To reduce perinatal deaths, identification of their causes is paramount. 'The WHO application of ICD-10 to deaths during the perinatal period' (ICD-PM) was developed to improve the quality of perinatal death data. To determine stillbirth and very early neonatal death rates across 16 hospitals in Benin, Malawi, Tanzania, and Uganda, examine causes of death and associated maternal conditions applying the ICD-PM, and assess how a clinical perinatal e-registry performed when applying the ICD-PM. We used cross-sectional data collected between 1st July 2021 and 29th February 2024 of babies weighing ≥1000 g or ≥28 weeks of gestational age, born to women aged 13-50 years in the participating hospitals. After analyzing 143,105 births, the stillbirth rate was 36.9 per 1,000 births and very early neonatal death rate was 7.7 per 1,000 live births. Nine in ten antepartum stillbirths could not be assigned a cause of death. Among intrapartum stillbirths, the most common cause of death was 'disorders of fetal growth' and for very early neonatal death it was 'complications of intrapartum events'. The e-registry provided information to report on 17 out of the 24 ICD-PM categories. Collecting high-quality clinical data through an e-registry allowed the identification of a cause of death for most intrapartum stillbirths and very early neonatal deaths. A specifically designed clinical questionnaire and simple diagnostic procedures could enable the application of the ICD-PM in settings with limited diagnostic resources and high mortality rates. Main findings: After applying the International Classification of Diseases to Perinatal Mortality classification system to a clinical dataset, a cause of death or an associated maternal condition was established for the majority of perinatal deaths, while most intrapartum stillbirths were a consequence of disorders of fetal growth, complications of intrapartum events were the main cause of very early neonatal deaths.Added knowledge: This study reveals that collecting basic clinical information through a structured questionnaire in high-burden and resource-limited settings can support the application of the International Classification of Diseases to Perinatal Mortality.Global health impact for policy and action: This study highlights that despite revisions and updates are needed, the International Classification of Diseases to Perinatal Mortality is still a valuable instrument that could help better understand the pathways to perinatal death, thus contributing to the development of targeted prevention strategies.
Emergency medical services (EMS) staff worldwide have long been at risk of encountering violence and aggression (V&A) at work, including threats, verbal, physical and sexual assault, and on rare occasions, fatalities occur. Exposure to V&A can result in stress, fear and burnout. This is an international problem and EMS employers, trade unions and others are working towards tackling it. The aim of this research was to conduct an exploratory qualitative interview study of EMS staff focusing on experiences, perceptions and interpretations of V&A directed towards them. This study took place in 2022 in one UK ambulance service covering a population of three million people. Individual, one-to-one semi-structured interviews were conducted with EMS staff via a Voice over Internet Protocol. Data were thematically analysed drawing on evolved grounded theory methodology concepts. 10 EMS staff were interviewed, and the following categories emerged: Rusted, busted and inevitability of V&A in EMS environment, Tolerable or intolerable V&A in EMS, Gendered V&A and genderisation in EMS, Modifiable factors and harm reduction of V&A in EMS, Professional, ethical and clinical judgments of V&A in EMS and Sociocultural and system frustrations of V&A in EMS. The basic social process that emerged was one of Systemic frustration and gender-based V&A in EMS. Protecting EMS staff from V&A is complex and multifaceted, and we have conducted a thematic analysis drawing on evolved grounded theory concepts that proposes V&A in EMS may be borne out of, and sustained, by systemic frustration and gender-based issues. We draw on Dollard's et al (1939) frustration-aggression hypothesis and Kelly's 'Continuum of Violence' (1988). Experiences of sexual V&A revealed in our study, supported by a wider body of knowledge, lay bare a caring context of rampant gender-based V&A directed towards EMS staff by members of society, colleagues and within the context of a patriarchal EMS. Our study revealed how EMS has not effectively tackled V&A and the many sociocultural constructs within EMS. We advocate for purposeful efforts, further research and systemic interventions beyond punitive measures to tackle this issue.
To date, traditional primary care practices are often organized around the capacities of one or more physicians. New models of primary care practices involving other health professionals such as advanced practice nurses (APNs) require modified triage models for more adequate patient allocation. Therefore, a modified triage model was developed, informed by experts and reviewed by stakeholders. A convergent mixed-method design with four phases was employed. The study was conducted in Swiss primary care practices. Readiness for change of health professionals working in these primary care practices was surveyed. Triage was reviewed and modified according to expert recommendations, and its feasibility explored in two Delphi rounds with health professionals and stakeholders. Health professionals in primary care practices were interested in improving access to care. Observed triage continued to focus primarily on physicians. The modified triage model was viewed to be practicable, offering a potential way to support more systematic allocation of patients to physicians, APNs, and other health professionals depending on the reason for consultation. Drawing on international guidelines on triage in primary care practices, expert opinion on who seeks care in these practices, and review by stakeholders led to a modified triage model to include other health professionals than primary care physicians. This study did not involve patients but focused on triage in primary care practices. Hence, no trial registration was obtained. The number of people growing older and continuing to live at home with chronic and multiple diseases is increasing. However, less physicians operate in primary care practices in the community, thereby limiting necessary access to care. Among the many solutions to counteract these problems, advanced practice nurses (APNs) are installed at primary care practices. To ensure that the best health professional is made available to people with health problems, current triage needs to be modified. For this purpose, a mixed-method study was conducted with Swiss primary care practices employing APNs in Switzerland. Data were collected on interprofessional collaboration and triage in use. Data were collected on interprofessional collaboration and triage in use. Drawing on these results, a modified triage model was developed. Primary care physicians, APN, other health professionals, and stakeholders critically reviewed this modified triage model. The model may help primary care practices consider different health professionals more systematically when responding to patients’ reasons for consultation. Whether this approach improves access, waiting times, workload distribution, or quality of care requires evaluation in future implementation studies.
