Countries face challenges in maternal and newborn care (MNC) regarding costs, workforce and sustainability. Organising integrated care is increasingly seen as a way to address these challenges. The evidence on the optimal organisation of integrated MNC in order to improve outcomes is limited.
(1) To study associations between organisational elements of integrated care and maternal and neonatal health outcomes, experiences of women and professionals, healthcare costs and care processes and (2) to examine how the different dimensions of integrated care, as defined by the Rainbow Model of Integrated Care, are reflected in the literature addressing these organisational elements.
We included 288 papers and identified 23 organisational elements, grouped into 6 categories: personal continuity of care; interventions to improve interdisciplinary collaboration and coordination; care by a midwife; alternative payment models (non-fee-for-service); place of birth outside the obstetric unit and woman-centred care. Personal continuity, care by a midwife and births outside obstetric units were most consistently associated with improved maternal and newborn outcomes, positive experiences for women and professionals and potential cost savings, particularly where well-coordinated multidisciplinary care was established. Positive professional experiences of collaboration depended on clear roles, mutual trust and respectful interdisciplinary behaviour. Evidence on collaboration interventions and alternative payment models was inconclusive. Most studies emphasised clinical and professional aspects rather than organisational integration, with implementation barriers linked to prevailing biomedical system orientations.
Although the literature provides substantial evidence of organisational elements that contribute to improved outcomes, a significant gap remains in understanding how to overcome the barriers in sustainable implementation of these elements within healthcare systems. Interpreted through a systems and transition science lens, these findings suggest that strengthening integrated maternity care requires system-level changes aligning with WHO policy directions towards midwifery models of person-centred care.
Phasix mesh is a fully resorbable synthetic mesh for use in clean and contaminated ventral incisional hernia repairs. Long-term absorbable Phasix mesh appears to be a safe and promising device in incisional hernia repair, with low recurrence rates; however, data on long-term complications after surgery, particularly after the resorption period of the mesh, are scarce.
This protocol describes a study of several European registries on the use of a Phasix mesh in incisional hernia repair. The primary endpoint of the study is long-term complications at 2–5 year follow-up after mesh implantation, with secondary endpoints including hernia recurrence and complications during short-term follow-up.
Ethical approval was not required for this protocol as the study is based on anonymised registry data collected with prior patient consent in each registry. Each participating registry has its own ethical approval process, and this study will adhere to those regulations. The results will be disseminated through peer-reviewed publications and conference presentations.
Value-based healthcare (VBHC) strives to improve the healthcare system by focusing on value of care, that is, patient relevant outcomes relative to the costs for achieving these outcomes. Within VBHC, patient participation is crucial to identify patient relevant outcomes and value improvement potential. However, patient participation in VBHC initiatives remains limited. Therefore, we aimed to improve patient participation within VBHC teams with the ultimate aim to develop a practical guide for patient participation in VBHC.
An action research study.
This study was conducted in seven collaborating Dutch hospitals from March 2023 to November 2024.
Seven VBHC teams were selected to participate in the cyclical action research steps, that is, orientation, planning, implementation, and evaluation, in which patient participation was implemented or improved. These included the following patient groups: prostate cancer, vulnerable elderly, breast cancer, diabetes, maternity care, colorectal cancer and chronic kidney disease.
Both qualitative and quantitative data were collected. Qualitative data included observations and minutes of meetings with the intervention teams. Quantitative data included responses to the Public and Patient Engagement Evaluation Tool (PPEET) by multiple members of the intervention (n=7) and control teams (n=94) at three time points (T1=6 months, T2=12 months, T3=end of study). Qualitative data were thematically analysed and quantitative data were analysed descriptively. Finally, the data were triangulated to create an overview of lessons learnt in improving patient participation.
Patient participation goals varied across teams, leading to diverse actions, such as establishing a diabetes patient panel and distributing questionnaires to patients with colorectal cancer. PPEET results show that 71% of intervention team members reported that patient participation had an impact on the team’s outcomes compared with 44% in control teams (T3). Furthermore, 80% of the intervention team members initially wanted training in patient participation (T1), which dropped to 29% at T3. Overall, 22 lessons in improving patient participation in multidisciplinary project teams were identified and compiled into a practical guide.
