Dental caries in primary teeth is common for young children in the United Kingdom. Evidence suggests this is not routinely treated in keeping with recommended guidance. Silver diamine fluoride offers an alternative approach however it is unknown whether it is more clinically effective than usual care in NHS primary dental service. Clinical trials in primary dental care have myriad challenges. The aim of this study was to establish whether conducting a randomised controlled trial to compare silver diamine fluoride to usual care for the treatment of caries in children's primary teeth is feasible. The setting was eight primary dental care sites in Yorkshire and the East Midlands. Children aged 1-8 years old with caries in a primary tooth were randomised in a 1:1 allocation ratio to receive usual care or silver diamine fluoride and followed up for 12 months. Quantitative data were collected at recall and treatment visits pertaining to the feasibility of conducting a definitive trial. This included the ability to recruit, randomise and retain participants and the appropriate outcome measures. Adherence to research processes was also recorded. Qualitative interviews were conducted with children, parents and dental professionals to explore the acceptability of the research processes and intervention. Quantitative data were analysed through descriptive statistics, qualitative data were analysed using thematic analysis. Eight sites recruited 54 children in total. The recruitment rate from those eligible was 94%, however the recruitment period was slow and the target was not met. The majority of children were retained (74%), but there was intermittent missing data owing to missed clinical appointments. For 11 patients there was deviation from the allocated treatment, with a tendency for more children to receive silver diamine fluoride than allocated owing to lack of co-operation with usual care. There was tension between research aims and equipoise, and clinician and family treatment preferences. Candidate outcome measures were well completed, except for caries progression. Although silver diamine fluoride appeared to be potentially beneficial for use with this cohort of patients in primary care, further work is needed to inform the design of a definitive trial. Registration is at Clinaltrials.gov (NCT06092151, 23/10/2023).
Sexually transmitted infections (STIs) remain a significant global health burden. In Saudi Arabia, limited awareness, stigma, and inconsistent provider competence impede effective prevention and counseling. This study aimed to assess primary care physicians' (PCPs) competence and physician perceived barriers (attitudes) in STI prevention and counseling across Saudi primary care. A cross-sectional survey was conducted from July 2024 to July 2025 among PCPs in Saudi Arabia. Data were collected using a validated, self-administered electronic questionnaire through social media and official email lists. The survey collected sociodemographic data, STI-related practices (including risk assessment, counseling, and testing), and perceived barriers to care. Practices were scored as continuous variables using a 5-point Likert scale (Never to Always), while perceived barriers were assessed across five domains using a 5-point Likert scale (Strongly Disagree to Strongly Agree) and subsequently dichotomized into 'high' or 'low' based on the median score. Descriptive statistics summarized responses, and non-parametric tests evaluated group differences. Multivariable logistic regression was used to identify factors associated with higher practice scores, while logisitc regression identified predictors of high perceived barriers. Both models included age, gender, years of experience, practice sector, and number of STI patient consultations as independant variables and confounders. A total of 133 physicians participated (55% male, 45% female); most were aged 36-45 years (40%) and practicing in primary healthcare centers (38%) or governmental hospitals (35%). Training in STI counseling was most often obtained during residency (38%), though 12% reported no formal training. Clinical exposure was limited, with 51% managing 1-5 STI cases in the past six months. Mean scores were 2.59 for risk assessment, 3.76 for counseling, 3.75 for testing, and 3.64 for attitudes. Multivariable analysis revealed that the absence of recent clinical exposure to STI cases (managing zero cases in the past 6 months) was significantly associated with a lower risk assessment (β = -0.888, p = 0.0031), testing (β = -0.951, p = 0.0024), and attitude scores (β = -0.281, p = 0.0319). Counseling scores were significantly higher among physicians with 16-20 years' experience (β = 1.333, p 0.0108). PCPs in Saudi Arabia demonstrate moderate STI-related competence, with gaps in risk assessment and pervasive barriers to counseling. Targeted continuing education, structured training in sexual health, and standardized screening protocols are needed to enhance STI prevention and care in primary care settings.
