March 2022. Two team members independently screened citations, extracted data and assessed risk of bias. For this secondary analysis, we only included primary outcomes from the original review. We assessed appropriate use of terminology for sex (biological attribute) and gender (social construct). When terms were used interchangeably, it was considered inaccurate. Findings were synthesised descriptively, and we used meta-analysis when two or more RCTs were conducted with females/women or males/men using similar outcome measures.

Informed values-choice congruence and the quality of the decision-making process (eg, knowledge, accurate risk perceptions, feeling informed, clear values, participation in decision making, undecided) and adverse events (eg, decision regret, emotional distress) by sex and gender.

Of 209 RCTs in the original review, 206 reported sex and/or gender, with 35 (17%) using accurate terminology. Of 206 RCTs, 70 were with females/women only, 27 males/men only, 12 analysed by sex/gender and 97 RCTs did not disaggregate findings by sex or gender. Meta-analysis comparing RCTs for females/women to usual care and RCTs for males/men only compared with usual care showed similar mean differences in knowledge scores (10.84 vs 9.38 out of 100; p=0.44). Males/men had significantly higher self-reported participation in decision making compared with females/women (RR 3.16 vs 0.95; p

In PtDA RCTs, sex and gender terms are used interchangeably and 6% analysed outcomes by sex or gender. Meta-analysis of males/men only given PtDAs showed higher self-reported decision making participation in clinical practice compared to usual care versus females/women only compared with usual care. Researchers must improve reporting sex and gender in PtDA RCTs to assess how it influences health inequities.

The study explored patient experiences of the Call for a Kit (CFAK) intervention, a community-based initiative designed to improve bowel cancer screening uptake and examined the mechanisms that may support participation among non-responders.

A convergent parallel mixed-methods design was employed, combining quantitative surveys and qualitative interviews.

The evaluation was conducted in general practices across Lancashire and South Cumbria, Northwest England, where CFAK clinics were delivered by an external health promotion team based within the Community Voluntary Services. These clinics target practices with low screening uptake.

A total of 113 CFAK attendees aged 54 and above, and who had missed their most recent screening invitation, completed a patient experience survey. 12 participants were purposively sampled for follow-up interviews.

Statistical analyses examined associations between patient experience and screening behaviours, including kit ordering and intention to complete the screening kit. Thematic analysis explored barriers and facilitators to participation, as well as experiences of CFAK clinics.

Patient experience scores were significantly higher among women than men and were positively associated with intention to complete the kit, though not with kit ordering. Qualitative findings indicated that CFAK addressed key barriers such as low awareness, confusion and emotional discomfort by providing personalised education, reassurance and culturally sensitive support. Participants particularly valued the relational aspects of the intervention, including the face-to-face delivery and communication in preferred languages.

CFAK clinics appear to enhance psychological capability and motivation for bowel screening by offering tailored, inclusive and supportive care. These findings highlight the value of patient-centred approaches in addressing inequalities in cancer screening and offer insights for the design of future community-based interventions.

Despite the availability of curative treatments, hepatitis C diagnosis and treatment coverage is suboptimal globally with few countries on track to achieve the WHO’s 2030 elimination targets. In 2022, an estimated 50 million people were living with hepatitis C, with 1 million new infections annually. Most people living with hepatitis C reside in low- and middle-income countries, and people who inject drugs are disproportionately affected by hepatitis C.

Continuing simplification of diagnostic pathways and treatment care models is required to improve linkage to care and reduce costs associated with hepatitis C treatment and cure.

This study is a multi-country non-randomised, quasi-experimental, prospective comparative two-arm trial. It aims to assess the feasibility of implementation, retention in hepatitis C care and achievement of cure and cost-effectiveness outcomes, comparing two simplified hepatitis C testing and treatment pathways.

Arm 1 is a standard simplified test and treat model of care following global guidance, and arm 2 is an innovative rapid, same-day treatment initiation model of care using a presumptive treatment approach based on shortened read-time of the point-of-care OraQuick hepatitis C antibody test result. Secondary outcomes include assessing the accuracy of the OraQuick hepatitis C antibody test in predicting viraemia and the acceptability of each pathway.