The action research process improved the process and impact of patient participation in the intervention teams. Furthermore, the results indicate that the action research process enhanced the team members’ knowledge and skills on patient participation. The practical guide developed in this study can be used to support implementation of patient participation in VBHC.
Couples diagnosed with unexplained subfertility are advised to start mild ovarian hyperstimulation and intrauterine insemination (MOH-IUI) as a primary treatment. Natural feedback mechanisms and hormone release are affected by artificially stimulated cycles and induced ovulation. Additional luteal support could positively affect progesterone patterns in the luteal phase. The LUMO study evaluates whether the addition of exogenous progesterone in the luteal phase following MOH-IUI treatment cycle will improve pregnancy and live birth rates.
A multicentre randomised, double-blind, controlled trial will be conducted in Dutch fertility clinics, academic and non-academic hospitals. There are two treatment arms: group A progesterone luteal phase support; group B placebo, without crossover. All initiated MOH-IUI cycles within 6 months after randomisation are included (study period). Participants will start study medication, applying a daily dosage of 2dd 300 mg progesterone (Utrogestan) or 2dd 300 mg placebo in vaginal capsules on the second day after the IUI procedure. Treatment is continued until the onset of menstruation, a negative pregnancy test (IUI+14 days), a miscarriage or until 7 weeks of gestation in case of a viable pregnancy. Follow-up ends at 12 months after the end of study period (18 months after study randomisation). The primary outcome is cumulative pregnancy rate, achieved within 6 months after randomisation, leading to live birth. A total of 1008 patients (504 patients in each group) will be included.
The study was approved by the Central Committee on Research Involving Human Subjects on 30 January 2023. All participating sites have the approval of the local Board of Directors to participate in the LUMO study. An informed consent form will be signed by all participants. Study results will be presented at (inter)national conferences and published in peer-reviewed journals. It is expected that the results of this trial will be used to draft national guidelines on this issue.
The study is registered in the EU CTIS trial register (2022-501534-33-00), the Dutch trial registry (registration number: LTR 24508), ClinicalTrials.gov (NCT05080569) and the WHO registry (universal trial number: U1111-1280-9461).
Preventable hospital patient harm events disproportionally affect certain patient populations. For some, harm extends beyond physical injury to include cultural, emotional or spiritual impacts. While these disparities are linked to socio-demographics (eg, race, education), they are driven by structural factors (eg, procedures and policies). Patient safety monitoring systems (eg, incident reporting, patient concerns) were not originally designed to identify equity-related harms and may inadvertently obscure or reinforce the injustices they should address. This study will examine how equity is currently considered within hospital incident reporting and patient concerns systems across Canada and will identify opportunities to strengthen these systems’ responsiveness to inequities in patient safety.
This 3-year exploratory sequential mixed-method study began in September 2024. Phase one involves qualitative interviews with patient safety and equity leads, patients/families/caregivers and leaders of innovative initiatives to explore current practices, gaps and innovations in how equity-related factors are identified and addressed within incident reporting and patient concerns systems. Findings will inform Phase 2, a modified Delphi process with patient safety and equity experts and persons with lived experience of equity-related harm events to refine and reach consensus on key equity-promoting features, considerations and recommendations for these systems. In Phase 3, consensus items will be used to develop a national cross-sectional survey assessing the extent to which equity is integrated into hospital incident reporting and patient concerns systems in Canada. A patient advisory committee will inform data collection, interpretation of findings and dissemination.
Ethics approval has been received for Phase 1, with subsequent approvals to be sought for later phases. Dissemination plans include peer-reviewed publications, presentations at international conferences and knowledge exchange activities to inform patient engagement, the design of incident reporting and patient concerns systems and policy development.
Cardiovascular events (CVEs), in particular acute coronary syndrome (ACS), complicate the course of a significant number of patients hospitalised for community-acquired pneumonia (CAP) or influenza. Emerging evidence suggests that this increased risk of CVEs could be mitigated by the use of acetylsalicylic acid (aspirin). The ASCAP study investigates whether the addition of aspirin to standard therapy in hospitalised patients with moderate-to-severe CAP or influenza can reduce the incidence of CVEs.