To evaluate the efficacy and safety of rivaroxaban and low molecular weight heparin (LMWH) for the prevention of postoperative venous thrombosis (VTE) following primary unilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA). A total of 11,686 patients who received rivaroxaban and LMWH (6,110 cases of THA and 5,576 cases of TKA) between January 2014 and November 2017 in 26 large teaching hospitals were enrolled. The patients were divided into two groups according to the postoperative use of anticoagulant drugs, including 4,591 cases in the rivaroxaban group (2,288 cases of THA and 2,303 cases of TKA) and 7,095 cases in the LMWH group (3,822 cases of THA and 3,273 cases of TKA). The incidence of deep vein thrombosis (DVT) in the lower extremities, and pulmonary embolism (PE), were analyzed as indicators of efficacy. The incidences of postoperative bleeding events, total blood loss (TBL), and transfusion rate, were considered as safety indicators. The overall incidence of DVT was 0.40% (47/11,686) in patients undergoing primary THA/TKA. The incidence of DVT in the rivaroxaban group was 0.74% (34/4591); this was significantly higher than that in the LMWH group (0.18%; 13/7095) (OR 4.07, 95% CI 2.14-7.71;p < 0.001). In the THA subgroup, the incidence of DVT in the rivaroxaban group was 0.52% (12/2288 cases); this was significantly higher than that in the LMWH group 0.10% (0.10%; 4/3822) (p = 0.002). In the TKA subgroup, the incidence of DVT was 0.96% (22/2303 cases) in the rivaroxaban group and 0.27% (9/3273 cases) in the LMWH group (p < 0.001). Only one patient treated with LMWH after TKA was diagnosed with symptomatic PE in this study. There was no significance difference in terms of safety between rivaroxaban and LMWH (p > 0.05) in terms of the incidence of bleeding events and TBL. However, in the TKA subgroup, TBL was significantly higher in the rivaroxaban group than in the LMWH group (915 ± 514 ml vs. 872 ± 487 ml, p = 0.030). With regards to transfusion rate, patients in the rivaroxaban group had a significantly higher need for blood transfusion than those in the LMWH group (OR 3.30,95% CI 2.88-3.78;p < 0.001). Subgroup analysis revealed that the transfusion rates in the THA and TKA sub-groups were both higher in the rivaroxaban group (14.8%, 14.2%) than those in the LMWH group (6.5%, 3.0%) (p < 0.001). For patients following primary unilateral THA/TKA, LMWH is superior to rivaroxaban in terms of the prevention of symptomatic in-hospital DVT' and the control of TBL and transfusion rates. However, the efficacy of these drugs for controlling bleeding events was similar when compared between the two groups.
Understanding ecosystems functioning under frequent climatic perturbations is central to predicting ecosystem stability. While studies suggest that stable ecosystems can buffer against climate extremes, there is no agreement on whether this stability arises from their resistance (ability to absorb shock) to perturbations, resilience (capacity to recover) towards disturbances, or a combination of both. Using annual net primary productivity (NPP) and Standardized Precipitation Evapotranspiration Index (SPEI) and aridity index (AI), we investigated the (i) spatiotemporal changes of NPP, (ii) correlation between NPP, SPEI and AI, and (iii) resistance and resilience of meadow steppe, typical steppe, steppe desert, and desert steppe in Inner Mongolia from 2000-2019. Despite substantial interannual variability, all grassland types showed an upward trend in NPP, ranging from 1.21 g C m-2 yr-1 in desert steppe to 4.54 g C m-2 yr-1 in meadow steppe. The highest NPP (g C m-2 yr-1) was observed in meadow steppe (251), followed by typical steppe (160), steppe desert (95), and desert steppe (83). NPP increased significantly with increasing SPEI values across all grassland types, and with rising AI in steppe desert and desert steppe. Partial correlation analysis controlling for CO2 confirmed that NPP remained significantly and positively correlated with precipitation across all grassland types. Species richness ranged between 9 and 14 in meadow steppe, 7 and 17 in typical steppe and 5-10 in steppe desert. The measured NPP showed an increasing trend with rising species richness across these three grassland types, demonstrating a positive diversity-productivity relationship. Vegetation exhibited lower (higher) resistance against dry (wet) climatic conditions and higher (lower) resilience towards dry (wet) climatic conditions for all grasslands except for desert steppe. Typical steppe, meadow steppe and steppe desert are susceptible to extreme dry climate as these grasslands showed lower resistance against extreme dry climate. However, the higher resilience of these grasslands after extreme dry climate highlights that they recover faster after dry conditions compared to the recovery after wet conditions. The observed increase in vegetation productivity and differing stability has practical implications for pastoralists, landscape managers, and conservationists for grassland management. The demonstrated positive diversity-productivity relationship suggests maintaining greater species richness could buffer productivity losses during climate extremes, while the NPP-AI correlations in steppe desert and desert steppe offer early warning indicators for drought preparedness.
The imminent climate crisis calls for the development of truly sustainable alternatives in virtually every aspect of human life. The photosynthetic production of chemicals like isoprene, a critical precursor for wide ranging applications, presents a promising alternative to conventional petroleum-based processes. While cyanobacteria can offer the ability for direct CO2 to isoprene conversion, highly efficient strains are required to reduce costs and resource usage. In this study, we enhanced isoprene productivity in the model cyanobacterium Synechocystis sp. PCC 6803 by engineering the primary metabolism of an isoprene producing strain. We inactivated synthesis of the carbon and energy storage polymer polyhydroxybutyrate (PHB) and increased isoprene synthase copy number in a previously published deletion mutant of PirC (sll0994), a recently discovered regulator involved in the fate of newly fixed carbon during limited nutrient supply. The engineered strains achieved an isoprene production of 278 µg*L- 1*OD- 1*h- 1 and showed elevated productivity under fluctuating nitrogen supply, ultimately resulting in significantly enhanced nitrogen use efficiency for isoprene production. As nitrate represents the ingredient with the highest cost contribution and climate impact in conventionally used cyanobacterial growth media, the presented strategy could reduce cost and environmental footprint without impeding performance for a wide array of compounds sustainably produced with cyanobacteria.
