To synthesise evidence from systematic reviews on difficult intravenous access (DIVA) in adults, focusing on definitions, diagnostic criteria, risk factors and clinical interventions to guide clinical practice and health policy.

Umbrella review of systematic reviews and meta-analyses.

Any clinical setting involving adult patients requiring peripheral venous access (including hospital, emergency and outpatient care).

A systematic search was performed in PubMed, CINAHL, Cochrane, Scopus and Web of Science in July 2025.

Systematic reviews and meta-analyses published from 2014 to 2025 that addressed DIVA in the adult population were included. Primary studies and protocols were excluded.

Methodological quality was assessed using the Risk Of Bias In Systematic Reviews tool. Data extraction followed the Joanna Briggs Institute methodology for overviews and the Preferred Reporting Items for Overviews of Reviews reporting guideline.

Seven reviews (six systematic reviews and one meta-analysis) were included. Three analytical dimensions emerged: (1) the conceptual and operational definition of DIVA, identifying common elements such as ≥2 failed attempts, lack of visible or palpable veins and a documented history of difficult access; (2) risk factors and clinical assessment, highlighting obesity, chronic diseases, prior chemotherapy, venous invisibility or non-palpability and the limited validation of diagnostic tools and (3) interventions, including organisational strategies (escalation protocols, specialised teams), technological resources (ultrasound guidance) and clinical measures (pain management and technique optimisation).

DIVA is a multifactorial challenge that requires a standardised definition to improve clinical identification. Effective management relies on a combination of specialised training, the use of ultrasound technology and the implementation of escalation protocols to ensure patient safety and efficiency.

CRD420251084947.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome associated with Alzheimer’s disease and frontotemporal degeneration. Non-invasive brain stimulation (NIBS) is a promising treatment, especially associated with language therapy, but comparative efficacy and long-term effects between the different techniques (transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS)) remain unknown. The present study aims to investigate the effects of non-invasive brain stimulation, alone or associated (tDCS/TMS/tDCS plus TMS) combined with language therapy delivered during a period of 6 months, in the progression of language impairment in PPA, compared with sham stimulation combined with language therapy.

The study is a randomised, double-blinded, parallel, sham-controlled clinical trial. Patients with PPA in early stages (global Clinical Dementia Rating equal to or less than 1) are eligible. They are to be randomised to one of the four treatment arms of the study (active tDCS-active TMS, active tDCS-sham TMS, sham tDCS-active TMS, sham tDCS-sham TMS). All patients will receive language therapy immediately after each session of NIBS, for 6 months. The primary outcome is the Mini-Linguistic State Examination. The secondary outcomes are naming of trained items, Addenbrooke’s Cognitive Examination, Interview for Deterioration in Daily Living Activities, Clinical Dementia Rating including behaviour and language domains, Neuropsychiatric Inventory and regional brain metabolism. Exploratory substudies will be conducted including blood biomarkers, quantitative electroencephalography and spontaneous speech assessment.

The study is registered (ClinicalTrials.gov: NCT07158216) and approved by the Ethics Committee of the Hospital Clinico San Carlos (code 25/309-IC_P_CE). Patients will be enrolled after signing an informed consent form. Study outcomes will be disseminated through presentations at scientific conferences, publications in peer-reviewed journals and other academic forums.

NCT07158216.

Integrated digital diagnostics can support complex surgeries in many anatomic sites, and brain tumour surgery represents one of the most complex cases. Neurosurgeons face several challenges during brain tumour surgeries, such as differentiating critical tissue from brain tumour margins. To overcome these challenges, the STRATUM project will develop a 3D decision support tool for brain surgery guidance and diagnostics based on multimodal data processing, including hyperspectral imaging, integrated as a point-of-care computing tool in neurosurgical workflows. This paper reports the protocol for the development and technical validation of the STRATUM tool.

This international multicentre, prospective, open, observational cohort study, STRATUM-OS (study: 28 months, pre-recruitment: 2 months, recruitment: 20 months, follow-up: 6 months), with no control group, will collect data from 320 patients undergoing standard neurosurgical procedures to: (1) develop and technically validate the STRATUM tool and (2) collect the outcome measures for comparing the standard procedure versus the standard procedure plus the use of the STRATUM tool during surgery in a subsequent historically controlled non-randomised clinical trial.

The protocol was approved by the participant ethics committees. Results will be disseminated in scientific conferences and peer-reviewed journals.

NCT07036783.

A synthesis and appraisal of the recommendations for biomarkers in practice guidelines concerning sepsis is required to consolidate evidence-based practice. We generated an evidence gap map (EGM) on the use of biomarkers for managing adults with sepsis.

Scoping review.

MEDLINE, Guidelines International Network, Pan American Health Organization, Trip Database and UpToDate were searched from 2016 to March 2025.

Guidance documents (GD) that searched at least one literature source and provided clinical recommendations for the use of biomarkers for the management (diagnosis and prognosis, including treatment response) of adults with sepsis.

Two reviewers independently applied the eligibility criteria and extracted data. We used the AGREE-II (Appraisal of Guidelines for Research and Evaluation) tool to assess the GD quality. GDs that scored ≥50% on the AGREE-II 'Rigour of development' domain were considered robust. We also applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate if the recommendations were strong or conditional.

We found 10 GDs, with only half (4/8) having a robust methodology. There were 31 recommendations concerning biomarkers. Among these, 24 (77.4%) recommendations were about single biomarkers, with lactate (23; 74.2%) and procalcitonin (8; 25.8%) most frequently recommended. Biomarker testing focused on prognosis in 28 (90.3%) recommendations. Overall, 16 (51.6%) recommendations were graded strong and 13 (42.0%) were conditional, which we displayed in an EGM.

The methodology of GDs concerning adult sepsis was poor. Our review calls for more prudent use of biomarkers in specific prognostic scenarios and in combination with standard clinical assessments. Enhancing the methodological quality of future GDs is essential to generate more valid and robust recommendations for optimising patient care.