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Failure modes and effects analysis for clinical implementation of online adaptive radiotherapy: A systematic review.

BACKGROUND: The accuracy of radiotherapy is limited by anatomical variations occurring over time scales ranging from sub-seconds to days. Online Adaptive Radiotherapy (OART) addresses this by enabling daily plan adaptation based on real-time imaging. While OART offers improved dose conformity, its dynamic, time-constrained workflow introduces novel failure modes that challenge traditional quality assurance protocols. PURPOSE: This study aims to synthesize the existing literature on Failure Modes and Effects Analysis (FMEA) for OART to systematically catalog risks and identify mitigation strategies. METHODS: A systematic literature search was conducted to identify studies applying FMEA to OART workflows. Eleven studies were included, covering MR-guided (ViewRay MRIdian, Elekta Unity), CBCT-guided (Varian Ethos), and MR-enhanced C-arm linac systems. To address heterogeneity in risk scoring methodologies (e.g., TG-100 10-point scales vs. 5-point rankings), extracted failure modes were harmonized into a standardized three-tier risk classification system (Class I: Low, Class II: Intermediate, Class III: High). RESULTS: A total of 300 unique failure modes were identified, with 49.6 percent classified as high-risk (Class III). Analysis revealed that the majority of high-risk failures were concentrated in the online treatment delivery phase, specifically within human-computer interactions and anatomical contouring steps. CONCLUSIONS: This study supports the development of tailored, robust QA frameworks that prioritize human factors and process consistency to guide safe implementation in diverse clinical settings.

Humans

Alginate-based edible coating incorporating green tea extract for preserving postharvest quality and safety of white mushrooms (Agaricus bisporus).

This study aimed to evaluate the effects of a sodium alginate based edible coating incorporated with green tea extract (GTE) (Camellia sinensis) on the postharvest quality attributes and antimicrobial activity against Listeria monocytogenes in white mushrooms during refrigerated storage. The phenolic profile of GTE was characterized, and its minimum inhibitory concentration (MIC) against L. monocytogenes (1.6&#xa0;mg/mL) was determined. Sodium alginate coatings, with (ALG-GTE) or without GTE (ALG) at MIC (1.6&#xa0;mg/mL), were characterized (functional groups, solubility in water, moisture, thickness, water contact angle and color) for their chemical and physical properties. The effects of ALG-GTE coatings on quality parameters (firmness, weight loss, color, pH, sugars and organic acids), enzymatic activity [polyphenol oxidase (PPO), peroxidase (POD) and pectin methylesterase (PME)], antimicrobial activity against L. monocytogenes (5 log CFU/g), and surface characteristics (3D optical profilometry) were assessed in white mushrooms (Agaricus bisporus) during refrigerated storage (8&#xa0;days, 4&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C, 90-95% RH). The ALG-GTE coatings preserved sugar composition, particularly rhamnose, reduced organic acids accumulation and delayed weight and firmness loss, reduced color changes, and decreased PME activity in coated white mushrooms. L. monocytogenes counts decreased by 1.4 log CFU/g after 1&#xa0;day, and no viable cells were detected after 2&#xa0;days (< 1.5 log CFU/g) in ALG-GTE coated white mushrooms. In addition, ALG-GTE coated white mushrooms exhibited smoother surfaces than uncoated samples. These findings highlight the potential of ALG-GTE coatings as a sustainable alternative capable of improving the microbiological safety and delaying the postharvest changes in fresh mushrooms.