The introduction of neoadjuvant and perioperative immunotherapy has broadened treatment options for resectable non-small cell lung cancer (NSCLC). However, clinical benefit varies across subpopulations, and standard linear models cannot fully capture the complex feature interactions and trial-level differences found in aggregate data. We applied an integrated framework combining multilevel meta-regression with an inverse-variance weighted eXtreme Gradient Boosting (XGBoost) algorithm. SHapley Additive exPlanations (SHAP) were used to interpret the model and identify efficacy variance drivers across seven randomized controlled trials. Multilevel meta-regression demonstrated that event-free survival (EFS) benefit correlated positively with PD-L1 expression, peaking in the ≥50% subgroup (adjusted HR = 0.44, 95% CI: 0.33--0.57). XGBoost-SHAP analysis revealed trial-level variance as the dominant driver of heterogeneity. Among subgroup-level clinical covariates, a non-linear U-shaped PD-L1 predictive pattern (<1% and ≥50%), squamous cell carcinoma (SCC) histology (HR = 0.53, 95% CI: 0.43--0.65), and smoking history emerged as primary predictors. Synthesizing these signatures into a hypothesis-generating subgroup stratification framework indicated that SCC and PD-L1-negative (<1%) non-squamous cohorts benefit from continuous perioperative blockade. Conversely, exploratory analyses suggested that PD-L1-positive (≥1%) non-squamous tumors achieved maximal observed benefit from exclusively neoadjuvant regimens (HR = 0.50). Our results suggest that for PD-L1-positive non-squamous cases, the added benefit of extended adjuvant therapy may be limited. However, given our reliance on aggregate data and trial-level imbalances, these findings remain hypothesis-generating and should not alter current clinical practice. Rather, they offer an exploratory framework to inform patient selection for future de-escalation trials.
Primary cardiac diffuse large B-cell lymphoma (DLBCL) is an exceptionally rare entity in the published literature. We have reported here the case of a 73-year-old Chinese man who presented with intermittent chest tightness as the chief complaint. Echocardiography identified a pedunculated, moderately echogenic mass (approximately 49 × 36 mm) within the left atrium, attached to the interatrial septum and mobile with the cardiac cycle, initially suggestive of a myxoma. The patient underwent surgical resection of the cardiac mass without any preoperative diagnosis. Histopathological examination confirmed DLBCL. Notably, the patient received neither postoperative radiotherapy nor chemotherapy. At nearly 3 years of follow-up, he remains alive with a favorable prognosis and sustained disease-free survival.
Accurate prognostication in locally advanced oesophageal squamous cell carcinoma (LA-ESCC) remains a significant clinical challenge. This prospective study aimed to compare the predictive value of fluorine-18 fluorodeoxyglucose (18F-FDG) and fluorine-18 fluorothymidine (18F-FLT) positron emission tomography/computed tomography (PET/CT) regarding long-term clinical outcomes. Between June 2018 and July 2019, 31 patients with LA-ESCC were prospectively enrolled and underwent both 18F-FDG and 18F-FLT PET/CT scans prior to or during initial therapy. Quantitative parameters, including maximum standardized uptake value (SUV max), minimum SUV (SUV min), mean SUV (SUV mean), tumour metabolic volume (MTV), total lesion glycolysis (TLG), and total lesion 18F-FLT expression (TLT), were measured for primary tumours and regional lymph nodes. Progression-free survival (PFS) and overall survival (OS) were analysed using Cox univariate regression, receiver operating characteristic (ROC) curve analysis, and Kaplan-Meier survival estimates. In 18F-FLT PET/CT, primary tumour parameters (SUV max, SUV mean, TLT) and all lymph node parameters significantly distinguished between favourable and poor PFS groups (all P <0.05). Primary tumour SUV max, SUV mean, and all lymph node parameters demonstrated a negative correlation with both PFS and OS. Specifically, lymph node SUV max (PFS: hazard ratio (HR)=1.65, 95% confidence interval (CI):1.23-2.19, P =0.002; OS: HR = 1.81, 95% CI:1.29-2.55, P <0.001) and SUV mean showed strong predictive value. In contrast, for 18F-FDG PET/CT, only lymph node MTV differed significantly between PFS groups (P =0.03), with no parameters showing significant prognostic correlation. ROC analysis indicated that 18F-FLT lymph node SUV max and SUV mean yielded the highest predictive accuracy for PFS (area under the curve (AUC): 83.8% and 84.2%, respectively) and OS (AUC: 79.3% for both). 18F-FLT PET/CT may offer superior prognostic value compared to 18F-FDG PET/CT for long-term survival prediction in LA-ESCC. Parameters derived from metastatic lymph nodes, particularly SUV max and SUV mean, may serve as potential biomarkers for poor clinical outcomes, independent of imaging timing.