The ASCAP study is a multicentre, double-blind, placebo-controlled randomised trial in 16 university and general hospitals in the Netherlands, in which patients are randomised to acetylsalicylic acid or matching placebo for 90 days. Eligible patients are adults hospitalised for moderate-to-severe CAP or influenza. Patients with antithrombotic or anticoagulant drugs, or those with contraindications for aspirin, are excluded. The primary outcome is the incidence of ACS up to day 180. Secondary outcomes include the incidence of 4-point major adverse cardiovascular events up to day 180, as well as the incidence of major bleeding and clinically relevant non-major bleeding events up to day 90, all-cause mortality up to day 180 and quality of life and societal costs up to day 180. Survival time will be analysed by the log-rank test, stratified for CAP and influenza, with a two-sided alpha of 0.05. Assuming an average baseline ACS risk of 7.5% over 180 days with up to 30% variation across strata, and a 60% hazard reduction due to aspirin, the required sample size to achieve 80% power is 760 patients. Currently, 114 patients are enrolled in the study.
This study is approved by the Medical Ethics Committee Amsterdam UMC (Amsterdam, The Netherlands) under reference number 2023.0741 and registered under EU trial number 2023-504553-12-01 in the EU portal CTIS (Clinical Trials Information System). Results of the study will be published in a peer-reviewed journal.
EU CTIS: 2023-504553-12-01.
Internationally, the vision of a ‘Digital Trustworthy Evidence Ecosystem’ is being pursued with clinical practice guidelines (CPGs) as one element of such a system. Consequently, CPGs and CPG repositories need to be digitalised.
The objective of this prospective, before-after study is to evaluate the impact of digitalising a quality-assured CPG registry using the international data format standard ‘Fast Healthcare Interoperability Resources’ (FHIR). This includes the architecture of the registry, the format of individual guidelines and application programming interfaces to import and export CPG content. The study is guided by a scoping review.
The primary outcome is the usability of the digitalised CPG registry and CPG content for different user groups comprising CPG developers, CPG administrators, health care professionals and patients—including at the point of care in in- and outpatient settings—and technical professionals as users of CPG content in digital applications.
For the before-after comparison, semi-quantitative (surveys) and qualitative (focus groups) methods are applied. All user groups will be involved in a baseline analysis to assess user expectations and technical requirements. According to the results, the digitalised guideline registry will be implemented. The intervention comprises the testing of the digitalised registry with guideline content by all user groups. Analysis of outcomes will include formative and summative evaluation. Final results and further research needs will be discussed in a World Café with all stakeholders.
The Ethics Committee of the Berlin chamber of physicians, in accordance with its code of conduct §15 section 1 (Eth-KB-24-11) confirmed that no ethical approval is needed for this study. The study is registered in the German Clinical Trials Registry (No: DRKS00034111). Results will be presented at national and international conferences, published in peer-reviewed journals and on the website of the funding institution.
German Clinical Trials Registry (No: DRKS00034111).
Subarachnoid haemorrhage (SAH) is relatively frequent, accounting for 5% of strokes and affects a young population. Arterial vasospasm is a frequent complication of SAH, with an estimated incidence as high as 70%. Vasospasm is responsible for cerebral ischaemia which in turn is potentially responsible for severe morbidity (neurological deficit, neuropsychiatric disorders), poor quality of life (institutionalisation, inability to return to work) and increased mortality. Treatment with intravenous milrinone, an arterial vasodilator, has been proposed, but no randomised controlled study exists. We hypothesised that an intravenous infusion of milrinone would improve the neurological recovery of patients with vasospasm following aneurysmal SAH at 3 months.