Agaricus

Application of Perioperative Real-Time Fluorescence Imaging to Achieve High-Quality Debridement: A Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness of real-time fluorescence imaging (RTFI)-assisted debridement in managing chronic wounds compared with standard surgical debridement. APPROACH: This study was a patient-blinded, randomized clinical trial conducted from February 17, 2021, to July 30, 2021, on patients with chronic wounds. Patients were randomized to an RTFI group (M group) or conventional group (C group). The primary outcomes were as follows: percentage of residual bacterial area (preoperative and postoperative), number of debridements, high-quality debridement ratio, operation duration, and wound healing duration. RESULTS: A total of 100 patients were enrolled in both groups. No significant difference in the percentage of preoperative residual bacterial area or high-quality debridement ratio was seen. The M group underwent debridement an average of 2.6 times and had a significantly longer duration of operation (33.5 &#xb1; 12.7 min) than the C group (29.9 &#xb1; 10.4 min; p = 0.031). The postoperative residual bacterial area was significantly lower in the M than in the C group (6.83% &#xb1; 1.39% vs. 30.0% &#xb1; 12.37%, respectively; p < 0.001). The M group required significantly fewer wound healing days (49.2 &#xb1; 25.3 vs. 63.0 &#xb1; 27.9, p < 0.001). Secondary outcomes also demonstrated statistically significant differences in total hospitalized days (17.5 &#xb1; 9.3 vs. 21.5 &#xb1; 12.5, p < 0.01), days of antibiotic use (15.5 &#xb1; 8.7 vs. 18.7 &#xb1; 6.7, p < 0.01), and reinfection rates (4 of 100 vs. 22 of 100, p < 0.001). INNOVATION: RTFI can detect signals from normal skin components and bacterial metabolites. Therefore, interpretation of RTFI results should be correlated with the clinical condition. RTFI is associated with high-quality debridement. This technique can also be applied in targeted biopsy and in training young staff to mature debridement procedures. CONCLUSION: RTFI in debridement is associated with favorable clinical outcomes and may have a positive influence on chronic wound healing.

Humans

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals

Continuous Ultrasound-guided Erector Spinae Plane Block Versus Thoracic Paravertebral Block for Postoperative Analgesia in Patients Undergoing Thoracotomy.

OBJECTIVES: To compare postoperative analgesia using continuous ultrasound-guided erector spinae plane block (ESPB) versus thoracic paravertebral block (TPVB), with dynamic visual analog scale (VAS) during coughing as the primary outcome. Secondary outcomes included static VAS (at rest), hemodynamic changes, side effects, total opioid consumption, time of first rescue analgesia, length of hospitalization, anesthesia recovery time, postanesthesia care unit stay, time to first ambulation, and patient satisfaction. METHODS: The study included 40 cases scheduled for elective thoracotomy admitted to the cardiothoracic surgery unit of Menoufia University Hospital. Patients were equally randomized into 2 groups, 20 patients each receiving either ultrasound-guided ESPB or TPVB (control group). Both groups received 20&#xa0;mL of 0.25% bupivacaine as a loading dose followed by continuous infusion of 0.125% bupivacaine at 5&#xa0;mL/h, with patient-controlled boluses of 20&#xa0;mL on demand. RESULTS: Dynamic visual analogue pain scale scores were significantly lower in the ESPB group at 6, 9, 12, and 24 hours ( P =0.008, 0.035, 0.001, 0.006). Morphine consumption was significantly reduced in the ESPB group ( P < 0.001). Hypotension was more frequent in TPVB (40% vs. 10%, P =0.028). No significant differences were observed in hospital stay or patient satisfaction. DISCUSSION: The utilization of continuous ultrasound-guided ESPB demonstrated better postoperative visual analogue pain scale scores and a significant decrease in opioid consumption, with fewer side effects than TPVB.

Humans

Integrated multi-omics profiling of amniotic fluid identifies predictive biomarkers for fetal growth restriction trajectories.

BACKGROUND: Fetal growth restriction (FGR) is a complex condition with highly heterogeneous clinical outcomes, making prenatal distinction between transient and persistent growth failure challenging. This study aims to identify amniotic fluid (AF) biomarkers capable of differentiating distinct FGR trajectories and characterizing persistent growth failure mechanisms. METHODS: Integrated proteomic and metabolomic profiling was performed on AF samples from transient FGR (n&#x2009;=&#x2009;11), persistent FGR (n&#x2009;=&#x2009;9), and healthy controls (n&#x2009;=&#x2009;13). Diagnostic and prognostic models were developed using multivariate analysis. Selected protein candidates were validated via ELISA in an independent cohort (n&#x2009;=&#x2009;69). RESULTS: Multi-omics analysis revealed distinct molecular signatures for FGR stratification. A two-protein diagnostic panel (PDGFA and phospho-STAT5A) achieved an AUC of 1.000 in the discovery stage and 0.780 in the external validation cohort. For prognostic assessment, a molecular signature including IREB2, HLA-C, and PLXNB2 accurately predicted persistent growth failure from transient recovery (AUC = 0.966). Cross-platform integration highlighted the mass spectrometry-derived WASHC2C as a central hub protein with a significant progressive increase across the control, transient, and persistent groups (p&#x2009;<&#x2009;0.001). CONCLUSIONS: This study establishes a multi-omics framework for prenatal FGR stratification. Our findings identify distinct molecular&#xa0;signatures reflecting&#xa0;the intrauterine environment and provide high-performance molecular tools for predicting divergent fetal growth trajectories to guide personalized clinical decision-making.