This study will be implemented in Armenia, Georgia and Tanzania. Treatment-naïve people who inject drugs aged over 18 years in each country will be eligible for enrolment.

Recruitment commenced in October 2024 in Armenia, June 2025 in Georgia and August 2025 in Tanzania and is anticipated to close by December 2026.

This trial has been reviewed by WHO Ethics Review Committee (ERC), Alfred Hospital Ethics Committee (Australia) and local country ERCs. Alongside journal publications and conferences, the results from this study will be disseminated through summary reports and workshops with key stakeholders and with communities of people affected by HCV through relevant organisations/networks, including the global Community Advisory Board (CAB). The study results will inform national scale-up of simplified care models and inform potential pathways for further simplification of care models, including the potential for one-step diagnostic pathways and same-day treatment in particular scenarios for the three study countries, and other low- and middle-income countries globally.

NCT06159504.

Target trial emulation (TTE) has emerged as a methodological framework to strengthen causal inference from observational health data when randomised controlled trials are infeasible. The credibility of TTE studies depends not only on rigorous design and transparent reporting, but also on their relevance and acceptability to patients and the public. Patient and public involvement and engagement (PPIE) has been shown to enhance the relevance, transparency and impact of health research by shaping research priorities, informing study design and ensuring outcomes reflect patient perspectives. However, the extent to which PPIE has been incorporated into TTE studies remains unclear. This scoping review aims to systematically map the use and reporting of PPIE in published TTE studies.

This review will follow the Joanna Briggs Institute methodology for scoping reviews and will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews checklist. We will search MEDLINE (Ovid) and Embase (Ovid) from January 2011 to present, limited to English-language publications. Eligible studies will be studies that self-identify as using the TTE framework and report empirical analyses of health outcomes using observational or trial data. We will exclude protocols, methodological or simulation-only studies, preprints, conference abstracts and grey literature. Three reviewers will independently screen titles and abstracts, and then full texts, with disagreements resolved by discussion or adjudication. Data extraction will include study characteristics and PPIE information guided by the Guidance for Reporting Involvement of Patients and the Public 2-Short Form checklist. Findings will be summarised using descriptive statistics, tables, figures and narrative synthesis.

Ethics approval is not required, as this review will use publicly available data. Results will be disseminated through a peer-reviewed publication and presented at conferences.

Alcohol use disorder and treatment-resistant depression (TRD) often co-occur, presenting a major clinical challenge with limited effective treatments. However, ketamine produces rapid antidepressant effects and has shown promise in reducing alcohol use, and acceptance and commitment therapy (ACT) can be effective for both substance use and mood disorders. This study explores the feasibility and acceptability of combining ACT with ketamine within the framework of the Montreal Model—a structured, integrative psychedelic ketamine therapy developed for severe TRD.

This study is a single-group, open-label feasibility trial at the Centre hospitalier de l'Université de Montréal (CHUM) Neuromodulation Ketamine Clinic in Montreal, Canada. 30 participants diagnosed with both alcohol use disorder and treatment-resistant depression will receive eight weekly in-person or virtual ACT sessions in addition to six intravenous ketamine infusions. The primary outcome is feasibility, assessed through study completion and protocol adherence. Secondary outcomes include recruitment rate, tolerability, safety, data completeness and healthcare resource use. Exploratory measures will examine changes in depressive symptoms, alcohol use and quality of life using validated tools. A subset of participants will participate in semistructured qualitative interviews to explore their experiences.

This study was approved by the ethics committee of the CHUM on 14 May 2025. The results of the trial, including primary and secondary outcomes, will be published in peer-reviewed scientific journals.

NCT06620276.

To assess whether a medical telephone helpline and the use of a computer-assisted structured triage tool led to a reduction in demand for acute and emergency care in hospital emergency departments (EDs) or other ambulatory out-of-hour (OOH) services.

