Process evaluation provides insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a hybrid type 1 effectiveness-implementation randomised clinical trial of incremental-start haemodialysis (HD) versus conventional HD delivered to patients starting chronic dialysis (the TwoPlus Study). The trial will simultaneously assess the effectiveness of incremental-start HD in real-world settings and the implementation strategies needed to successfully integrate this intervention into routine practice. This manuscript describes the rationale and methods used to capture how incremental-start HD is implemented across settings and the factors influencing its implementation success or failure within this trial.

We will use the Consolidated Framework for Implementation Research (CFIR) and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks to inform process evaluation. Mixed methods include surveys conducted with treating providers (physicians) and dialysis personnel (nurses and dialysis administrators); semi-structured interviews with patient participants, caregivers of patient participants, treating providers (physicians and advanced practice practitioners), dialysis personnel (nurses, dieticians and social workers); and focus group meetings with study investigators and stakeholder partners. Data will be collected on the following implementation determinants: (a) organisational readiness to change, intervention acceptability and appropriateness; (b) inner setting characteristics underlying barriers and facilitators to the adoption of HD intervention at the enrollment centres; (c) external factors that mediate implementation; (d) adoption; (e) reach; (f) fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and (g) sustainability, to assess barriers and facilitators to maintaining intervention. Qualitative and quantitative data will be analysed iteratively and triangulated following a convergent parallel and pragmatic approach. Mixed methods analysis will use qualitative data to lend insight to quantitative findings. Process evaluation is important to understand factors influencing trial outcomes and identify potential contextual barriers and facilitators for the potential implementation of incremental-start HD into usual workflows in varied outpatient dialysis clinics and clinical practices. The process evaluation will help interpret and contextualise the trial clinical outcomes’ findings.

The study protocol was approved by the Wake Forest University School of Medicine Institutional Review Board (IRB). Findings from this study will be disseminated through peer-reviewed journals and scientific conferences.

NCT05828823.

Photobiomodulation (PBM) has shown promising effects in managing postoperative pain following conventional periapical surgery, although current evidence remains limited. This study aims to assess the effect of PBM on postoperative pain 24 hours after periapical surgery.

A randomised, controlled, double-blind trial will include 34 patients undergoing periapical surgery in the maxillary region, randomly assigned to an experimental group (n=17) or control group (n=17). The experimental group will receive PBM (GaAlAs diode laser, 808 nm, 100 mW, 4 J/cm², applied at five vestibular points) and placebo ibuprofen immediately and 24 hours postoperatively. The control group will receive simulated PBM and active ibuprofen. The primary outcome is postoperative pain assessed by the visual analogue scale at 24 hours. Secondary outcomes include pain at the seventh day, paracetamol intake, oedema, ecchymosis, soft tissue status and temperature at 24 hours and 7 days. Radiographic evaluation of healing will be performed at 1 and 3 months. Statistical analysis will be conducted based on data distribution, using repeated measures ANOVA (Analysis of Variance) or non-parametric equivalents for longitudinal outcomes, and appropriate tests for categorical variables. Significance will be set at p

The study was approved by the Human Research Ethics Committee of Universidad Católica del Uruguay (process no. 220914). Results will be disseminated to participants, healthcare professionals, the public and scientific communities.

NCT05935306.

Lynch syndrome (LS) carriers have a 20–46% lifetime risk of colorectal cancer (CRC) due to mismatch repair gene variants. Mesalamine (5-ASA, 5-aminosalicylic acid), used safely in patients with ulcerative colitis, may reduce CRC risk in LS by decreasing microsatellite instability, a key driver of LS-related cancer. This study evaluates 5-ASA’s efficacy as a tolerable chemopreventive drug, aiming to improve long-term CRC prevention in LS.