Humans

Smartphone Apps for Preventing Adolescent Health Problems Among Health Care Professionals: Systematic Search and Quality Assessment.

BACKGROUND: Health care professionals must consider multiple dimensions of prevention when consulting with adolescents. Identifying risky behaviors early in adolescence is crucial for reducing both morbidity and mortality. General practitioners are increasingly eager to incorporate digital tools for prevention into their consultations with adolescents; however, the relevance and clinical validity of these digital tools are not always established or well-known. Consequently, primary care professionals require guidance and support in selecting relevant mobile health (mHealth) tools. OBJECTIVE: The aim of this study is to identify relevant and useful digital apps to help primary care professionals detect at-risk adolescents across all recommended areas of prevention: orthopedics, mental health, substance abuse, risk behaviors, sexual health, vaccinations, social relationships, and nutrition. METHODS: A systematic review of smartphone apps, with an analysis of content quality, was carried out by 4 researchers using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. The App Store and Google Play Store platforms were surveyed. The inclusion criteria were as follows: free of charge, date of last update, availability in French or English, relevance of the preventive approach to adolescents, and scientific validation. Four health care professionals assessed the apps: 2 selected the apps relevant to health care professionals, then 3 analyzed these apps using the French version of the Mobile App Rating Scale (MARS-F). Intraclass correlation coefficient, model (2,1) (2-way random effects, absolute agreement, single measures); standard error of measurement; and mean absolute error were also calculated. RESULTS: A total of 976 apps were identified, 49 of which had disappeared from the platforms prior to analysis. Nine apps were retained. Seven (0.72%) were included after evaluation using the MARS-F: 2 on mental health and 5 on sexual health (including 3 on contraception only). The mean MARS-F interrater score ranged from 2.5/5 to 3.8/5. The global MARS-F score demonstrated a pooled SD of 0.60 and an intraclass correlation coefficient (2,1) of 0.0003, resulting in a calculated standard error of measurement of 0.60. The average discrepancy between raters was a mean absolute error of 0.53. CONCLUSIONS: No similar studies have been identified in the literature that specifically focus on mobile apps designed to support health care professionals in delivering preventive care to adolescents. Of the 8 areas of prevention identified as relevant for adolescents, only 3 are addressed by the apps validated through our methodology (5 focus on sexual health). Consequently, current apps are insufficient to support health care professionals in their overall preventive work with adolescents. Such a review should be conducted systematically prior to the development of any new tool to prevent duplication and channel creative efforts toward truly innovative digital solutions. Furthermore, a thorough analysis of relevant, recommended websites is essential, as these resources complement the use of mobile apps designed for health care professionals.

Humans

Natural deep eutectic solvent in situ formation-based extraction method coupled to high-performance anion-exchange chromatography with pulsed amperometric detection for multiclass carbohydrates in hot pot bases.

A novel method was developed for the simultaneous extraction of fourteen multiclass carbohydrates from high-fat foods via the in situ formation of deep eutectic adducts from analytes and acetate ions. Different natural deep eutectic solvents (NADESs) composed of fructose and organic acids were tested as extraction solvents. A model NADES formulated with sodium acetate and fructose was characterized using Fourier transform infrared (FTIR) spectroscopy and hydrogen nuclear magnetic resonance (1H-NMR) spectroscopy. The critical extraction parameters were systematically optimized using multi-response surface methodology (MRSM) with a central composite design (CCD). The extract was analyzed using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) using a sodium hydroxide-sodium acetate eluent, which did not require organic solvents. This approach exhibited good linearity over the concentration range of 0.02-10 mg L-1, with correlation coefficients (r) ranging from 0.9994 to 0.9999. The limits of detection and quantification were in the ranges of 0.06-0.42 mg kg-1 and 0.19-1.3 mg kg-1, respectively, which were significantly lower than those of liquid chromatography (LC). The protocol was successfully applied to the determination of fourteen carbohydrates in forty-five hotpot seasoning samples. The recoveries ranged from 86.3% to 104.1%, with relative standard deviations (RSDs) of 0.9-7.1%. By integrating multiple techniques, this strategy simplifies operations, shortens extraction time, and achieves baseline separation of three carbohydrate classes that exhibit poor resolution using a conventional LC method. This study describes an efficient procedure for the simultaneous determination of multiple trace-level carbohydrates in complex samples using HPAEC-PAD.