We conducted an ecological study using secondary data on outpatient care.

The study was conducted in 10 out of 16 federal states of Germany.

The analysis was based on ambulatory claims data for the years 2016–2020 by 11 Associations of Statutory Health Insurance Physicians (ASHIPs) covering more than 64% of the total German population.

The evaluated intervention comprised two components. The first was the introduction of a 24/7 medical helpline (116117), established to assist individuals with medical concerns in accessing appropriate care. The second component was the introduction of the computer-assisted triage tool SmED (Strukturierte medizinische Ersteinschätzung in Deutschland, Structured medical initial assessment in Germany) to support call-takers by suggesting medically relevant questions to identify red flags and determine the urgency of treatment and a possible treatment facility. For the analysis, approximately 3 years before and 1 1/2 years during the intervention were considered.

Main outcome was the effect on acute and emergency care which was measured as the number of personal doctor-patient contacts (1) in EDs (ED cases, data of 10 ASHIPs could be considered) and (2) in EDs or other OOH services (ED and OOH cases, data of 11 ASHIPs could be considered).

The analysis was limited by legal changes mandating intervention components across all study sites—leading to a loss of control groups and delayed implementation—and the onset of the COVID-19 pandemic. Across all ASHIPs and counties, the number of calls to 116117 and the number of SmED assessments showed a negative association with the number of ED cases (total change: 295.0 cases to 224.5 cases per 100 000 inhabitants, 116117 calls: r=–0.04; 95% CI –0.04 to –0.035; p≤0.001, SmED: r=–0.15; 95% CI –0.35 to 0.05; p=0.138) as well as with the combined number of ED and OOH cases (total change: 516.4 cases to 400.3 cases per 100 000 inhabitants, 116117 calls: r=–0.02; 95% CI –0.03 to –0.001; p≤0.01, SmED: r=–0.58; 95% CI –0.98 to –0.19; p≤0.01). However, the association between the number of SmED assessments and ED cases was not statistically significant. Moreover, the magnitude and direction of effects varied across ASHIPs. Sensitivity analyses restricted to time periods preceding the onset of the COVID-19 pandemic showed a non-significant negative association for 116117 calls and a significant positive association for SmED assessments with both ED cases and combined ED and OOH cases (ED cases: 116117 calls: r=–0.001; 95% CI –0.019 to –0.018; p=0.928; SmED: r=0.37; 95% CI 0.29 to 0.45; p≤0.001; ED and OOH services cases: 116117 calls: r=–0.03; 95% CI –0.06 to 0.003; p=0.077; SmED: r=0.34; 95% CI 0.20 to 0.48; p≤0.001).

Our findings indicate a trend suggesting that implementation of a 24/7 medical helpline may reduce the demand for acute and emergency care at EDs and OOH services, although clear evidence is lacking. The impact of SmED use remains inconclusive. Further research should ideally incorporate data linkage and controls and assess the effectiveness and efficiency of the triage process, as well as the quality of subsequent care at the individual level.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders globally, affecting 11–13% of women during reproductive age. PCOS is associated with an elevated risk of reproductive, metabolic, endocrine and mental health features. While lifestyle changes are first-line treatment for managing PCOS, metformin is often recommended for individuals with a body mass index (BMI) ≥25 kg/m². The aim of the metformin use in polycystic ovary syndrome (MET-PCOS) trial is to determine whether a metformin dose of 1500 mg per day or 2250 mg per day is superior in managing biochemical and clinical outcomes in PCOS.

MET-PCOS is a double-blind randomised controlled trial with two arms. It will be carried out at the Reproductive Medicine Unit at Helsinki University Hospital, starting from November 2025. Participants aged 18–37 years with a BMI≥25 kg/m² meeting the updated 2023 Rotterdam criteria for a PCOS diagnosis will be included. The participants (n=184) will be allocated (1:1) to a metformin dose of 1500 mg or 2250 mg per day. Outcomes include anthropometry, metabolic outcomes, hyperandrogenism, polycystic ovary morphology, menstrual cyclicity, mental health and gastrointestinal adverse effects. Measurements for study endpoints will be undertaken at baseline, 14 and 26 weeks.