Cardiovascular-kidney-metabolic (CKM) syndrome has emerged as a major global health burden and driver of cardiovascular disease (CVD), the leading cause of death worldwide. Effective management of CKM depends on timely identification of underlying risk factors. Nevertheless, participation rates in primary care-based screenings are low. Consequently, CKM syndrome oftentimes remains undetected until organ damage is clinically present. Community pharmacies offer an accessible, yet underused, setting to enhance early detection. APOSCREEN-1 evaluates the feasibility and diagnostic yield of a pharmacy-based multi-parametric screening for cardiovascular-kidney-metabolic health. APOSCREEN-1 is a prospective single-arm clinical trial conducted in 20 community pharmacies in the German state of Schleswig-Holstein. Adults (n = 1000) aged ≥ 40 years with predefined risk criteria are included. Participants undergo standardized point-of-care testing (glycated hemoglobin, lipid profile, urinary albumin, blood pressure). Additionally, clinical history is assessed and results are transmitted to the study center via an online platform. Patients meeting pre-defined thresholds of the tested parameters are followed up by confirmatory laboratory testing at the study center or at the participants' general practitioner. Primary outcomes include completion rate, implementation metrics from the pharmacy perspective, and the number needed to screen to detect unknown or insufficiently managed cardiometabolic risk factors. Secondary outcomes comprise participant metrics, diagnostic metrics of the screening, evaluation of the clinical impact. This study aims to address the unmet need for scalable prevention of CVD by identification of CKM syndrome risk factors outside traditional primary care settings. Evidence on feasibility, acceptance, and diagnostic benefit may support the use of community pharmacies as an additional access point for early CKM syndrome detection. Future interventional studies will be required to evaluate structured follow-up pathways and long-term effectiveness. This study was registered with the German trial registry (Deutsches Register klinischer Studien) on 29.01.2026, under trial number DRKS00039149.
To evaluate 1-year clinical and functional outcomes, as well as donor-site morbidity based on quadriceps muscle morphology, after primary single-bundle ACLR using a quadrupled RF tendon autograft. Patients who underwent primary single-bundle ACLR using a quadrupled RF tendon autograft with adjustable suspensory fixation between December 2024 and April 2025 were retrospectively reviewed. Clinical outcomes were assessed using the International Knee Documentation Committee Subjective Knee Form (IKDC), Marx Activity Scale, KT-1000 arthrometer side-to-side difference, and pivot-shift test. Quadriceps muscle volumes, including RF, vastus medialis (VM), vastus lateralis (VL), and vastus intermedius (VI), were measured using magnetic resonance imaging (MRI) at one year postoperatively. Isokinetic strength testing at 60°/s and 240°/s and hop performance tests were performed to determine limb symmetry indexes (LSI). A total of 54 patients were evaluated with a mean follow-up of 15.7 ± 4.2 months. The mean IKDC score was 84.1 ± 9.7, the mean Marx Activity Scale score was 7.1 ± 3.2, and the mean side-to-side anterior tibial translation difference was 1.8 ± 1.2 mm. All quadriceps muscle volumes were significantly lower in the operated limb than in the contralateral limb (p < 0.001). Mean deficits were 9.63% for RF, 8.52% for VL, 7.95% for VI, and 8.08% for VM. No significant difference was observed among the percentage deficits of the four muscles (F = 1.701, p = 0.170). LSI values exceeded 90% in all evaluated strength and functional parameters. No significant side-to-side differences were found in most isokinetic and hop tests, except for 240°/s extension strength (p = 0.03) and triple-hop performance (p < 0.001). Primary ACLR using a quadrupled RF tendon autograft resulted in favourable one year clinical and functional outcomes with restoration of limb symmetry. Quantitative MRI analyses demonstrated that RF graft harvest did not result in selective RF muscle volume loss or clinically relevant strength deficit at one year postoperatively.
Reliable hygienic hand-disinfection is essential for infection prevention and control. It remains unclear whether a short VR training module improves objectively assessed procedural performance compared with conventional instruction. This single-center, parallel-group randomized controlled trial examined first-opportunity hand-disinfection performance in an Objective Structured Clinical Examination (OSCE) after VR training versus a video control. In 2025, first-year nursing students at a single Austrian University of Applied Sciences were randomized (1:1) to a 20-minute VR training module with contamination visualization feedback or a time- and headset-matched instructional video control without interactivity. Randomization used block allocation (blocks of six); instructions were standardized via audio playback. Three days later, students completed a routine five-station OSCE. Hygienic hand-disinfection was required at the beginning of each of five OSCE stations and was documented within routine station checklists. Hand-disinfection ratings from the five stations were extracted from routine OSCE checklists and coded (0 = incorrect, 1 = partially correct, 2 = correct). The preregistered primary endpoint was station 1 performance. The primary hypothesis was tested with adjusted proportional-odds regression, adjusting for age, gender, and prior hygiene-course grade as a baseline indicator of hygiene-related academic performance; all other analyses were exploratory. Of 128 randomized students (VR n = 65; control n = 63), all had available station 1 hand-disinfection scores, which constituted the primary outcome. One value was missing for the prior hygiene-course grade covariate, yielding N = 127 for adjusted models. At station 1, fully correct performance occurred in 52/65 (80.0%) in VR versus 15/63 (23.8%) in control. VR training was associated with markedly better first-opportunity performance (adjusted OR = 11.16, 95% CI [4.95, 25.14], p = 5.9 × 10- 9), supported by a binary pass/fail sensitivity analysis (adjusted OR = 6.06, 95% CI [1.84, 19.92]). Exploratory analyses suggested higher performance across stations, with group differences varying by station. No harms or adverse events were observed during the trial. A short VR training module for hand-disinfection with contamination visualization was associated with better first-opportunity OSCE hand-disinfection performance compared with a headset-delivered instructional video control. This suggests that short, feedback-rich VR training may support immediate procedural readiness under standardized assessment conditions. This study was preregistered within a larger longitudinal project and later registered as a stand-alone study in the Open Science Framework (OSF) (https://doi.org/10.17605/OSF.IO/3B6SC). Not applicable.