Cardiac surgery-associated acute kidney injury is a common and serious complication of cardiac surgery. Albumin solution is a commonly administered fluid in cardiac surgery patients; the role of albumin in preventing cardiac surgery-associated acute kidney injury is unclear. The objective of this systematic review and meta-analysis was to evaluate the impact of perioperative albumin compared with other fluid regimens on the risk of acute kidney injury in cardiac surgical patients undergoing cardiopulmonary bypass. A systematic search was performed of MEDLINE®, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases, and the Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and ISRCTN registries. Randomized trials of adult patients undergoing on-bypass cardiac surgery comparing albumin-containing solutions with any other fluid regimen given perioperatively were included. Trials comparing fluids used only for bypass priming were excluded. Data extraction, risk of bias, and certainty of evidence were assessed in duplicate by independent reviewers. A Bayesian framework was the primary statistical approach, with a secondary frequentist approach. The primary outcome was perioperative acute kidney injury, defined as the period from surgery until hospital discharge. Secondary outcomes were all-cause mortality at longest follow-up, intensive care unit length of stay, hospital length of stay, proportion of patients requiring renal replacement therapy postoperatively, duration of mechanical ventilation postoperatively, and duration of vasopressor support postoperatively. Fourteen randomized trials, including 3,304 adults, were included in the analysis. Seven trials contributed data to the primary outcome. Four trials had an overall low risk of bias across all domains and outcomes. The pooled estimated risk ratio for acute kidney injury with albumin solutions was 1.09 (95% credible interval 0.86 - 1.34, tau = 0.12; I2 = 31.5%), with a 18.3% posterior probability of reduced acute kidney injury. There were no significant subgroup effects or differences in secondary outcomes. Among patients undergoing on-bypass cardiac surgery, the use of albumin solutions is unlikely to reduce the risk of acute kidney injury. Other interventions need to be considered for this condition.
Extensive-stage small cell lung cancer (SCLC) carries a poor prognosis and has limited therapeutic options. The addition of immune-checkpoint inhibitors (ICIs) to platinum-etoposide (PE) chemotherapy has become an important first-line treatment strategy. However, the comparative benefits and harms of different first-line chemotherapy-based regimens, including ICI-containing combinations, remain unclear. To evaluate the comparative benefits and harms of immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4), plus chemotherapy and other relevant first-line systemic chemotherapy-based regimens, for the first-line systemic treatment of extensive-stage SCLC with a network meta-analysis; to rank the interventions according to their benefits and harms; and to explore the potential role of biomarkers or clinical factors, where data are available. We used CENTRAL, MEDLINE, and Embase, together with clinical trial registries, to identify studies that were included in the review. The latest search date was 12 December 2025. We included randomised controlled trials (RCTs) comparing first-line systemic chemotherapy-based regimens, including chemotherapy alone, chemotherapy combined with ICIs, and other relevant combination strategies, in adults (≥ 18 years) with previously untreated extensive-stage SCLC. Critical outcomes were overall survival (OS) and adverse events (AEs). These include any grade AEs, serious AEs, and grade ≥ 3 AEs. Important outcomes were progression-free survival (PFS), objective response rate (ORR), and health-related quality of life (HRQoL). We assessed the risk of bias using the Cochrane RoB 2 tool. We judged most studies to have low risk of bias or some concerns across key domains. Some concerns mainly related to measurement of the outcome in open-label trials and selection of the reported result where protocols or registry entries were unavailable or incomplete. The extent to which these limitations may have influenced the critical outcomes of OS and AEs remains uncertain. We synthesised results for each outcome using meta-analysis where possible, using a contrast-based random-effects network meta-analysis with a common heterogeneity parameter. For network meta-analysis, we assessed the certainty of the evidence using the GRADE approach, informed by the CINeMA framework. Fourteen RCTs were included, with 7541 participants contributing to the critical outcome of OS. The evidence network comprised a total of 17 treatment regimens. Most studies compared PE chemotherapy combined with ICIs targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1). Some trials evaluated additional immune-checkpoint pathways, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), or incorporated anti-angiogenic agents. For OS, based on a network meta-analysis of 14 studies (7541 participants), PE + benmelstobart + anlotinib reduced the hazard of death most compared with PE (hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.47 to 0.79; high-certainty evidence), followed by PE + serplulimab (HR 0.63, 95% CI 0.49 to 