The MiVAR (Milrinone Infusion for VAsospam treatment in subarachnoid hemoRrhage) study is an investigator-initiated, phase III multicentre, randomised placebo-controlled, double-blinded, superiority trial evaluating the effect of intravenous milrinone versus placebo (saline), in patients with cerebral vasospasm following aneurysmal SAH. Patients will be included within 6 hours of the confirmation of vasospasm diagnosis by a CT angiography and randomised to receive either milrinone (initial bolus of 0.1 mg/kg over 30 min—max 10 mg—followed by a continuous infusion at 1 µg/kg/min rate for at least 48 hours) or placebo. Milrinone (or placebo) could be increased to 1.5 µg/kg/min. The dose is adapted according to the clinical and/or transcranial Doppler response. 360 patients are expected to be included. The primary endpoint is the proportion of patients with a good neurological outcome at 3 months, defined as a modified Rankin score ≤2, obtained through a centralised standardised telephone interview (done by a unique trained team). The study started in August 2020, and the expected final follow-up is the last quarter of 2025. Analyses of the intention-to-treat and per-protocol populations are planned.
The MiVAR trial protocol has been approved by an ethics committee (Comité de Protection des Personnes Ouest V), by the Agence Nationale de Sécurité du Médicament (ANSM, Number 160 828A-21, approval date 26 December 2019) and by the ‘Commission Nationale Informatique et Liberté’ (CNIL, decision DR-2020-076, approval date 21 February 2020). The study will be conducted according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The MiVAR study will be the first multicentre randomised study to evaluate the efficacy of intravenous milrinone in improving the neurological outcomes at 3 months in patients with vasospasm following aneurysmal SAH.
NCT04362527, EudractCT number 2019-002145-37.
First post-contrAst SubtracTed (FAST) MRI, an abbreviated breast MRI scan, has high sensitivity for sub-centimetre aggressive breast cancer and short acquisition and interpretation times. These attributes promise effective supplemental screening. Until now, FAST MRI research has focused on women above population-risk of breast cancer (high mammographic density or personal history). DYAMOND aims to define the population within the population-risk NHS Breast Screening Programme (NHSBSP) likely to benefit from FAST MRI. The study population is the 40% of screening clients aged 50–52 who have average mammographic density (BI-RADS (Breast Imaging Reporting and Data System) B) on their first screening mammogram. DYAMOND will answer whether sufficient numbers of breast cancers, missed by mammography, can be detected by FAST MRI to justify the inclusion of this group in a future randomised controlled trial.
Prospective, multicentre, diagnostic yield, single-arm study with an embedded qualitative sub-study: all recruited participants undergo a FAST MRI. An internal pilot will assess the willingness of sites and screening clients to participate in the study. Screening clients aged 50–52, with a clear first NHSBSP mammogram and BI-RADS B mammographic density (by automated measurement) will be invited to participate (recruitment target: 1000). The primary outcome is the number of additional cancers detected by FAST MRI (missed by screening mammography). A Fleming’s two-stage design will be used as this allows for early stopping after stage 1, to save participants, funding costs and time continuing to the end of the study if the question can be answered earlier.
The NHSBSP Research and Innovation Development Advisory Committee and the Yorkshire and Humber–Sheffield Research Ethics Committee (23/YH/0268, study ID (IRAS): 330059) approved this research protocol. Participation involves a two-stage informed consent process, enabling screening for eligibility through automated mammographic density measurement. Patients with breast cancer helped shape the study design and co-produced participant-facing documents. They will disseminate the results to the public in a clear and meaningful way. Results will be published with open access in international peer-reviewed scientific journals.
To estimate the frequency of antidiabetic prescriptions in type 2 diabetes mellitus (T2DM) in Spain and describe changes in prescription patterns between 2018–2022 and 2023-2024.
Observational study.
Patients from primary care centres newly diagnosed with T2DM in 2018–2022 and 2023–2024.
In each period, the prescription frequency of an antidiabetic medication at the diagnosis of T2DM was calculated and subsequently subdivided into monotherapy and combination therapy. The prescription frequency of the most common antidiabetic drugs was also calculated. Calculations were made for the entire group of subjects and stratified by sex and age (under 60 years and 60 years or older). Comparison of the frequencies between the two periods was performed using the chi-square test.