[68Ga]Ga-FAPI-04 targets FAP overexpressed in pancreatic cancer microenvironment. This study compared diagnostic efficacy and clinical impact with [18F]FDG PET/CT in pancreatic cancer. Of 97 suspected pancreatic cancer patients (58 males; mean age 63.0 ± 10.1 years), 88 were confirmed as pancreatic cancer (57 by pathology, 31 by imaging follow‑up). [68Ga]Ga-FAPI-04 PET/CT showed significantly higher SUVmax than [18F]FDG PET/CT in primary lesions (10.2 ± 3.5, 95%CI: 9.320-11.126 vs. 6.1 ± 3.8, 95%CI: 5.092-7.152; p = 0.001) and lymph node metastases (4.1 ± 2.4, 95%CI: 3.718-4.559 vs. 3.3 ± 2.3, 95%CI: 2.845-3.714; p = 0.001), with superior AUCs for primary tumors and lymph nodes(0.851, 95% CI: 0.735-0.981 vs. 0.802, 95% CI: 0.354-0.803; p = 0.001) (0.867, 95% CI: 0.827-0.907 vs. 0.701, 95% CI: 0.641-0.761; p = 0.001). The T/B ratio of bone and visceral metastases was higher in [68Ga]Ga-FAPI-04 PET/CT than [18F]FDG PET/CT(4.7 ± 3.1, 95%CI: 4.108-5.245 vs. 2.5 ± 1.6, 95%CI: 2.231-2.835; p = 0.001) with superior AUC(0.938, 95% CI: 0.912-0.964 vs. 0.919, 95% CI: 0.886-0.951; p = 0.040), as were liver (5.0 ± 4.0, 95%CI: 3.706-6.284 vs. 2.7 ± 1.3, 95%CI: 2.211-3.131; p = 0.001), peritoneal (5.4 ± 3.3, 95%CI: 4.318-6.482 vs. 3.0 ± 2.1. 95%CI: 2.211-3.745; p = 0.001) and other organ metastases (4.4 ± 2.5, 95%CI: 3.756-5.035 vs. 2.7 ± 1.7, 95%CI: 1.379-2.254; p = 0.001). [68Ga]Ga‑FAPI‑04 SUVmax and TBR were positive predictors for primary tumors (SUVmax: OR = 1.951, 95%CI: 1.286-2.960, p = 0.004) and nodal metastases (SUVmax: OR = 4.199, 95%CI: 2.970-5.939, p = 0.001; TBR: OR = 14.502, 95%CI: 7.228-29.095, p = 0.001). For bone and visceral metastases, both tracers were positive predictors, but [68Ga]Ga‑FAPI‑04 SUVmax (OR = 2.925, 95%CI: 2.048-4.177, p = 0.003) and T/B ratio (OR = 3.520, 95%CI: 2.311-5.362, p = 0.001) outperformed [18F]FDG (SUVmax: OR = 1.901, 95%CI: 1.308-2.761, p = 0.003; T/B ratio: OR = 2.480, 95%CI: 1.488-4.136, p = 0.001). Furthermore, [68Ga]Ga-FAPI-04 achieved higher accuracy (93.2% vs. 72.7%, p = 0.007), revised the staging of 7 patients and altered the treatment (surgical resection to unresectable) in 6 patients. Limitations include single‑center, short follow‑up, small subgroups (e.g., recurrent lesions) and incomplete pathologically confirmation. [68Ga]Ga-FAPI-04 PET/CT suggested potentially better diagnostic performance to [18F]FDG PET/CT and improves staging and clinical decision-making in pancreatic cancer, suggesting potential clinical value.