0.82), PE + durvalumab (HR 0.71, 95% CI 0.59 to 0.85), and PE + adebrelimab (HR 0.72, 95% CI 0.58 to 0.90). Several other regimens, including PE + tislelizumab, PE + atezolizumab, PE + pembrolizumab, PE + toripalimab, and PE + durvalumab + tremelimumab, also reduced the hazard of death compared with PE. For PFS, based on 14 studies (7541 participants), the largest reductions in the hazard of progression were with PE + benmelstobart + anlotinib (HR 0.32, 95% CI 0.25 to 0.40) and PE + anlotinib (HR 0.44, 95% CI 0.36 to 0.54; high-certainty evidence). Several other regimens, including PE + tislelizumab, PE + serplulimab, PE + toripalimab, PE + adebrelimab, PE + pembrolizumab, PE + atezolizumab, and PE + durvalumab, also reduced the hazard of progression compared with PE. For ORR, based on 14 studies (7385 participants), PE + benmelstobart + anlotinib (RR 1.22, 95% CI 1.09 to 1.35), PE + anlotinib (RR 1.22, 95% CI 1.09 to 1.35), PE + pembrolizumab (RR 1.14, 95% CI 1.00 to 1.31), and PE + serplulimab (RR 1.14, 95% CI 1.03 to 1.26) increased the ORR compared with PE (high-certainty evidence), whereas most other regimens showed little or no difference compared with PE. Safety profiles varied across regimens. For any AEs, based on 11 studies (6249 participants), the risk was higher with PE + serplulimab (RR 1.25, 95% CI 1.08 to 1.43; high-certainty evidence) and was also increased with PE + ipilimumab and PE + atezolizumab-based combinations. For serious AEs, based on 10 studies (4264 participants), several regimens showed higher risks compared with PE. The largest increases were with PE + tislelizumab (RR 1.75, 95% CI 1.25 to 2.45) and PE + durvalumab + tremelimumab (RR 1.42, 95% CI 1.14 to 1.77). Higher risks were also seen with PE + adebrelimab, PE + benmelstobart + anlotinib, PE + toripalimab, and PE + socazolimab. For grade ≥ 3 AEs, based on 12 studies (6446 participants), differences between most regimens and PE were small, with increases for PE + atezolizumab + tiragolumab, PE + durvalumab + tremelimumab, PE + anlotinib, and PE + benmelstobart + anlotinib. HRQoL data were insufficient for quantitative synthesis because measurement instruments and reporting formats differed across studies; therefore, we summarised the findings narratively. In people with extensive-stage SCLC, several ICI-based combinations with PE chemotherapy improve OS compared with PE alone (high-certainty evidence), although the magnitude of benefit varies across regimens. Some combinations probably or may have little to no effect on OS. Effects on PFS and ORR vary across treatments, and some combinations increase the risk of AEs whereas others result in little to no difference. HRQoL data were insufficient for quantitative synthesis, and so we are unable to draw conclusions about this outcome. The certainty of the evidence varies across outcomes and comparisons, reflecting differences in study design, variability in safety reporting, and limited direct head-to-head comparisons. Further RCTs directly comparing commonly used first-line regimens, with consistent reporting of AEs and patient-reported outcomes including HRQoL, are needed to reduce uncertainty and inform treatment decisions. Takeshi Hasegawa and Hisashi Noma were supported by the Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239). Protocol available via doi.org/10.1002/14651858.CD015738.
Since the onset of the 2023 Israel-Gaza war, the healthcare system in the Gaza Strip has nearly collapsed. More than 70,937 casualties and 171,192 injuries have been reported, yet limited data exist on injury types and outcomes. Critical care services are essential during conflicts. This study aimed to determine causes of intensive care unit (ICU) admissions, associated injuries, complications, and outcomes in the Gaza Strip. We conducted a prospective cohort study of all adult and pediatric patients admitted to the ICUs at European Gaza Hospital and Shuhada Al-Aqsa Hospital between May 29 and June 30, 2024. Outcomes of interest were causes of admission, survival, types of complications, and length of stay. A total of 115 patients were admitted. Median age was 27 years (interquartile range 18-38), including 30 pediatric patients (26%). Thirty-five patients were female (30%). Trauma with or without burns accounted for 75 admissions (65%), while 27 (23.5%) had medical causes. Among trauma patients, 56 (75%) were from explosive injuries; traumatic brain injury was most common (30/75, 40%), including 10 of 21 pediatric trauma patients (47.6%). During ICU stay, 12 patients developed sepsis (10.6%), 10 developed septic shock (8.8%), and 12 developed multiorgan dysfunction (10.6%). Of 112 patients with known disposition, 64 were discharged and 48 died (43%). Median ICU survival was 6 days (95% confidence interval 5-17), and 17 days for pediatric patients (95% confidence interval 5-not calculable). Severe traumatic brain injury (33%) was the leading cause of death, followed by septic shock (22%). The high burden of trauma, complications, and mortality reflects the critical collapse of Gaza's healthcare system. Women and children represented a substantial proportion of ICU patients, highlighting civilian vulnerability. Urgent international medical intervention, humanitarian support, and a permanent ceasefire are essential to prevent continued loss of life.
Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder that is associated with a broad range of symptoms, including constitutional, gastrointestinal, neuropsychiatric, dermatologic, respiratory, and hematologic or lymphoreticular problems. These broad symptoms can impact the daily lives of people living with iMCD, creating a high symptom burden. Despite this, no robust, disease-specific patient-reported outcome measure (PROM) for subjective iMCD symptom burden exists. This limits accurate symptom monitoring, impacts sensitive end point selection in clinical trials, and represents a regulatory gap in patient-centered evidence generation when evaluating iMCD treatments. This protocol describes the international multistakeholder Idiopathic Multicentric Castleman Disease Symptom Burden Scale (ISBUS) project. The primary aim of this project is to develop and preliminarily evaluate the measurement properties of a novel PROM for capturing symptom burden (ie, perceived symptom frequency and impact on daily life) in people living with iMCD. The central objective is to produce a valid and robust PROM that can be used to assess iMCD symptom burden in research, clinical trials, and symptom monitoring in clinical practice. The project has a mixed methods design, split into 4 sequential stages, with collaborative advisory input throughout. Stage 1 uses existing data and consultation with expert clinical and patient advisors to generate draft PROM content. Stage 2 uses qualitative cognitive debriefing interviews (n=10) to evaluate the content validity of the draft PROM content and enable meaningful revisions. Stage 3 involves a cross-sectional quantitative survey design in people living with iMCD (n≥50), allowing for psychometric analyses of structural validity (using classical test theory and/or Rasch methodology), construct validity (known-group validity and correlational methods), and internal consistency reliability (Cronbach α). Stage 4 uses a mixed methods design, including longitudinal quantitative survey evidence (n≥20) and qualitative interviews (n=10), triangulated to estimate preliminary meaningful change estimates for the new PROM. The project is international in scope, with primary data collection in 6 countries (ie, Australia, Brazil, Canada, New Zealand, the United Kingdom, and the United States). Funding for ISBUS began in June 2023 and is ongoing. As of March 2026, stage 3 had been completed, with 51 people living with iMCD completing the survey, and stage 4 was ongoing, with 32 follow-up surveys completed. Analyses for stages 1-3 were completed and are expected to be published in 2026, followed by stage 4 findings in 2027. The aim of the ISBUS project is to produce a novel symptom burden PROM codeveloped with patients with iMCD to measure what matters to patients with iMCD. It is anticipated that the new PROM will be used in iMCD research, as a secondary end point in trials, and as a clinical tool to monitor symptom burden in the management of iMCD. ClinicalTrials.gov NCT05995834; https://clinicaltrials.gov/study/NCT05995834. DERR1-10.2196/96022.
Family Presence During Resuscitation (FPDR) is a key component of family-centred care in paediatric settings, supported by international guidelines. However, limited evidence exists regarding how nurses' perceptions of FPDR relate to self-confidence during paediatric resuscitation. This study investigated the relationship between FPDR perceptions and self-confidence levels among paediatric nurses in critical care units. A descriptive, cross-sectional study was conducted between April 10 and June 20, 2025, with nurses working in paediatric critical care units of a tertiary city hospital. Data were collected through face-to-face survey administration using a Personal Information Form and the Family Presence Risk-Benefit Scale, and analysed using descriptive statistics, correlation analyses, and multiple linear regression. A total of 194 eligible nurses were approached, of whom 138 completed the survey, yielding a response rate of 71.1%. The majority of nurses opposed FPDR, citing concerns related to team communication, increased stress, interruption of medical interventions and risk of violence. Mean total self-confidence and risk perception scores were 47.24 ± 18.06 and 32.75 ± 10.37, respectively. Age, professional experience and certificate status did not significantly predict risk perception or self-confidence. Postgraduate education significantly increased risk perception, while working in paediatric haematology units significantly decreased self-confidence levels. A weak but statistically significant positive correlation was found between risk perception and self-confidence (rs = 0.25, 95% CI [0.09, 0.40], p = 0.013). The findings indicate that paediatric nurses' perceptions of family presence during resuscitation are influenced more by clinical and organisational context than by individual experience or certification. These results highlight the need for clear institutional policies and structured paediatric-specific training to support the safe implementation of family-centred resuscitation practices. The findings may inform the development of context-sensitive institutional policies and structured educational programs to support safer implementation of family-centred resuscitation practices.
The chances of oral squamous cell carcinoma (OSCC) being diagnosed at an early stage are very low, and this leads to a poor prognosis. The presence of circulating miRNAs (miRNAs) in blood or saliva is now a potential non-invasive diagnostic biomarker, although the diagnostic accuracy of the studies reported remains vastly different due to differences in biofluids, miRNA panels, disease spectrum, and platforms. We did a meta-analysis of diagnostic accuracy and a systematic review in accordance with PRISMA-DTA 2020 guidelines (PROSPERO: CRD420251274288). Articles that evaluated circulating miRNAs in any biofluid in diagnosing OSCC were taken into consideration. A Bayesian bivariate random-effects model was used to pool together the sensitivity, specificity, likelihood ratios, diagnostic odds ratios and the summary receiver operating characteristic (sROC) curves. Heterogeneity sources were analyzed using pre-constructed subgroup analysis and meta-regression. The number of studies that were evaluated in totality was seventeen and seven were incorporated in the meta-analysis. The pooled sensitivity of the circulating miRNAs towards the detection of OSCC was 0.89 (95% CI: 0.77-0.95) and the pooled specificity was 0.88 (95% CI: 0.75-0.95). It had a pooled positive likelihood ratio (PLR) of 7.25 (95% CI: 3.42-16.08), a negative likelihood ratio (NLR) of 0.13(95% CI: 0.05-0.27), and a diagnostic odds ratio (DOR) of 59.69(95%CI:14.33-209.95). Good performance in discriminating was also noted in the sROC curve with an area under the curve value of approximately 0.90. However, substantial between-study heterogeneity was observed (τ ≈ 0.93 for sensitivity; τ ≈ 0.83 for specificity), and the 95% credible intervals around the DOR were wide (14.33-209.95). Individual studies of multi-miRNA panels reported AUCs up to 0.98, though pooled subgroup estimates were limited by small study numbers and wide uncertainty. Circulating miRNAs and in particular multi-miRNA saliva-based profiles provide promising but heterogenous diagnostic accuracy for OSCC. While individual panel studies have reported high AUCs, the current pooled evidence-derived from only seven small, mostly case-control studies of advanced-stage disease-does not yet establish utility for true early detection or population screening.