This multicentre, multinational, randomised, double-blind, two-arm, phase II clinical study will compare the effects of a 2-year daily intake of 5-ASA (2000 mg) to placebo in LS carriers. The primary objective is to assess whether mesalamine reduces colorectal neoplasia, both benign and malignant, compared with placebo in LS carriers, as detected by colonoscopy at the end of the treatment period (24 months±1 month) and on study completion. Secondary objectives include evaluating whether 5-ASA reduces neoplasia/tumour multiplicity and progression compared with placebo at specified time points, examining variations in the effects of 5-ASA versus placebo based on cancer history, sex and age (

The trial is currently open for enrolment, having received ethical approval from the Regional Ethical Review Board in Stockholm and funding from the Swedish Research Council. The study protocol is the finalised V.10.0 (11 April 2024), transitioned to the European Clinical Trials Information System. LS remains underdiagnosed, which may limit recruitment. The results are of global interest and will be published in peer-reviewed journals and presented at scientific conferences.

ClinicalTrials.gov: NCT04920149. EudraCT: 2019-003011-55. EU CT: 2024-514765-19-01.

Maternal respiratory syncytial virus (RSV) vaccination has been introduced to protect infants from severe respiratory infections. However, its uptake and impact on perinatal outcomes are unknown in the UK.

To evaluate uptake of RSV vaccine during pregnancy in a UK population.

This cross-sectional study was conducted at a tertiary maternity hospital in London. The participants included pregnant women who delivered between 1 September and 17 December 2024 (n=1157). For the analysis of vaccine uptake, the cohort included women eligible for vaccination who delivered beyond 28 weeks’ gestation and were at 36 weeks or less on 1 September 2024 (n=911). The main outcome measures were RSV vaccine uptake and its association with sociodemographic factors, perinatal outcomes including preterm birth (PTB), hypertensive disorders of pregnancy and stillbirth.

Of 911 eligible women, 19% (n=173) received the RSV vaccine during pregnancy. Uptake increased significantly from 4% in September to 32% in December (p

RSV vaccine uptake shows significant increases over time, with disparities in uptake by ethnicity and socioeconomic status. Further research is needed to increase vaccination rates, particularly in disadvantaged groups, and evaluate perinatal outcomes.

Transvaginal and transabdominal cerclage procedures have become established interventions to prevent mid-trimester pregnancy loss and preterm birth. Transabdominal cerclage seems to be superior to transvaginal cerclage in women with a history of a failed transvaginal cerclage. However, with the availability of a less invasive laparoscopic procedure, there is limited evidence concerning which type of cerclage to recommend to many other risk groups. The objective of this trial is to compare laparoscopic abdominal cerclage and transvaginal cerclage in women at moderate to high risk of spontaneous preterm birth.

The trial is an open, multicentre, superiority, parallel arm randomised controlled investigator-initiated trial with an embedded internal pilot. Women in whom the clinician has clinical equipoise between laparoscopic and transvaginal cerclage are randomised to either laparoscopic abdominal or transvaginal cerclage in a ratio of 1:1. The trial extends from sites in Denmark, Finland and Norway. The primary outcome is birth

The Central Denmark Region Committee on Biomedical Research Ethics, Denmark, Helsinki University Hospital Ethics committee, Finland and the Regional Committees for Medical and Health Research Ethics, Norway approved the trial. This protocol is published prior to complete data collection and analysis. Important protocol changes will be made publicly available on ClinicalTrials.org, on the trial website and distributed electronically to all active sites. Positive, inconclusive as well as negative results from the trial will be published in peer-reviewed international scientific journals.

NCT06122506.

Opioid agonist treatment (OAT) prescribing patterns have shifted in recent years in British Columbia (BC), Canada due to the increasingly toxic unregulated drug supply. Experimental evidence to support guidelines on the effectiveness of maintaining clients at different maintenance dosage levels is incomplete and outdated for the fentanyl era. Our objective is to assess the risk of treatment discontinuation and mortality among individuals receiving different maintenance dosage strategies for OAT with methadone, buprenorphine/naloxone or slow-release oral morphine (SROM) at the population level in BC, Canada.