With improved intensive care unit (ICU) survival rates, the number of patients with post-intensive care syndrome (PICS) is on the rise. The Society of Critical Care Medicine (SCCM) recommends screening within 2-4 weeks post-discharge. However, in China, most ICU survivors rely on family caregivers, while data on caregiver burden specifically at 2 weeks post-discharge remain scarce. This cross-sectional study aimed to identify the factors influencing family caregiver burden in PICS patients 2 weeks after hospital discharge. A cross-sectional study was conducted in the intensive care unit (from March 2024 to June 2025). Consecutive patients with post-intensive care syndrome and their primary family caregivers were included 14 days after discharge. Potential predictive factors were collected using a self-made standardized questionnaire and the Zarit Burden Interview Scale. Multivariate ordinal logistic regression analysis was used to identify factors associated with the severity of caregiver burden. Conducted at a tertiary hospital from March 2024 to June 2025, the study included 299 patient-primary caregiver pairs. Using the Zarit Burden Interview (ZBI), the median caregiver burden score was 38.0 (IQR:25.0, 52.0), with 26.1% reporting minimal/no burden, 34.1% mild to moderate, 25.4% moderate to severe, and 14.4% severe burden. Multivariate ordinal logistic regression identified seven independent risk factors: caregiver age ≤ 45 years (OR = 3.196, 95% CI = 1.351-7.591), rural residence (OR = 2.894, 95% CI = 1.089-7.723), Dedicated care 2 weeks after ICU (OR = 6.844, 95% CI = 3.029-15.482), patient not returning to work (OR = 3.019, 95% CI = 1.459-6.251), caregiver cohabiting with spouse and children (OR = 6.758, 95% CI = 1.166-39.200), presence of other stressors (OR = 2.228, 95% CI = 1.155-4.305), and caregiver cohabiting with the patient (OR = 3.116, 95% CI = 1.483-6.546). Protective factors included caregiver being married/cohabiting, patient's ICU stay ≤ 30 days, first ICU admission, and prognosis aligning with expectations (all p < 0.05). Two weeks post-discharge, family caregivers of PICS patients predominantly bear mild to moderate burden; multivariate analysis identifies key risk and protective factors, addressing the gap in early-stage evidence and providing a basis for targeted clinical interventions. ChiCTR2500100968 (https://www.chictr.org.cn); retrospectively registered on April 17, 2025.
Cytokeratin 19 fragment (CYFRA 21 - 1) has shown diagnostic utility in oral squamous cell carcinoma (OSCC), but its prognostic value and treatment-induced dynamics remain unclear. This study evaluated baseline and early post-treatment salivary and serum CYFRA 21 - 1 concentrations in patients with OSCC to assess associations with clinicopathological characteristics and recurrence-free survival. We prospectively enrolled 40 patients with primary, resectable OSCC and measured salivary and serum CYFRA 21 - 1 by ELISA before surgery and 14 days post-operatively. The primary outcome was recurrence-free survival. Pretreatment salivary CYFRA 21 - 1 was higher in T3-4 versus T1-2 tumors (p = 0.033) and associated with nodal metastasis (p = 0.040). Surgical resection significantly reduced CYFRA 21 - 1 levels. However, larger absolute reductions in salivary levels (≥ 0.74 ng/mL) predicted higher recurrence risk (OR = 6.09), as did elevated baseline salivary CYFRA 21 - 1 (≥ 2.66 ng/mL; OR = 9.35). Both metrics independently predicted recurrence-free survival in multivariate Cox regression (HR = 3.00-4.10), while standard clinical factors including TNM stage and nodal status did not. Salivary and serum CYFRA 21 - 1 correlated weakly to moderately (r = 0.33, p < 0.05). Baseline salivary CYFRA 21 - 1 and large post-treatment reductions independently predicted OSCC recurrence, outperforming TNM staging in multivariate analysis. Larger CYFRA 21 - 1 reductions were associated with increased relapse risk, potentially reflecting aggressive tumor biology, though this counterintuitive finding requires validation in larger independent cohorts before definitive mechanistic conclusions can be drawn. Monitoring CYFRA 21 - 1 kinetics may provide biologically informed prognostication beyond anatomical classification. Salivary CYFRA 21 - 1 offers a non-invasive biomarker for postoperative risk stratification that could guide personalized surveillance strategies, enabling early identification of high-risk patients who may benefit from intensified follow-up or adjuvant therapy.