Atherosclerotic peripheral arterial disease (PAD) can lead to chronic limb-threatening ischemia (CLTI) and limb loss. Treatments include lifestyle modifications, medications, and both open and minimally invasive operative approaches, including balloon angioplasty. Drug-eluting balloon (DEB) angioplasty is a promising alternative to uncoated balloon angioplasty for treating PAD. Ballooning and coating the inside of atherosclerotic vessels with cytotoxic agents inhibits cellular mechanisms responsible for atherosclerosis and neointimal hyperplasia, thereby preventing or postponing its complications. Although economic analyses may have demonstrated the cost-effectiveness of DEB angioplasty, they remain considerably more expensive than uncoated balloons, and there is uncertainty around their effectiveness. This is an update of our previously published 2016 review. To evaluate the benefits and harms of DEB angioplasty compared with uncoated, plain old balloon angioplasty (POBA) in people with symptomatic lower-limb PAD. We systematically searched the following databases for randomized controlled trials and controlled clinical trials: Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Ovid, and CINAHL EBSCO. We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov. We used the bibliographies of relevant papers to identify other studies. The most recent searches were carried out on 13 March 2023. We included randomized controlled trials comparing DEB angioplasty with POBA for intermittent claudication or critical limb ischemia (CLI). We used standard Cochrane methods. Our primary outcome was amputation. Our secondary outcomes included amputation-free survival, secondary vessel patency, change in ankle-brachial index (ABI), change in quality of life (QoL), change in functional walking ability, and all-cause mortality. We used GRADE to assess the certainty of evidence for selected outcomes (amputation, secondary vessel patency including target lesion revascularization and binary restenosis, change in ABI, and all-cause mortality). A total of 31 trials randomizing 5292 participants met the inclusion criteria. Nineteen trials included femoropopliteal arterial lesions, nine included tibial arterial lesions, and three included both. The trials were carried out in Europe, the US, China, Singapore, Jordan, Japan, and New Zealand. All trials used paclitaxel. All but four trials were industry-sponsored. There was heterogeneity in the frequency of stent deployment and antiplatelet regimens between trials. Participants were followed up for up to five years. There were better outcomes with DEB angioplasty for target lesion revascularization at one year, from 204 per 1000 lesions with POBA to 80 per 1000 lesions with DEB angioplasty (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.28 to 0.41; 23 studies, 4172 participants; P < 0.00001; low-certainty evidence). DEB angioplasty was also superior for binary restenosis at one year, from 443 per 1000 vessels with POBA to 187 per 1000 vessels with DEB angioplasty (OR 0.29, 95% CI 0.23 to 0.38; 8 studies, 1288 participants; P < 0.00001; moderate-certainty evidence). There was no difference between DEB angioplasty and POBA in amputation at one year, from 16 per 1000 participants with POBA to 22 per 1000 participants with DEB angioplasty (OR 1.45, 95% CI 0.91 to 2.29; 27 studies, 4469 participants; P = 0.12; moderate-certainty evidence); all-cause mortality, from 45 per 1000 participants with POBA to 44 per 1000 participants with DEB angioplasty (OR 0.97, 95% CI 0.71 to 1.32; 25 studies, 4312 participants; P = 0.83; moderate-certainty evidence); or change in ABI, from 0.1 to 0.35 higher with POBA and 0.03 higher to 0.03 lower with DEB angioplasty (mean difference (MD) 0, 95% CI -0.03 to 0.03; 5 studies, 1156 participants; P = 0.96; moderate-certainty evidence), although none of the studies were powered to detect a significant difference in these clinical endpoints. Meta-analysis of 31 trials with 5292 participants demonstrated that there may be evidence of an advantage of DEB angioplasty compared with POBA in several anatomic endpoints including late lumen loss, target lesion revascularization (low-certainty evidence), and binary restenosis (moderate-certainty evidence). Conversely, there may be little to no evidence of advantage with DEB angioplasty for clinical endpoints such as amputation (moderate-quality evidence), amputation-free survival, death (moderate-quality evidence), change in ABI (moderate-quality evidence), QoL, or functional walking ability. Well-designed randomized trials with long-term follow-up are needed to further compare DEB angioplasty with POBA adequately for both anatomic and clinical study endpoints.
Understanding how Ukrainian refugee children accessed the health care system after fleeing the war is essential to inform future preparedness and resource allocation in host countries. To use latent class analysis of registry data to identify distinct health care utilization profiles among young Ukrainian refugee children who accessed the health care system in southern Poland in 2022. This registry-based retrospective cohort study used electronic health record data from 2022 and included Ukrainian refugee children, aged 0 to 5 years, who received health care services in facilities in Małopolska Voivodeship, Poland. Participants were followed up from February 24 through December 31, 2022. The data were analyzed from April to October 2025. Healthcare utilization indicators among postwar displaced Ukrainian refugee children used as inputs to the latent profile analysis. Latent profile membership of health care utilization based on health care visit types, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coded diagnoses, and intensity of health care use, with temporal patterns of system entry and service trajectories examined after profile identification. The analytic sample included 9845 Ukrainian refugee children aged 0 to 5 years (4849 [49.3%] female) who received 35 199 health care services in Małopolska Voivodeship in 2022. Age at first health care contact was evenly distributed across categories (mean [SD] of 2.7 [1.6] years), 3802 children (38.6%) had a single recorded service, 1845 (18.7%) had more than 5 services, and nearly half (4505 [45.8%]) received care in the regional capital (Krakow). Based on latent class analysis, 5 pediatric patient profiles were identified: mostly primary care (5216 [53.0%]), hospitalized with infectious diseases (1539 [15.6%]), highest health care use (1329 [13.5%]), emergency care for injuries (900 [9.1%]), and dental and preventive care (861 [8.7%]), differing in visit type, diagnostic patterns, and health care utilization intensity. Temporal patterns varied across profiles with earlier system entry among children requiring hospitalization for infectious diseases or emergency care for injuries, and later entry among those using primary care or dental and preventive care. In this cohort study of pediatric Ukrainian refugees in southern Poland, distinct health care utilization patterns were observed with early reliance on hospital and emergency care followed by greater use of primary services. These findings underscore the need for refugee-hosting countries to rapidly adapt health care resources, prioritizing inpatient and emergency care in the initial months following a crisis.