The Finnish Medicines Agency has authorised the clinical trial (FIMEA/2025/00755) and the Regional Committee Medical Research Ethics, Finland (T7323/2024) has approved the trial protocol. This study will guide care providers in selecting the ideal metformin dose for individuals with PCOS.

NCT07120815, EU trial number: 2023-509259-15-01.

Newborn bloodspot screening (NBS) is freely and universally available to babies born in Australia, with nearly 300 000 newborns screened each year. The NBS programme screens for approximately 30 conditions; however, there are hundreds of childhood conditions that could be treated if identified earlier and asymptomatically. Contemporary screening platforms have relied on mass spectrometry-based technologies, limiting surveillance to conditions with validated biomarkers detectable within the neonatal period. Advancements in metabolic techniques and genomics have expanded the range of conditions that could be detected. The NewbornsInSA research study will develop, validate and evaluate a novel multi-omic model of newborn screening, integrating metabolomic and genomic newborn screening as complementary methodologies.

Parents can opt in to additional NBS through NewbornsInSA during pregnancy or shortly after birth. One thousand prospectively recruited families will be offered genomic NBS by whole-genome sequencing, including analysis of a virtual gene panel of over 600 genes, and concurrent metabolomic screening. Clinically actionable pathogenic or likely pathogenic genetic variants will be reported to parents and whole genome sequencing data will be available on request for diagnostic reanalysis, if required later in life.

Acceptability of the NewbornsInSA programme will be evaluated through stakeholder engagement activities with healthcare professionals, members of the public and patient advocacy groups. Family experiences will be assessed using online surveys. The diagnostic yield, accuracy and the costs and consequences of the multi-omic NBS model will be assessed by comparison to standard-of-care NBS.

NewbornsInSA will investigate the acceptability, feasibility and cost-effectiveness of a multi-omic newborn screening model in a prospectively recruited South Australian population. We hypothesise that this approach will increase the number of conditions identified, reduce the time to diagnosis and facilitate earlier care with better outcomes for newborns with genetic conditions.

This research study has been ethically approved by the Women’s and Children’s Health Network Human Research Ethics Committee (2022/HRE00258 and 2023/HRE00236). Findings will be disseminated through peer-reviewed publication and conferences.

To examine which information sources medical specialists use to answer clinical questions in daily practice and to describe the relative frequency of use for each source.

Systematic review with narrative synthesis and meta-analysis.

Academic Search Premier, APA PsycINFO, CINAHL, Emcare, Cochrane Library, Web of Science, Embase and PubMed were searched for relevant studies published from 2000 to 1 June 2025.

We included peer-reviewed English-language studies reporting on the frequency of information source usage by medical specialists when addressing clinical questions. Studies reporting usage on a continuous (0–100%) scale were eligible for meta-analysis.

Two reviewers independently screened studies. Data were extracted by one reviewer and checked by a second. Study quality was assessed using the Quality Assessment tool with Diverse Studies tool. A narrative synthesis was conducted for studies that were not eligible for quantitative pooling to summarise patterns in information-seeking behaviour and reported barriers. A random-effects meta-analysis was performed for studies reporting continuous usage percentages and assessing at least four information sources. Sensitivity analyses were conducted using a leave-one-out approach. Potential publication bias was explored descriptively using funnel plots.

25 studies were included, of which 6 (with 8641 participants) were eligible for meta-analysis. The narrative synthesis of non-pooled studies showed a consistent reliance on standalone information sources and identified barriers to the use of aggregated sources. In the meta-analysis, digital databases such as PubMed were the most frequently used information source (74%, 95% CI 63% to 85%), followed by textbooks (71%, 95% CI 57% to 85%) and consultation with colleagues (43%, 95% CI 15% to 71%). Systematically aggregated sources, including clinical practice guidelines (38%, 95% CI 27% to 49%) and point-of-care websites (49%, 95% CI 17% to 81%), were used less frequently. Sensitivity analyses indicated that pooled estimates were generally robust, although results should be interpreted cautiously given methodological variability across studies.