This study evaluated the effectiveness of a brief, Theory of Planned Behavior-based educational program on weight management and related health outcomes among university employees. In this quasi-experimental study conducted at two major universities in Erbil, Iraq, 200 employees with a body mass index (BMI) ≥ 25 kg/m² self-selected into an intervention (n = 100) or control (n = 100) group. The intervention consisted of five individual 35-40-minute sessions delivered over 12 weeks and covered obesity awareness, culturally adapted nutrition education, physical activity, and behavior-change strategies. The control group received only standard written materials. Primary outcomes were changes in body weight, BMI, and waist circumference. Secondary outcomes included lipid profile, fasting glucose, quality of life (Impact of Weight on Quality of Life-Lite [IWQOL-Lite]), dietary quality, and physical activity. All assessments were performed at baseline and 12 weeks. The intervention was associated with a mean weight loss of 7.46 kg (95% CI 6.44-8.48) compared with a gain of 0.58 kg in the control group (adjusted difference - 8.04 kg; p < 0.001; Cohen's d = 2.40). 79% of intervention participants lost ≥ 5% of their initial body weight (versus 0% in controls), and 41% lost ≥ 10%. Significant improvements were also observed in BMI, waist circumference, lipid profile, quality of life, and dietary quality (all p < 0.001; d > 1.8). Mediation analysis indicated that improvement in dietary quality accounted for 82% of the observed association between group assignment and change in BMI. A brief, low-cost, culturally adapted educational intervention delivered in the workplace was associated with exceptionally large weight loss, cardiometabolic benefits, and psychosocial gains, with perfect retention. These findings suggest that this model may offer a promising approach for obesity management in Middle Eastern settings. However, confirmation in randomized controlled trials with longer follow-up is required before firm conclusions regarding scalability and effectiveness can be drawn. The study was not prospectively registered in a clinical trial registry because it employed a quasi-experimental design with participant self-selection rather than random allocation. However, the full study protocol including all primary and secondary outcomes, eligibility criteria, intervention details, and the statistical analysis plan was finalized, approved by the Hawler Medical University Ethics Committee (reference HMU-REC-2024-18, 15 September 2024), and locked prior to the start of participant recruitment and data collection. No outcomes were added, removed, or modified after data inspection, and no post-hoc analyses were conducted beyond those pre-specified in the protocol. The manuscript adheres fully to the TREND reporting standards for non-randomized evaluations.
Direct oral anticoagulants (DOACs) are commonly prescribed for the management of thromboembolic diseases and are known to increase the risk of bleeding. Renal impairment is a risk factor for bleeding in DOACs users, making renal function access essential for community pharmacists during the prescription review and dispensing process. However, community pharmacists often have limited access to patients' renal function information. Giving Community Pharmacists full access to the renal function information could help to mitigate this preventable part of the risk of bleeding by optimizing DOACs choice and dosage, thereby helping to reduce the risk of bleeding events. This study aims to assess the impact of providing Community Pharmacists with access to patients' renal function information when dispensing DOACs on the occurrence of clinically relevant bleeding events three months after dispensing. A prospective, comparative, randomized, cluster, multicenter trial involving 96 community pharmacies, allocated into two groups: intervention (systematic access to renal function) and control (usual care). A total of 1920 patients will be included over a 24-month period and followed for 6 months. The primary endpoint is the occurrence of clinically relevant bleeding-major and nonmajor-occurring within three months after DOACs dispensing. Secondary endpoints include detail of pharmacist interventions and an assessment of the feasibility of providing renal function access to Community Pharmacists. This study will assess the clinical impact of providing Community Pharmacists with access to renal function information. The findings have the potential to inform best practices and drive meaningful changes in ambulatory pharmaceutical care. The trial is registered with ClinicalTrials.gov: NCT06739603, December 17th, 2024. https://clinicaltrials.gov/study/NCT06739603?term=NCT06739603&rank=1.
Human coronavirus NL63 (hCoV-NL63) is a major pathogen associated with pediatric acute respiratory tract infections. Although most infections are mild, severe lower airway complications have been increasingly reported. The aim of this study was to investigate the clinical and flexible bronchoscopy (FB) findings, as well as the interventional value, in young infants with hCoV-NL63-associated necrotizing laryngotracheobronchitis (NLTB). A retrospective case series was conducted at a tertiary pediatric intensive care unit between August 2025 and September 2025. Clinical data, including demographics, symptoms, imaging, FB findings, etiological test results, treatment strategies, and clinical outcomes of 3 young infants with confirmed hCoV‑NL63‑related NLTB were systematically analyzed. All patients presented with progressive hoarseness, dyspnea, stridor, and upper airway obstruction as primary manifestations. FB demonstrated characteristic subglottic mucosal necrosis, ulceration, and airway stenosis in all cases. Urgent FB‑guided endotracheal intubation was successfully performed to secure the airway. Bronchoalveolar lavage fluid (BALF) examination confirmed hCoV‑NL63 infection, with concurrent Streptococcus pneumoniae detected in all samples. After comprehensive treatment including systemic glucocorticoids, broad‑spectrum antibiotics, airway management, and supportive care, all young infants showed significant clinical improvement, survived without serious complications, and were discharged successfully. hCoV-NL63 may be associated with severe NLTB in young infants. FB may play a valuable and important role in early diagnosis, airway evaluation, and guided intubation. Multimodal therapy achieves favorable short‑term outcomes. Clinicians should strengthen awareness of this rare but severe entity to avoid delayed diagnosis and inappropriate intervention. This study is hypothesis-generating only, and larger studies are needed to confirm these results. Not applicable.