In 2018–2022 and 2023–2024, 78.4% and 88.9% of patients, respectively, were prescribed an antidiabetic medication. The prescription frequencies for monotherapy and combination therapy were 66.1% and 33.9% in the first period and 57.4% and 42.6% in the second. The prescription frequencies for metformin as monotherapy and combination therapy were 57.4% and 27.8% in the first period and 46.6% and 39.8% in the second. Prescribing metformin with sodium-glucose cotransporter-2 inhibitors (SGLT2i) and/or glucagon-like peptide receptor 1 agonists (GLP1a) was the most frequent combination therapy: 12.8% in 2018–2022 and 29.5% in 2023–2024. With a few exceptions, the prescribing pattern was similar by sex and age. The difference between the prescribing distributions in the two periods is significant.
Antidiabetic medication prescribing at the diagnosis of T2DM was high. Most prescriptions contained metformin. Monotherapy decreased in 2023–2024 compared with 2018–2022, while combination therapy increased due to increased prescriptions of metformin with SGLT2i and/or GLP1a.
Thanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis, health outcomes have improved. This paper evaluates the health system costs and the health-related quality of life implications of these guidelines.
A sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015.
Data for patients aged ≥16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months.
Patient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS) and the EuroQoL; healthcare costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life Years (QALYs) were calculated from the EQ-5D utility scores. Cost–utility analysis was performed using the NHS and Social Care perspective.
A total of 49 patients were included; 35 were treated within 48 hours, ‘early’ (median (IQR) 8.25 [3.7–20.5]) and 14 were treated after 48 hours ‘delayed’ (median (IQR) 93.9 [66.7–100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0–3) compared with 4 (29%) in the delayed group. According to GOS, 10 (29%) had a good recovery in the early treatment group, but only 1 (7%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p
This study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment.
Ischaemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively affects patient and graft outcomes. Anaesthetic conditioning (AC) refers to the use of anaesthetic agents to mitigate IRI. AC is particularly associated with volatile anaesthetic (VA) agents and to a lesser extent to intravenous agents like propofol. VA like sevoflurane interferes with many of the processes underlying IRI and exerts renal protective properties in various models of injury and inflammation. We hypothesise that a sevoflurane-based anaesthesia is able to induce AC and thereby reduce post-transplant renal injury, reflected in improved graft and patient outcome, compared with a propofol-based anaesthesia in transplant recipients of a deceased donor kidney.
Investigator-initiated, multicentre, randomised, controlled and prospective clinical trial with two parallel groups. The study will include 488 kidney transplant recipients from donation after brain death (DBD) or donation after circulatory death (DCD) donors. Participants are randomised in a 1:1 design to a sevoflurane (intervention) or propofol (control) group. The primary endpoint is the incidence of delayed graft function in recipients of DCD and DBD donor kidneys and/or 1-year biopsy-proven and treated acute rejection. Secondary endpoints include functional delayed graft function defined as failure of serum creatinine levels to decrease by at least 10% per day for three consecutive days; primary non-function is defined as a permanent lack of function of the allograft; length of hospital stay and postoperative complications of all kinds, estimated glomerular filtration rate at 1 week and 3 and 12 months calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; readmissions at 3 and 12 months, graft survival and all-cause mortality at 12 months.
The study is approved by the local ethical committees and national data security agencies. Results are expected to be published in 2025.
Muscle-invasive bladder cancer (MIBC) is an aggressive type of cancer. About 50% of patients will die from the disease within 5 years despite radical treatment. This implies that in many patients, the disease has already spread at the time of radical treatment, even though imaging shows no signs of metastasis. We hypothesise that the standard local staging method, transurethral resection of the bladder tumour (TURBT), is partly responsible for tumour cell spread. Furthermore, TURBT (and re-TURBT in many patients) contributes to a significant delay to definitive therapy. The aim of this randomised study is to determine whether multiparametric MRI (mpMRI) of the bladder, in combination with a single outpatient bladder tumour biopsy for histological confirmation, is a safer, faster, less costly and, therefore, more cost-effective diagnostic pathway than TURBT to detect or rule out MIBC.