As little is known about the disease burden of chronic hepatitis D virus (HDV) infection, this study examined health-related quality of life (HRQoL) and fatigue at different disease stages. This was a real-world quantitative cross-sectional survey of patients in Germany, Italy, Spain and the USA. Patients were recruited via their treating physicians. Patients who had received bulevirtide for hepatitis B or treatment licensed for HDV were excluded. Of 211 patients, 41% were noncirrhotic (F0-F3); 20% had liver cirrhosis with normal function (compensated); 20% had liver cirrhosis (F4) with impaired function (decompensated); 19% had hepatocellular carcinoma (HCC). Mean (standard deviation; SD) age was 54.5 (11.5) years, 75% were male. ANOVA showed a significant decrease (indicating poorer HRQoL) in EQ-5D-3L visual analogue scale (VAS) scores and index values with worsening disease stage and increasing severity (all p < 0.0001). All domain scores of the Hepatitis Quality of Life Questionnaire v2 (except positive wellbeing) worsened with progressing disease and increasing symptom severity (all p ≤ 0.0001). Mean Fatigue Severity Scale (FSS) total scores also increased, indicating greater fatigue, with worsening of disease and increasing symptom severity (both p < 0.0001). HDV infection significantly impacts patients' HRQoL and fatigue, particularly for patients at later disease stages. Treatments that slow disease progression, reducing the burden of HDV infection, are needed.
Emergence agitation is a clinically relevant phenomenon during recovery from general anesthesia. This study aimed to compare the effects of remimazolam and propofol as anesthetic induction agents on emergence agitation. This retrospective propensity score-matched study included adult patients undergoing elective transurethral endoscopic urologic surgery under general anesthesia. Patients were divided into remimazolam- or propofol-based induction groups. The primary outcome was the incidence of emergence agitation, defined as a Ricker Sedation-Agitation Scale (RSAS) score ≥ 5 during emergence. Secondary outcomes included the severity of emergence agitation, extubation time, postoperative pain scores, use of analgesics or antiemetics in the post-anesthesia care unit (PACU) and risk factor identification. A total of 239 patients were analyzed before matching, and 99 matched pairs were generated. After matching, the incidence of emergence agitation was significantly lower in the remimazolam group compared with the propofol group (13.1% vs. 36.4%; P = 0.001). Remimazolam-based induction was independently associated with a reduced risk of emergence agitation (odds ratio 0.23, 95% confidence interval 0.09-0.56; P < 0.001). The distribution of RSAS scores demonstrated reduced severity of agitation in the remimazolam group. Extubation time, postoperative pain scores, and PACU medication did not differ between groups. Younger age and male sex were identified as independent risk factors. Remimazolam-based anesthetic induction reduced incidence and severity of emergence agitation compared with propofol, without delaying extubation or impairing early postoperative recovery. Remimazolam may represent a favorable induction agent for adult patients at risk for emergence agitation.
Chronic limb threatening ischemia (CLTI) in older adults is associated with severe morbidity and high mortality. The rising prevalence is largely driven by the aging population and confronts healthcare systems with challenges like increasing demand for chronic care, staff shortage and rising healthcare costs. To improve post-operative outcomes and reduce the burden on healthcare systems, multimodal prehabilitation has gained interest and has the potential to improve post operative outcomes. However, evidence of the effect in older adults with CLTI remains scarce. The aim of this study is to determine whether a multimodal multicomponent prehabilitation program (MMPP) reduces length of stay and improves clinical, patient-reported and economic outcomes of older adults with CLTI. We developed a multicenter randomized controlled trial, with embedded cost-effectiveness analyses.. CLTI-patients aged 65 years or older, planned for revascularization, and their primary informal caregiver (IC) will be eligible. A total of 300 patients will be randomized to receive either standard preoperative care or a 2-week MMPP. All patients receive a general health screening. The MMPP includes physiotherapy and, if indicated, referral to a geriatrician, dietician or smoking-cessation coach, ferric carboxymaltose infusion or pre-arranged homecare. The primary outcome is length of stay. Exploratory secondary outcomes include minor complications, quality of life of patient and IC and health related quality of life. Descriptive secondary outcomes include 30-day and 6-month mortality, major complications, readmissions, burden on the IC, cost-effectiveness; and experiences and preferences regarding shared decision making. To the best of our knowledge, this is the first randomized controlled trial to evaluate the effect of an MMPP within older CLTI-patients. Findings will inform healthcare professionals whether an MMPP should be implemented in routine vascular surgical practice to reduce length of stay and improve clinical and patient-centered outcomes. The study is registered at the International Clinical Trials Registry Platform (NL-OMON58069).
