Streptococcus pneumoniae serotype 3 (SPN3) remains a significant contributor to invasive pneumococcal disease globally, despite its inclusion in widely administered vaccines. The next generation of pneumococcal vaccines may confer better protection against this serotype, reducing disease burden. We describe an ethically approved protocol for a double-blind randomised controlled trial assessing the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine (PCV15)) and 0.9% saline (placebo) on the acquisition, density and duration of SPN3 carriage using a controlled human infection model.
Healthy adults aged 18–50 years will be randomised 1:1 to receive PCV15 or placebo. Participants will be considered enrolled on the trial at vaccination. One month following vaccination, all participants will be intranasally inoculated with SPN3. Following inoculation, participants will be followed up on days 2, 7, 14 and 28 to monitor safety, SPN3 colonisation status, density and duration, as well as immune responses. The primary endpoint of the study is to assess the rate of SPN3 acquisition between vaccinated and unvaccinated participants defined by classical microbiological methods. Secondary endpoints will determine the density and duration of SPN3 colonisation and compare the immune responses between study groups. An exploratory cohort of 5 participants will be asked to consent to a nasal biopsy procedure during a screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will only receive PCV15 and will not be challenged. Through this exploratory cohort, we will explore gene expression changes induced by PCV15 vaccination and their visualisation (spatial location) within the nasal tissue.
This protocol has been reviewed by the sponsor, funder and external peer reviewers. The study is approved by the NHS Research and Ethics Committee (Reference: 24/SC/0388) and by the Medicines and Healthcare Products Regulatory Agency (Reference: CTA 21584/0485/001-0001).
Adolescent pregnancy is a global issue. Early childbearing is strongly linked to poverty and negative health outcomes, including increased neonatal death risk. This study explores spatial patterns of adolescent pregnancies and neonatal deaths and their association with socioeconomic characteristics.
This population-based study used spatial analysis techniques to investigate the geographical distribution of adolescent pregnancies, socioeconomic characteristics and neonatal mortality rate (NMR).
The 645 municipalities of State of Sao Paulo, Brazil.
All live births to mothers residing in the State of Sao Paulo, Brazil, between 2004 and 2020.
The socioeconomic indicators used were: municipal human development index and per capita income (PCI). Spatial patterns were assessed for spatial autocorrelation (Moran’s I, LISA), and smoothed using local Bayesian estimation. Spearman’s correlation was used to ascertain the relationship between the percentage of live births to adolescent mothers and socioeconomic indexes. This calculation was also undertaken between different maternal age groups of NMR.
The study analysed over 10 million live births, with 14.3% attributed to adolescent mothers. Spatial analysis revealed significant clustering of adolescent pregnancies, strongly associated with lower socioeconomic indicators. NMR also exhibited spatial clustering, particularly after smoothing. Statistically significant differences were observed in PCI medians between high–high and low–low clusters for adolescent births. High and low incidence areas of NMR, both in all maternal ages and stratified by adolescent and non-adolescent mothers, demonstrated considerable overlap.
The results indicated the existence of clustering areas of adolescent pregnancy and neonatal deaths and suggested that the prevalence of births to adolescent mothers is not distributed equally and is higher in lower socioeconomic developed areas.
This study aims to assess how implementing a checklist for managing extremely preterm or extremely low birth weight infants can reduce mortality rates and morbidities.
A quasi-experimental, before-and-after study.
Neonatal intensive care unit at Dr. Cipto Mangunkusumo National General Hospital, a national referral hospital in Indonesia.
86 infants were born at
Implementation of a modified Canberra Health Services extremely preterm-early management checklist during the initial management of extremely preterm or low birth weight infants, including humidified gas resuscitation, thermal management, early surfactant administration and standardised first-hour care protocols.
The primary outcome was the mortality rate. Secondary outcomes included comorbidities such as hypothermia, hypoglycaemia, acidosis, intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL) and retinopathy of prematurity (ROP).
A total of 86 extremely premature and/or extremely low birth weight infants were enrolled, 48 neonates prior to and 38 neonates after the use of the checklist. Baseline characteristics were comparable between groups (median gestational age 27 weeks in both groups, median birth weight 795 g vs 868.5 g, p=0.09). Mortality at discharge showed a non-significant reduction from 52.1% to 47.4% (p=0.664, 0.91, 95% CI 0.64 to 1.30). Significant reductions were observed in IVH (79.2% to 28.9%, p
Implementation of a systematic checklist was associated with significant reductions in IVH and ROP, though mortality reduction was not statistically significant. These findings suggest potential benefits of structured early care protocols, but the observational design limits causal inference.