Journal Article

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50&#xa0;&#x3bc;M, and intracellular concentrations and cell viability were monitored over 48&#xa0;h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry

Current Diagnostic Pathways for Rheumatoid Arthritis-Associated Interstitial Lung Disease Result in Substantial Underdiagnosis and Excess Mortality: A Multicenter Norwegian Quality Assurance Audit.

OBJECTIVE: Recent guidelines suggest risk-stratified screening for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the diagnostic gap between current routine care and this screening approach remains unquantified. We assessed currently detected RA-ILD in Norway, benchmarking findings against recent screening-based estimates of the true disease burden. METHODS: This 10-year quality assurance audit across six centers covered 43% of the Norwegian population. RA-ILD cases identified via ICD-10 codes were confirmed by manual chart review. Prevalence was calculated relative to a registry-derived total RA background population and benchmarked against a 10% expected target derived from recent prospective studies. Mortality was compared to a 3:1 frequency-matched RA control group using Cox proportional hazards regression. RESULTS: Among 17,305 RA patients, 188 (1.1%) had verified ILD; when benchmarked against an expected 10% prevalence, this indicates an 89% diagnostic gap in routine clinical care. Mean age at ILD detection was 67.5 years. Most cases (93.6%) possessed &#x2265;2 established risk factors for RA-ILD: 93.6% were seropositive, 76.1% had smoking histories, while RA onset age &#x2265;60 and persistently increased inflammatory laboratory markers were present in over half of patients. RA-ILD was associated with significantly increased mortality; 66 (4.1/100 person-years) deaths occurred in the RA-ILD group vs. 120 (2.3/100 person-years) among RA controls (HR 1.77; 95% CI: 1.31-2.39, p<0.001). CONCLUSION: When comparing to prevalence expectations, current routine care may leave a substantial proportion of cases undetected, primarily capturing a high-risk phenotype with excess mortality. Systematic, risk-stratified screening is needed to bridge this diagnostic gap, aiming to enable earlier intervention.

Interstitial lung disease

Comparison of Iodinated Contrast Doses Based on Total Body Weight and Lean Body Weight in Pediatric Patients: Impact on Image Quality and Contrast Exposure.

INTRODUCTION: Iodinated contrast dosing in pediatric computed tomography (CT) traditionally relies on total body weight (TBW), which may result in excessive contrast administration, particularly in patients with higher adiposity. Lean body weight (LBW)-based protocols have shown promise in adults but remain underexplored in children. Therefore, the aim of this study was to compare contrast volume requirements and hepatic enhancement quality among three dosing protocols: LBW-based, TBW-based, and the Control Group (CG), based on the institutional standard for pediatric abdominal CT. METHODS: This prospective study enrolled 66 patients (age 0-16 years) undergoing contrast-enhanced abdominal CT between September 2023 and August 2024. Patients were randomly assigned to receive iodinated contrast (iobitridol 350mg I/mL) dosed by: (1) LBW (0.63 g iodine/kg x LBW, calculated using Peters formula; n = 23), (2) TBW (0.46 g iodine/kg x TBW; n = 20), or (3) institutional control protocol (2 mL/kg x TBW, equivalent to 0.7 g iodine/kg; n = 23). Kruskal-Wallis, ANOVA, Two-way ANOVA, ANCOVA, Scheirer-Ray-Hare, and Cohen's Kappa tests with Likert scale were used. RESULTS: The LBW group received lower median contrast volumes (27 mL; IQR, 10-80 mL) compared to the TBW group (34.5 mL; IQR, 18-78 mL) and the CG group (40 mL; IQR, 13-80 mL), although the differences did not reach statistical significance (P > 0.05). Notably, this reduction did not compromise hepatic enhancement, which remained comparable to the CG (552 &#xb1; 139 HU; P = 0.107). CONCLUSION: Lean body weight may be a useful parameter for estimating contrast dose in pediatric abdominal CT, potentially reducing administered volumes without compromising diagnostic image quality. IMPLICATIONS FOR PRACTICE: These results provide early evidence that LBW-based dosing may support more individualized contrast administration in pediatric CT, potentially reducing exposure-related risks.