Mpox remains an ongoing global health concern, driven by an ongoing clade I outbreak in Central Africa, which has caused substantial morbidity and mortality. Despite deployment of the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine, data on the durability of vaccine-induced immune responses remain limited, particularly in African populations, women and people with HIV, highlighting the need for context-specific immunogenicity data. Mpox-Vax AFRIVAC is a prospective, multicentre observational cohort study conducted in Uganda, Tanzania and the Democratic Republic of the Congo (DRC). Adults eligible for MVA-BN vaccination for mpox prevention or who received a first dose within 28 days prior to enrolment are followed for 48 weeks. Serial blood samples are collected to quantify binding antibody responses and assess their durability over time. The primary outcomes are mean geometric MVA-BN-specific antibody titres at week 48 and the rate of antibody decay from week 6 to week 48. Secondary outcomes include antibody kinetics at intermediate time points, factors associated with immune responses, breakthrough infection and vaccine safety. Analyses will use descriptive and longitudinal statistical methods to evaluate immune response trajectories and associated host factors, including HIV status, age and sex. The study is conducted in accordance with the Declaration of Helsinki, registered at the Pan African Clinical Trials Registry (PACTR202601855406764) and publications will be in accordance with the recommendations of the International Committee of Medical Journal Editors. The study has received ethical approvals in Uganda, DRC and Tanzania. Approval for Uganda has been obtained from Uganda Virus Research Institute Research and Ethics Committee (GC/127/1062) and Uganda National Council for Science and Technology (HS5575ES), for DRC from the Institutional Committee of Health ethics (UCB/CIES/PB/001/2025) and for Tanzania from the National Institute for Medical Research (NIMR/HQ/R.8a/Vol.IX/5187). PACTR202601855406764.
Transcatheter mitral valve replacement (TMVR) is an alternative for patients with mitral regurgitation (MR), but data on transfemoral (TF) devices are limited. The aim of this study was to evaluate clinical, echocardiographic, and functional outcomes following TF TMVR in an international registry. The CHOICE-MI (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) Registry included patients undergoing TMVR with dedicated devices at 41 international centers. This analysis included only TF TMVR. Outcomes were assessed per Mitral Valve Academic Research Consortium criteria. Echocardiographic, functional, and clinical outcomes up to 2 years were reported. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization at 2 years. Predictors were identified using multivariable Cox regression. A total of 124 patients (median age 79 years [Q1-Q3: 75-83 years], 50% women, median European System for Cardiac Operative Risk Evaluation II score 5.0% [Q1-Q3: 3.3-8.5]) underwent TF TMVR with 9 different devices. The leading MR etiology was primary MR (n = 49 [39.5%]), with mitral annular calcification in 12.9%. Technical success was achieved in 113 of 124 patients (91.1%), and procedural mortality was low (1 of 124 [0.8%]). Residual MR ≤1+ was achieved in 94.9% at discharge, with stable results at follow-up. The rates of cardiovascular mortality were 14.7% (95% CI: 7.9%-21.5%) and 20.3% (95% CI: 11.4%-29.1%) and of the primary endpoint 44.1% (95% CI: 30.6%-50.0%) and 52.4% (95% CI: 40.2%-62.1%) at 1 and 2 years, respectively, and NYHA functional class had significantly improved at 1- and 2-year follow-up. Atrial fibrillation was an independent predictor of the primary endpoint, whereas technical success was associated with survival. TMVR using dedicated TF devices demonstrates favorable safety, durable MR reduction, and sustained functional improvement in high-risk patients. (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency Registry [CHOICE-MI Registry]; NCT04688190).
Provincial mortality profiles are essential for local prevention and health-service planning. However, they are reported less frequently than national summaries in Iran. We described cause-of-death patterns and temporal changes in Fars Province from 2015 to 2024, including the disruption during the coronavirus disease 2019 pandemic. We analyzed death registration records from the Fars provincial civil registration system, including age, sex, residence status, place of death, and an underlying cause coded using the International Classification of Diseases (ICD), 10th revision, and mapped to major cause groups. We summarized distributions by key strata and assessed temporal patterns using annual counts and within-registry proportions. Trend tests and multivariable logistic regression evaluated associations of calendar year and pandemic period with major cause groups, while unsupervised clustering summarized mortality profiles among non-neonatal records. After cleaning, 199,107 records were included. Diseases of the circulatory system accounted for 45.4% of deaths, followed by respiratory diseases, neoplasms, and external causes. All-cause deaths rose sharply in 2020-2021, with concurrent increases in respiratory and infectious causes. Cause composition varied by residence status and place of death, and clustering distinguished younger external-cause deaths from older disease-dominant profiles. Mortality in Fars Province during 2015-2024 was dominated by circulatory diseases, with heterogeneity by demographic and contextual factors and a major pandemic-era increase in deaths. The findings supported prioritizing cardiovascular risk reduction and timely acute care, targeted injury prevention for younger groups, strengthened rural access to prevention and emergency services, and preparedness for future infectious surges.