Pharmacists and their teams can undertake pharmaceutical public health roles during outbreaks within the World Health Organization (WHO) emergency cycle of prevention, preparedness, response, and recovery. These may be at micro- (individual), meso- (regional or organisational) or macro- (national) levels. The primary outcome was to identify pharmacy team members' roles in outbreaks (excluding COVID-19) and classify by WHO emergency cycle phase and intervention level. We conducted a rapid systematic review (PROSPERO: CRD42024617152) in Embase, Medline, and SCOPUS databases including articles published from 2014 to Feb 2025. After duplicate removal, titles/abstracts and full texts were screened, extracted and assessed for bias by one reviewer, with 10% second-checked. Thematic synthesis was used and described narratively to reflect variability in the studies. From 161 articles across all WHO regions, 145 distinct thematically derived role categories were identified. Most were in the response phase (46%), followed by prevention (29%), preparedness (15%), and recovery (10%). Roles were primarily at meso-level (37%) and micro-level (35%), with fewer at macro-level (28%). 34% of the articles reported contributions related to health inequalities. Reported barriers were clustered into five themes: knowledge/training gaps, regulatory restrictions, resource and infrastructure constraints, communication, and cultural factors. Pharmacy team members have roles during non-COVID outbreaks across all stages of the WHO emergency cycle at all levels. However, their contributions are less well documented in recovery and at macro-level. Integrating pharmacy roles into emergency frameworks, supported by regulatory reform, funding, and training, may support health-system resilience, and reduce health inequalities.
This study aimed to identify clinical factors associated with early motor recurrence after unilateral lateral rectus recession with medial rectus plication (RP) in children with basic-type intermittent exotropia (IXT). This retrospective cohort study enrolled children with basic-type IXT who underwent unilateral RP between January 2022 and December 2023. The primary outcome was early motor recurrence, defined as an exodeviation greater than 10 prism diopters (PD) at near at 6 months postoperatively. Early motor success was defined as horizontal exodeviation or esodeviation of 10 PD or less. Deviation at distance and near, fusion, and stereopsis were evaluated at predefined postoperative time points. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were used to assess factors associated with early recurrence and final motor outcomes. Ninety-one patients were included (mean age, 8.10 ± 3.06 years; mean follow-up, 16.81 months). Thirty-one patients met criteria for early motor recurrence, and 60 achieved early motor success. The early recurrence group had significantly larger residual exodeviation at distance and near during the first postoperative week (P < 0.05). In adjusted logistic regression analyses, both near and distance deviations within the first postoperative week were independently associated with early motor recurrence at 6 months (near: OR = 0.738, 95% CI 0.609-0.895, P = 0.002; distance: OR = 0.736, 95% CI 0.606-0.893, P = 0.002) and with final motor failure (near: OR = 0.798, 95% CI 0.683-0.932, P = 0.004; distance: OR = 0.796, 95% CI 0.681-0.930, P = 0.004). Alignment at 6 months showed stronger adjusted associations with final motor outcome at both near and distance. ROC analysis showed moderate discriminative performance for near deviation within 1 week in identifying early recurrence (AUC = 0.7315) and stronger discrimination for near deviation at 6 months in identifying final motor outcome (AUC = 0.8461); these thresholds require external validation. At final follow-up, fusion was more frequent in the early motor success group (P = 0.011). Among children with basic-type IXT undergoing unilateral RP, early postoperative alignment at near and distance was associated with early motor recurrence and final motor failure. Alignment at 6 months showed stronger associations with final motor outcome and should be interpreted as a mid-term prognostic marker rather than an independent early predictor. These findings support careful monitoring of near and distance alignment during the first 6 postoperative months, while acknowledging that the proposed cutoff values require validation in larger, independent cohorts.
To compare optical coherence tomography (OCT) image quality obtained on postoperative day 1 under intraocular gas tamponade using four OCT devices, including two swept-source OCT (SS-OCT) and two spectral-domain OCT (SD-OCT) systems. This retrospective study included 30 consecutive eyes of 30 patients who underwent pars plana vitrectomy with gas tamponade between June 2025 and February 2026. On postoperative day 1, OCT imaging was performed using four devices: two SS-OCT systems (DRI OCT Triton and PLEX Elite 9000) and two SD-OCT systems (RTVue XR Avanti and SPECTRALIS OCT). OCT image quality was graded using a 5-point scale by two masked graders, and the mean score was used for analysis. The primary analysis compared image quality scores among devices in 25 eyes with macular hole using the Friedman test with Bonferroni correction. The mean patient age was 70.0 ± 8.7 years, and 13 patients (43.3%) were male. The median (interquartile range) image quality scores in macular hole cases (n = 25) were 5.0 (4.0-5.0) for Triton, 5.0 (4.0-5.0) for Plex Elite, 4.0 (4.0-5.0) for Avanti, and 2.0 (1.0-3.0) for Spectralis. Image quality scores differed significantly among the four devices (Friedman test, p < 0.001). Under intraocular gas tamponade, the SD-OCT device Avanti demonstrated relatively preserved image quality. These findings suggest that device-specific acquisition characteristics, beyond wavelength differences, substantially influence OCT image quality in gas-filled eyes. These findings may assist clinicians in selecting appropriate OCT devices for reliable postoperative assessment under gas tamponade.