Humans

Congenital Laryngomalacia: Pathophysiology, Clinical Spectrum, and Holistic Management.

Congenital laryngomalacia is the most common cause of infant stridor and arises from interacting structural, neuromuscular, and inflammatory mechanisms that produce dynamic supraglottic collapse. Disease severity spans mild stridor to significant obstruction, aspiration, and failure to thrive, often influenced by comorbid medical conditions. Diagnosis relies on flexible laryngoscopy supported by instrumental swallowing studies and microdirect laryngoscopy and bronchoscopy when indicated. Most infants respond to conservative management, particularly targeted feeding modifications, while acid suppression offers benefit in selective cases. Supraglottoplasty provides effective, durable improvement for severe disease and significantly enhances infant outcomes and family quality of life.

Humans

Total ankle replacement versus nonoperative management for end-stage ankle osteoarthritis: A comparative analysis.

BACKGROUND: The optimal management of end-stage ankle osteoarthritis remains debated. This study compared short-term outcomes between non-operative treatment, total ankle replacement (TAR), and cases in which indicated surgery was delayed. METHODS: In this secondary analysis of prospectively collected data, treatment survival, Foot and Ankle Outcome Score (FAOS), and patient satisfaction were assessed at baseline and at 1- and 2-year follow-up. RESULTS: In a total of 316 patients one-year treatment survival was highest for TAR (99.3%), followed by NOM (94.4%) and delayed surgery (80.9%). TAR demonstrated significantly superior FAOS pain and quality-of-life scores compared with NOM and delayed surgery. Delayed surgery was associated with significantly worse pain and quality-of-life outcomes. Patient satisfaction was highest in the TAR group and lowest in the delayed surgery group. CONCLUSIONS: TAR provides superior pain relief, quality of life, and satisfaction compared with non-operative management in end-stage ankle OA. While NOM remains a valid option for selected patients, delaying indicated surgery results in inferior outcomes, underscoring the importance of timely, shared decision-making.

Humans

Improved quality of life and prolonged survival with add-on homeopathic treatment in patients with non-small cell lung cancer: a prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study.