Tumor-induced osteomalacia (TIO) is an ultra-rare, paraneoplastic syndrome caused by tumors secreting fibroblast growth factor 23 (FGF23). In children, TIO may be mistaken for more common causes of rickets and osteomalacia, including monogenic forms, leading to long diagnostic delays. This review aimed to identify evidence on the diagnostic journey and burden of TIO in pediatric patients. A literature review was conducted to identify publications reporting disease characteristics, investigations, treatments, and clinical outcomes in pediatric patients diagnosed with TIO. In total, 41 studies were included in the review, reporting on 46 pediatric patients. Mean age at presentation was 11.2 years (standard deviation [SD]: 4.6). The majority of individuals (60.9%) were male. The most commonly reported symptoms at presentation were pain (65.2%), weakness (47.8%), and impaired physical function (43.5%). Rickets was reported in 45.7% of patients and fractures in 34.8% of patients. Mean time from onset of symptoms to diagnosis was 4.3 years (SD: 2.6) and mean number of imaging procedures per patient was 5.4 (SD: 2.7). Low serum phosphate concentration for age was reported in 93.5% of patients at presentation. Attempted surgical resection was reported in the majority of patients (89.1%) and was successful in 60.9%. Pediatric-onset TIO is associated with a substantial symptomatic and healthcare burden. Increasing awareness of TIO in children may prevent delays in diagnosis, reduce the need for radiation-conferring tests, and lower morbidity due to effective management. Further research in this area is needed to address the scarcity of data available in pediatric patients.
Rare diseases affect a small percentage of the population but collectively impact millions worldwide. In the Middle East, the challenges are intensified by regional factors such as high rates of consanguinity, sociocultural stigma, limited diagnostic capacity, and inadequate healthcare infrastructure. These challenges often lead to delayed diagnoses, restricted access to treatment, and poor quality of life for affected individuals and their families. The Rare Advocacy Council conducted two 1.5-hour virtual expert panels involving 14 regional and international stakeholders (5 clinicians, 4 patient advocates, and 5 international academic experts) to identify and prioritize the challenges of managing rare diseases in the Middle East region. Discussions were organized across four domains: disease recognition and diagnosis, the patient journey and continuum of care, access to timely diagnostics, and access to adequate treatment, followed by structured online voting (involving only clinicians and patient advocates; n = 9), discussions focused on prioritization, and a descriptive follow-up survey to identify the most critical barriers and propose actionable solutions. Key challenges identified included the lack of national disease registries, limited public awareness, underrepresentation of patient voices in decision-making, fragmented multidisciplinary care, and restricted access to diagnostics and advanced therapies. Top priorities included developing national registries, enhancing media-driven education, strengthening collaboration among care providers, and improving treatment accessibility through policy reforms. Effective management of rare diseases in the Middle East requires a coordinated, patient-centered approach. Strengthening health system infrastructure, investing in education, and aligning policy with patient needs are essential for sustainable improvement. Collaborative action among policymakers, healthcare providers, and advocacy groups can significantly advance care delivery and improve outcomes for individuals living with rare diseases.
The interactions of pulmonary and renal physiology that underlie acute lung injury (ALI) and acute kidney injury (AKI) have been recognized for nearly a century. The understanding of lung-kidney crosstalk has evolved and is recognized as an important factor in patient management and outcomes. We aim to describe the association between fluid accumulation (FA) and ALI with outcomes of critically ill children and young adults requiring continuous renal replacement therapy (CRRT). Planned secondary analysis using data from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). ALI severity was defined using the Berlin oxygenation criteria. Fluid accumulation was categorized as ≤ 10%, > 10-20%, and > 20% at CRRT initiation. Illness severity was quantified using the Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2). The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included (1) 28-day mechanical ventilation (IMV) free days, (2) 28-day ICU free days, and (3) major adverse kidney events at 90 days (MAKE90) defined by death, persistent kidney dysfunction (eGFR reduction by 25% of baseline), or new dialysis requirement. This is a multinational retrospective cohort study. Invasively ventilated patients aged 0-25 years from January 2015 to December 2021 requiring CRRT for AKI or FA with ALI. There were no interventions. A total of 312 patients were included in the analysis. ALI was mild in 67 (21.5%), moderate in 142 (45.5%), and severe in 103 (33.0%). Fluid accumulation was ≤ 10% in 166 (53.2%), > 10-20% in 60 (19.2%), and > 20% in 86 (27.6%). The ICU mortality was 44.6% (139/312). In the multivariable analysis, neither ALI nor FA category was associated with mortality or MAKE90. Time to CRRT initiation (aOR 1.04, 95% CI 1.01-1.08) and illness severity (aOR 1.25, 95% CI 1.14-1.37) were associated with mortality.  In children and young adults with ALI receiving CRRT for AKI or FA, longer time to CRRT initiation and illness severity at CRRT initiation were associated with mortality. When accounting for multiple factors, neither ALI nor FA at CRRT initiation were associated with MAKE90 or mortality. Our findings warrant further exploration in a prospective cohort. • Acute kidney injury (AKI) and acute lung injury (ALI) commonly coexist in critically ill children and are associated with increased morbidity and mortality through bidirectional organ crosstalk. • Fluid accumulation (FA) worsens both AKI and ALI, with higher degrees of FA associated with worse outcomes, with continuous renal replacement therapy (CRRT) frequently used to manage the consequences of AKI and FA. • In this multicenter international cohort of children and young adults with ALI receiving CRRT, longer time to CRRT initiation and illness severity at CRRT initiation, but neither ALI nor FA at CRRT initiation were associated with mortality were associated with mortality. • These findings suggest that FA thresholds at the start of interventions may be less discriminatory in populations with dynamic processes such as severe multiple organ failure.