For patients with perihilar cholangiocarcinoma (pCCA), surgical resection remains the sole treatment modality that can potentially result in cure. Unfortunately, the majority of patients present with unresectable tumours or are excluded from surgical treatment due to complications like cholangitis affecting their performance status. In the Netherlands, recommended first-line treatment for patients with unresectable pCCA is palliative chemotherapy with gemcitabine and cisplatin. This regimen yields an estimated median overall survival (OS) of 11.7–15.2 months, highlighting the urgent need for novel treatment options. The STRONG I trial, a phase I study in patients with unresectable pCCA, was completed in 2020. Its aim was to assess the feasibility and toxicity profile of adding stereotactic body radiation therapy (SBRT) to chemotherapy. SBRT, delivered in 15 fractions of 4.0 Gray (Gy), was considered to be feasible and safe, with no dose-limiting toxicity being observed. The 1-year local tumour control rate was 80% and the 1-year OS rate 100%, with maintenance of quality of life (QoL). These results encouraged us to initiate the STRONG II trial, aiming to investigate the efficacy of adding SBRT to chemotherapy in a larger patient cohort.
STRONG II is a single-arm, multicentre phase II study. Patients with non-metastatic unresectable pCCA (T1-4, N0-2) are eligible. A total of 30 patients will be enrolled in six academic centres in the Netherlands and two in Belgium. SBRT will be delivered in 15 fractions of 4.0–4.5 Gy. The primary endpoint is local tumour control, defined by Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1. Secondary endpoints include toxicity, biliary stent-related events, progression-free survival, OS and QoL using the EuroQoL five-dimensional, five-level (EQ-5D-5L) questionnaire, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and the EORTC Biliary Module (QLQ-BIL21). In addition, we will explore the predictive value of the peripheral immunological status (immune-related proteins and serum functional immunological status assay) and its dynamics in determining survival outcomes. For this explorative translational study, two blood samples will be collected, one before the start of chemotherapy and another after completing chemotherapy.
Approval of the study was obtained on 5 June 2024 by the Medical Ethics Review Committee of Erasmus Medical Center Rotterdam, the Netherlands (ID: NL86210.078.24). The anticipated time frame for patient enrolment is July 2024 to December 2027. The main study findings will be published in peer-reviewed medical journals, and presented at national and international conferences.
NCT06493734 (ClinicalTrials.gov).
Post-COVID-19 conditions (PCC) may include pulmonary sequelae, fatigue and other symptoms, but its mechanisms are not fully elucidated.
This study investigated the correlation between fatigue and the presence of pulmonary abnormalities in PCC patients with respiratory involvement 6–12 months after hospitalisation.
Cross-sectional study.
A tertiary hospital in Brazil.
315 patients, aged ≥18 years, were considered eligible based on SARS-CoV-2 infection confirmed by reverse transcription-PCR.
Pulmonary function tests (PFT), cardiopulmonary exercise tests (CPET), chest CT and hand grip were performed. The following scales were applied: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, Euroqol 5 Dimensions quality of life (EQ-5D) and Hospital Anxiety and Depression Scale (HADS). Participants were divided between the fatigue group (FACIT-F≤30) and the non-fatigue group (FACIT-F>30). For the statistical analysis, the primary outcome was the difference in the diffusing capacity of the lungs for carbon monoxide (DLCO) between groups. Considered secondary outcomes were differences in PFT, CPET, chest CT, hand grip, EQ-5D and HADS.
The fatigue group had 81 patients (25.7%) against 234 (74.3%). PFT and CPET showed no significant difference in DLCO and oxygen consumption peak values between groups. The fatigue group had a lower workload (mean 55.3±21.3 watts vs 66.5±23.2 watts, p=0.003), higher breathing reserve (median 41.9% (33.8–52.5) vs 37.7% (28.9–47.1), p=0.028) and lower prevalence of ground glass opacity (60.8% vs 77.7%, p=0.003) and reticulation (36.7% vs 54.9%, p=0.005) in chest CT. The fatigue group had higher anxiety (57% vs 24%, p
Fatigue in patients with PCC 6–12 months after hospitalisation is relatively common and had weak correlation with pulmonary disorders. Our results suggested fatigue could be strongly related with peripheral disorders such as reduced musculoskeletal strength or psychosocial limitations.