BACKGROUND: Alongside conventional anticancer treatment, add-on homeopathy might help to alleviate adverse effects of conventional therapy. AIM: The aim of this study was to replicate previous studies on the effect of adjunctive homeopathy on quality of life (QoL) and survival in non-small cell lung cancer (NSCLC) patients. METHOD: In this prospective, randomized, placebo-controlled, double-blind, three-arm multicenter phase III study with quadruple-checked data analysis, we investigated the potential effects of an add-on homeopathic treatment compared to placebo in patients with stage IV NSCLC in terms of QoL. Ninety-eight received either individualized homeopathic medicinal products (HMPs; n&#x2009;=&#x2009;51) or placebo (n&#x2009;=&#x2009;47) in a double-blinded fashion. Fifty-two control patients without homeopathic treatment were only observed in terms of their survival rate. The ingredients of the various HMPs were mainly prepared of plant, mineral, or animal origin. The data entry and statistical analysis were subject to an exceptional quadruple-checked data analysis process. The analysis presented in this article was inspired by our earlier report of this trial published in The Oncologist in 2020, which was retracted by that journal in November 2025 after two corrections; a majority of the co-authors disagreed with this decision. The present article is based on the same trial dataset but was deliberately designed to highlight the unique research methodology: design and preparation by a lead statistician, data entry, data clearing and independent statistical evaluation were performed in four mutually independent steps, reporting follows the CONSORT statement, and the interpretation of the findings has been reframed conservatively. RESULTS: Global health status (QoL) was higher in the homeopathy group than in the placebo group after 9&#xa0;weeks and after 18&#xa0;weeks (p&#x2009;<&#x2009;0.001). With the exception of cognitive functioning at 9&#xa0;weeks and of pain, diarrhea and financial difficulties at 9&#xa0;weeks, all functional and symptom scales of the EORTC QLQ-C30 favored the homeopathy group (p&#x2009;<&#x2009;0.001 for the multivariate comparisons), with between-group differences exceeding the threshold of 10 points that is generally regarded as clinically meaningful. Median survival time over the 730-day observation period was 435&#xa0;days in the homeopathy group, 257&#xa0;days in the placebo group (p&#x2009;=&#x2009;0.010), and 228&#xa0;days in the non-randomized control group (p&#x2009;<&#x2009;0.001); the corresponding 2-year survival rates were 45.1%, 23.4%, and 13.5% (homeopathy vs. placebo p&#x2009;=&#x2009;0.020; homeopathy vs. control p&#x2009;<&#x2009;0.001). The difference between the placebo group and the non-randomized control group was not statistically significant (p&#x2009;=&#x2009;0.154). CONCLUSION: In this trial, add-on homeopathy was associated with better quality of life across most functional and symptom domains, with clinically meaningful effect sizes congruently to a previous open study. Survival time was significantly longer in the homeopathy group compared to both the placebo and control groups. Independent replication, ideally within contemporary immuno-oncological treatment regimens is required. TRIALS REGISTRATION: ClinicalTrials.gov; No.: NCT01509612; January 7, 2012.

Humans

Patient-reported outcome measures within European cohorts of severely injured patients: a systematic review and meta-analysis.

PURPOSE: Severe injury affects multiple health-related domains, yet comprehensive European data on patient-reported outcomes remain limited. This systematic review and meta-analysis evaluates patient-reported outcome measures (PROMs) use and outcomes in severely injured European cohorts. METHODS: A systematic search of four databases up to October 14, 2025, identified European studies from 2000 onward reporting PROMs in severely injured patients. Severe injury was defined as an Injury Severity Score&#x2009;&#x2265;&#x2009;16, Glasgow Coma Scale&#x2009;&#x2264;&#x2009;8, intensive care unit admission, spinal cord injury, traumatic amputations, or pelvic fractures. Two reviewers independently screened records, with disagreements resolved by a third reviewer. Meta-analysis was performed when &#x2265;&#x2009;3 studies reported comparable PROMs at similar follow-up timepoints. RESULTS: Of 2,479 studies, 119 were included. Most cohorts originated from the Netherlands (26%), Norway (18%), and Germany (16%). General severely injured cohorts were most frequently studied (61%), followed by traumatic brain injury (17%), and spinal cord injury (15%). In total, 94 PROMs were used across 277 follow-up timepoints. Health-related quality of life was assessed most frequently (63%), after that anxiety/depression (14%), post-traumatic stress (9%), and social functioning (6%). At one year follow-up, the pooled EuroQol-5D-3&#xa0;L index score was 0.70 (95% CI 0.62-0.77) and VAS score was 68 (95% CI 60-75), indicating persistent impairment compared to population norms. CONCLUSION: Severely injured patients show persistent impairments with incomplete restoration of pre-injury functioning. Despite increased PROMs use, heterogeneity in selection and outcome reporting limits comparability, underscoring the need for standardised PROM assessment to improve outcome evaluation after severe injury.

Humans

The Impact of Nurse-to-Patient Ratios on Nurses' Burnout, Job Dissatisfaction, and Intention-to-Leave: A Systematic Review and Meta-Analysis.