BladParadigm is a two-arm multicentre randomised controlled trial (RCT) conducted in the Netherlands. Over a 3-year period, patients with clinically suspected MIBC without evidence of metastases will be recruited and randomised 1:1 to either TURBT or 3-Tesla mpMRI with same-day outpatient bladder biopsy. The Vesical Imaging Reporting and Data System (VI-RADS) will be used to standardise mpMRI reporting. Patients will undergo definitive treatment based on the results of the TURBT or mpMRI. The study is powered to demonstrate that the mpMRI-based strategy is at least non-inferior to standard TURBT in patients treated with radical cystectomy alone, assuming a relative hazard of 0.55. The required sample size is 360 patients (180 TURBT, 180 mpMRI). The primary outcome is 2-year progression-free survival. Progression will be assessed by imaging, according to the current standard of care. Secondary outcome measures are time to definitive treatment, quality of life (EuroQol 5D-5L), healthcare costs and cost-effectiveness.
This study has received ethical approval from the Medical Ethical Committee Oost-Nederland (NL83685.091.23). All participants will provide written informed consent prior to inclusion. Findings of this study will be disseminated through peer-reviewed, open-access publications, presentations at scientific conferences and stakeholder briefings.
There remains little consensus or guidelines for the clinical management of traumatic orbital fractures (OFx). The OFx Registry aims to increase real-world clinical evidence for the treatment of OFx via prospective, multicentre, international data collection. The primary objectives of this observational cohort study are (1) to document current treatment practices for and (2) to assess the outcomes of surgical and non-surgical treatment of orbital floor and/or medial wall fractures.
Approximately 300 adult patients presenting with a displaced OFx in the orbital floor and/or medial wall will be enrolled prospectively over a recruitment period of ~36 months. All eligible patients treated either surgically or non-surgically as per routine standard of care will have follow-up assessments at 6 weeks, 3 months and 6 months post-treatment. Demographic data, injury details, treatment details and outcome measures will be documented in a cloud-based database. Outcome measures include clinical outcomes (eg, diplopia, extraocular motility, and condition of the eyelid, globe and soft tissues), radiological outcomes from collected images, patient-reported outcomes (eg, Diplopia Questionnaire and the newly developed AO Craniomaxillofacial (CMF) Injury Symptom Battery) and complications. A statistical analysis plan will be prepared before final analysis summarising the descriptive statistics to be used for data assessment. Appropriate research questions and statistical tests may be applied additionally, depending on the availability and quality of data collected.
Ethics approval was obtained before patients were enrolled at each participating site. Patient enrolment followed an informed consent process approved by the responsible ethics committee. Peer-reviewed publications are planned to disseminate the study results.
The SEV-IDF programme aims to track infants born before 33 weeks of gestation, with very low birth weight (VLBW), neonatal encephalopathy or severe birth anomalies and perinatal disease. It employs an open, prospective, multicentric, population-based cohort approach. This report aims to describe the methodology employed to establish and manage the programme, details regarding follow-up procedures, baseline characteristics of the included infants, and highlights new research opportunities emerging from the "Suivi des Enfants Vulnérables d'Ile-de-France" (SEV-IDF) programme.
The programme aims to (1) detect developmental anomalies early, (2) improve prevention using standardised data, (3) optimise follow-up care and (4) support multidisciplinary research.
Eligible participants are infants alive at discharge from the 59 maternities with a neonatal unit of the Île-de-France (IDF) region (France). A network of 567 trained physicians monitors the children’s development at 4 months, 1 and 2 years of corrected age, and 3, 4, 5, 6 and 7 years of age. Collected data include sociodemographic, pregnancy and neonatal characteristics, and standardised child development scores.
The programme enrolled 21 175 participants between 2016 and 2023, with 16 461 (77.7%) having a gestational age less than 33 weeks, 1916 (9.0%) others having VLBW, 1525 (7.2%) having encephalopathy and 1273 (6.0%) having another severe birth anomaly.
The collected data will enable the SEV-IDF scientific committee to describe high-risk infants in the IDF region, design evidence-based campaigns to improve the quality and effectiveness of the follow-up as well as conduct research on developmental anomalies in these high-risk infants. Ongoing research currently focuses on anticipating loss to follow-up and early detection of developmental anomalies.