Surgical oncology patients often experience doubts and uncertainties in the preoperative and postoperative periods, which can be addressed remotely through telenursing. Expanding telenursing services could contribute to more comprehensive perioperative care. We conducted a scoping review to characterise these telenursing services, identify their outcome indicators and examine the content of the care delivered.
A scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) recommendations.
MEDLINE (PubMed), EMBASE, CINAHL, SCOPUS, Web of Science and Virtual Health Library (VHL), with searches performed up to 5 May 2025.
We included studies that implemented telenursing interventions in the preoperative or postoperative period in adult oncology patients.
Two independent reviewers used a standardised search to select and extract data from the included studies. Study characteristics were presented descriptively using absolute and relative frequencies, and the content of telenursing interventions was organised into a circular thematic matrix.
A total of 37 studies were included, published between 1996 and 2024, conducted in 12 countries and primarily focused on postoperative telenursing via telephone or video calls. Preoperative care focused on psychosocial support and guidance related to surgical preparation. Postoperative topics included surgical wound care; handling of devices such as drains, ostomy bags and catheters; instructions for returning to work and support groups for financial and social assistance. Outcome indicators were primarily related to care, including levels of anxiety, stress, depression and quality of life.
Oncologic surgical telenursing remains primarily focused on postoperative care and the delivery of personalised support. Reporting on the protocols used, frequency and duration of sessions, nurse training and profiles, integration with in-person care workflows and operational cost data could strengthen the knowledge base for perioperative telenursing in oncology.
COVID-19 in children is generally of short duration, but some may take longer to recover. This study investigated the time to symptom resolution following SARS-CoV-2 infection among children in a community setting on the outskirts of an urban centre in Brazil.
Prospective cohort study.
This is a community-based cohort of children living in Manguinhos, a favela in Rio de Janeiro. The cohort was followed through home visits and telephone monitoring of symptoms. The analysis focused on symptomatic children from this cohort with confirmed SARS-CoV-2 infection. Recovery time was defined as the interval between the first date with symptoms and the first date without symptoms following a positive SARS-CoV-2 test.
A total of 1276 children (boys and girls aged 2–
COVID-19 recovery time, assessed based on change points on the symptom persistence probability curve (Kaplan-Meier).
Among children who tested positive, 148 (60%) were symptomatic. The median recovery time was 11 days (IQR: 7–16). Two inflection points were identified on the Kaplan-Meier curve: days 16 and 34. Children who were ill during the Omicron wave took longer to recover. More boys became asymptomatic within the first 15 days; about 93% of girls recovered by day 33, and boys were more common among those who recovered in ≥34 days. Children aged 6–
Among children from a vulnerable area in Rio de Janeiro, recovery time was longer than that reported in other countries, with 9.5% of children experiencing persistent symptoms for more than 33 days. These findings are crucial for understanding the implications of COVID-19 in specific socioeconomic contexts and the dynamics of paediatric recovery in community settings.
Guidelines for symptomatic knee osteoarthritis (OA) dictate the initiation of conservative treatment (physical therapy, analgesics and intra-articular injections with corticosteroids) as a first line defence. When conservative treatment fails, the golden standard is invasive joint replacement surgery, but for a substantial group of patients who do not respond to the current conservative treatment, this is not (yet) indicated. The RADIOPHENOL study investigates if denervation of knee sensory (genicular) nerves can serve the gap between conservative and invasive treatment for younger patients and for patients who cannot undergo joint replacement surgery due to comorbid health conditions.
The RADIOPHENOL study is a multicentre unblinded randomised controlled trial with three parallel arms (1:1:1). In total, 192 patients with knee OA Kellgren-Lawrence grades 2–4 but not eligible for joint replacement according to the orthopaedic surgeon due to young age, old age and/or comorbidity or technical reasons are eligible and will be randomised to three groups of 64 patients. Group A: traditional radiofrequency ablation, group B: chemical neurolysis with phenol, group C: conservative medical management. Primary outcome is the Oxford Knee Score at 6 months. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index, knee pain by numeric rating scale, physical functionality, health-related quality of life, mental health, change in medication use, predictive value of a diagnostic block, procedure time, patient discomfort score during the intervention and adverse events.
The protocol (V.2.0, 15 May 2023), was approved by the Ethics Committee of Amsterdam UMC (NL83410.018.22 – METC2022.0890) on 31 July 2023. We aim to publish our results in international peer-reviewed journals.
ClinicalTrials.gov NCT06094660, including the WHO Trial Registration data set items. Registered on 20 October 2023, first patient enrolled on 27 November 2023.