BACKGROUND: Adequate nurse staffing is essential for ensuring workforce well-being and patient safety. Imbalanced nurse-to-patient ratios contribute to burnout, job dissatisfaction, and turnover, which compromise care quality. OBJECTIVE: This systematic review and meta-analysis evaluated the impact of nurse-to-patient ratios on nurse burnout, job dissatisfaction, intention-to-leave, and patient outcomes. METHODS: A systematic search of PubMed, Scopus, and Web of Science identified cross-sectional studies examining nurse-to-patient ratios and related outcomes. RESULTS: Eighteen studies involving 183&#x2005;876 nurses from 4085 hospitals were included. Higher nurse-to-patient ratios increased the odds of burnout (OR: 1.08), job dissatisfaction (OR: 1.10), and intention-to-leave (OR: 1.09). Each additional patient per nurse increased mortality and readmission risks by 7% to 8%, with decreased perceived care quality. CONCLUSION: Higher nurse-to-patient ratios adversely affect nurses and patients. Ensuring adequate staffing is critical to prevent burnout and maintain safe, high-quality care.

Humans

Longitudinal Neurocognitive Changes for Patients With Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review With Structured Narrative Synthesis.

OBJECTIVES: Neurocognitive changes in hematological malignancies (HM) and as a sequela of hematopoietic stem cell transplantation (HSCT) remain under-recognized. These changes may substantially affect patients' quality of life. Therefore, this review systematically evaluated longitudinal neurocognitive changes in patients with HM undergoing HSCT. METHODS: Following PRISMA guidelines, PubMed, Scopus, and CINAHL were searched on October 30, 2025. Longitudinal studies assessing neurocognitive changes in patients with HM undergoing HSCT, with or without healthy controls, were included. Risk of bias was assessed using an adapted National Institutes of Health quality assessment tool for before-after studies. Effect sizes with 95% confidence intervals were calculated to quantify changes in neurocognitive performance. RESULTS: Nine of 2012 studies met the inclusion criteria, with overall moderate study quality. Improvements may occur post-HSCT; however, allogeneic HSCT and myeloablative conditioning were main risk factors identified for persistent cognitive decline. In line with white matter damage, executive function and attention/processing speed impairments likely represent core deficits, which may affect other cognitive impairments. Post-HSCT changes depend on task characteristics, cognitive load, and conditioning intensity. CONCLUSIONS: Future research should emphasize regular neurocognitive assessment to guide cognitive rehabilitation, implement pre-transplant cognitive rehabilitation strategies to mitigate post-HSCT cognitive decline, and enhance treatment outcomes.

Humans

Clinical Trial: Effectiveness and Safety of a Novel Anal Insert Device for Treatment of Faecal Incontinence.

BACKGROUND: Treatment options for medically-refractory faecal incontinence (FI)-including anorectal biofeedback, dextranomer injection, and sacral nerve stimulation-are limited and outcomes are often suboptimal. Anal or vaginal insert devices are infrequently used. AIMS: We evaluated the safety and effectiveness of a new anal insert device (StaySure) in patients with FI. METHODS: Patients with FI for&#x2009;&#x2265;&#x2009;6&#x2009;months and&#x2009;&#x2265;&#x2009;4 moderate or large FI episodes during a 4-week baseline entered a 2-4&#x2009;week fitting/run-in period to individualise device size (10 or 13&#x2009;mm) followed by a 4-week treatment period. Outcomes included effectiveness, safety, and quality of life (QoL). The primary outcome was the proportion achieving a&#x2009;&#x2265;&#x2009;50% reduction in FI frequency. RESULTS: Of 124 enrolled patients, 98, 71, and 61 progressed through the baseline, fitting/run-in, and treatment phases respectively, with few exclusions due to device intolerance. In the intent-to-treat cohort of 59 participants (93% women), mean (SD) number of days with FI declined from 13.2 (7.0) to 6.3 (6.9), and FI weekly episodes declined from 5.4 (6.9) to 2.1 (5.1) (69% reduction; p&#x2009;<&#x2009;0.001) with similar results for both device sizes. The primary endpoint was achieved in 76.3% of participants; 54.2% achieved&#x2009;&#x2265;&#x2009;75% reduction. The FIQoL overall score increased from a mean (SD) of 1.9 (0.6) to 2.3 (0.6) (p&#x2009;<&#x2009;0.001), indicating improved QoL. Improvements in FI frequency, FIQoL exceeded minimal clinically important difference thresholds, confirming clear clinical benefit. No treatment-related serious adverse events were reported. CONCLUSIONS: The StaySure anal insert device is safe, well tolerated, and effective in reducing FI in patients with moderate to severe symptoms refractory to conservative therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03898778.

Adult