Medical specialists predominantly rely on standalone information sources when addressing clinical questions, while systematically aggregated and interpreted sources such as clinical practice guidelines and point-of-care tools are used less frequently. These findings highlight the need to better understand and address barriers to the use of aggregated information sources in clinical practice.

CRD42022267431.

Informed consent is an essential component of surgical care; however, patients often struggle to fully understand procedures, associated risks and available alternatives. Factors such as preoperative anxiety, limited health literacy and the complexity of consent documents can further impair comprehension and information retention. The active informed consent (CIA) pathway, based on a Patient Educational Program that combines multimedia resources with a comprehension test, aims to enhance patient understanding, improve satisfaction and reduce medicolegal issues.

The study will be conducted as a multicentre, non-pharmacological, randomised controlled trial in three hospitals in the Emilia-Romagna region (Italy). A total of 300 patients undergoing elective complex spinal surgery or robotic radical prostatectomy will be enrolled and randomised (1:1) to the experimental arm or to the standard informed consent arm, using block randomisation stratified by centre. Outcomes will include patient satisfaction (Client Satisfaction Questionnaire), comprehension, psychological distress (Depression Anxiety Stress Scales), pain (Numeric Rating Scale), functional recovery (Oswestry Disability Index/International Prostate Symptom Score/International Consultation on Incontinence Questionnaire Short Form/International Index of Erectile Function) and medicolegal complaints. Assessments will be performed at baseline (T0), discharge (T1), 2 months (T2) and 6 months (T3), with extended monitoring of medicolegal outcomes for up to 5 years.

The study has been approved by the Regional Ethics Committee of Emilia-Romagna (protocol CIA21, V.1.3 dated 14 December 2022). Participation is voluntary and does not affect standard care. Results will be disseminated through peer-reviewed journals, conference presentations and communication with health authorities. If effective, the intervention may be implemented as a scalable model to improve patient empowerment and transparency in surgical consent.

NCT06059599.

Inflammation plays a central role in atherosclerosis development and subsequent cardiovascular complications, including heart attack and stroke. Patients with inflammatory conditions such as community-acquired pneumonia (CAP) present with an elevated risk of cardiovascular events, which is likely driven by unresolved systemic inflammation. Targeting this heightened inflammatory burden may present a novel therapeutic strategy to attenuate heart attack risk in CAP survivors. Icosapent ethyl (IPE), an omega-3 fatty acid, demonstrates both pro-resolving and cardioprotective properties. The Targeting Vascular Inflammation In Patients with CAP (TIN-CAP) trial aims to evaluate the efficacy of IPE in mitigating vascular inflammation in CAP survivors.

TIN-CAP is a multicentre, randomised, double-blind, placebo-controlled trial. Eligible adults diagnosed with CAP in hospital or the emergency department will complete baseline assessments within 14 days of diagnosis including ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT angiography, bloodwork and quality of life evaluation (EuroQol – 5 Dimensions (EQ-5D)). Participants will then be randomised 1:1 to receive IPE (4 g/day) or placebo for 6 months. Follow-up visits will occur at 30 days (bloodwork and EQ-5D only) and 6 months. The primary endpoint is the change in FDG uptake in the ascending aorta from baseline to 6 months between IPE and placebo groups. Secondary endpoints include FDG uptake in the bone marrow, spleen, lungs and other vasculature, in addition to major adverse cardiac events and quality of life assessments. An initial lead-in cohort of 18 patients will be enrolled to assess recruitment, imaging feasibility and IPE tolerability prior to full trial enrolment. These patients will remain blinded and will be included in the final analysis (Vanguard design).

The TIN-CAP trial has been approved provincially by the Clinical Trials Ontario Research Ethics Board (approval number: 5045). Participants will provide written informed consent prior to enrolment. Study findings will be disseminated through peer-reviewed publications and conference presentations.

NCT06710080.