We propose a retrospective population-level study of BC residents initiating OAT on methadone, buprenorphine/naloxone or SROM between 1 January 2010 and 31 December 2022 who were ≥18 years of age with no known pregnancy, no history of cancer diagnosis or receiving palliative care and not currently incarcerated. Our study will employ health administrative databases linked at the individual level to emulate a target trial per OAT type where individuals will be assigned to discrete maintenance dosing strategies, according to the full range observed in BC during the study period. Primary outcomes include treatment discontinuation and all-cause mortality. To determine the effectiveness of alternative maintenance doses, we will emulate a ‘per-protocol’ trial using a clone-censor-weight approach to adjust for measured time-dependent confounding by indication.

The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. All data are deidentified, securely stored and accessed in accordance with provincial privacy regulations. Results will be disseminated and shared with local advocacy groups and decision-makers, developers of national and international clinical guidelines, presented at national and international conferences and published in peer-reviewed journals electronically and in print.

Community health worker (CHW) interventions in control of HbA1c levels in diabetes have shown varied effects in randomised controlled trials. In the systematic review reported here, we aimed to evaluate the independent effectiveness of CHW interventions on the control of HbA1c levels in adults with type 2 diabetes.

Systematic review and meta-analysis.

1684 participants from 7 studies were included.

Randomised controlled trials of adults with type 2 diabetes receiving CHW interventions of at least 12 months’ duration compared with usual care were eligible. Databases searched were Ovid MEDLINE, the Cochrane Central Register, CINAHL and Web of Science from 2000 to March 2025. Quality was assessed using the Cochrane RoB2 tool.

Through meta-analysis, we calculated the mean weighted difference (MWD) of change in HbA1c level from baseline between groups using RevMan.

Seven of 86 retrieved studies were eligible. Six studies were suitable for meta-analysis and included 1280 participants. An inverse variance weighted meta-analysis showed a significant improvement in pooled HbA1c level with an MWD of 0.50% (0.28%, 0.71%) in the CHW group (p2=21%), and the overall level of certainty was high.

CHW interventions in type 2 diabetes showed statistically significant and clinically important reductions in HbA1c levels in people from minority ethnic groups on low income.

This study aimed to evaluate the utility of optical sensor-based technology in mitigating the frequency and severity of peripheral intravenous infiltration and/or extravasation (PIVIE) in neonates.

Single-centre, retrospective, observational cohort study.

Tertiary-level neonatal intensive care unit (NICU) (112 cots) at the Women’s Wellness and Research Centre (WWRC), Hamad Medical Corporation (HMC), Doha, Qatar, January 2019–December 2022.

All neonates admitted to the NICU requiring intravenous therapy via a neonatal short peripheral intravenous catheter (n-SPC) were included. Participants were excluded if the insertion was unsuccessful, if they had incomplete data, or if they received intravenous therapy exclusively through alternative vascular access devices.

The study analysed two cohorts representing different clinical practices over two distinct periods. In the conventional cohort (Phase 1, 2019–2020), PIVIE detection relied solely on periodic ‘Touch Look Compare (TLC)’ assessments. In the ivWatch cohort (Phase 2, 2021–2022), continuous optical sensor-based monitoring using the ivWatch system was implemented alongside TLC assessments. This sequential design allowed for a comparison of outcomes between the two phases.

The primary outcomes were the occurrence and severity of PIVIE. Secondary outcomes included the influence of patient demographics, vascular access characteristics, and management details on PIVIE incidence and severity.

Over the 4-year data collection period, 32 713 peripheral intravenous catheters were analysed across two cohorts. PIVIE was the most common reason for unplanned device removal. In the conventional cohort (Phase 1, 2019–2020), 4941 infiltration events were reported (29.9%), compared with 4872 events (30.1%) in the ivWatch cohort (Phase 2, 2021–2022). However, severity measures using the Intravenous Extravasation Grading Scale (IEGS) revealed a marked reduction in severe PIVIE cases, with severe events decreasing from 243 (4.9%) in the conventional cohort to 54 (1.1%) in the ivWatch cohort (p

PIVIE remains a frequent complication in neonatal vascular access. Continuous site monitoring with optical sensor technology was associated with earlier detection of PIVIE events and reduced IEGS severity scores. These findings highlight the potential of integrating sensor-based monitoring with traditional observational methods to improve patient outcomes in neonatal care.