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Chronic pain is a growing global public health challenge and the leading cause of years lived with disability. It significantly impacts various aspects of daily life, including participation in working life, resulting in increased sick leave and substantial burdens at both the personal and societal levels. Person-centered care (PCC) is a practiced ethic that recognizes the patient as a partner in care. Partnership is established through incorporating the person's narrative, shared decision-making, and documentation of jointly agreed goals. Remotely delivered PCC interventions have been shown in other studies to improve self-efficacy and facilitate return to work among persons on sick leave. However, little is known about how self-efficacy and sick leave are affected when a PCC intervention is delivered remotely to persons with chronic pain. This study aimed to evaluate the efficacy of a home-based person-centered intervention consisting of telephone support and an eHealth platform among persons on sick leave due to chronic pain. A 2-arm, nonblinded randomized controlled trial was conducted. Participants aged 18 to 65 years on sick leave due to chronic, nonmalignant pain lasting more than 3 months were recruited from 10 primary health care centers in Gothenburg, Sweden. Participants were randomly allocated 1:1 to either the control group or the intervention group. Both groups received usual care; the intervention group additionally participated in a 6-month PCC intervention via telephone and an eHealth platform. The primary outcome was a composite score consisting of change in general self-efficacy and sick leave at the 6-month follow-up. Self-efficacy was assessed using the Swedish version of the 10-item General Self-Efficacy Scale, and sick leave was assessed based on participants' self-reported percentage of sick leave in relation to full-time work. The primary outcome was analyzed according to the intention-to-treat principle using the Mantel-Haenszel chi-square trend test. A total of 654 patients were assessed for eligibility, of whom 59 were included in the final analysis: 29 in the intervention group and 30 in the control group. More participants in the control group (11/30, 36.7%) than in the intervention group (3/29, 10.3%) showed deterioration, resulting in a significant difference in the composite score between the groups at the 6-month follow-up (P=.04), favoring the intervention. This significance also remained in the nonimputed analysis (P=.04). This study suggests that PCC via telephone and an eHealth platform may influence the level of sick leave and self-efficacy among persons with chronic pain. Since the control group deteriorated while the intervention group largely remained unchanged, PCC may play a protective role in supporting persons with chronic pain in returning to work. Further studies are warranted to confirm these findings.

To analyze the incidence of lung cancer associated with social, economic, and environmental indicators. This is an ecological study with 700 new cases of lung cancer, extracted from the IntegradorRHC-INCA database. Average annual incidence rates were calculated, adjusted using the direct method, and subjected to geographically weighted regression analysis. The independent variables were socioeconomic and environmental indicators, including per capita income and primary healthcare coverage. A positive correlation was observed between incidence and per capita income, as well as with primary healthcare coverage. The results point to the need for targeted interventions and the strategic allocation of resources in priority areas, as well as the expansion and strengthening of Primary Health Care for early detection, prevention, and guidance on the risks of developing lung cancer.

The opioid crisis has remained a public health challenge in the US for more than two decades. After increasing from 2002 to 2012, opioid-related hospitalizations decreased from 2016 to 2019, but more recent trends are unknown. We sought to determine trends in incidence and outcomes of US opioid-related hospitalizations in recent years. We conducted a serial cross-sectional study of adult primary and secondary opioid-related hospitalizations, using the 2016-23 National Inpatient Survey and regression models, annual percent change, and z-tests to examine change during the study period. Measures included annual opioid-related hospitalizations, hospital stay outcomes, and sociodemographic characteristics. Among the 1.48 million opioid-related hospitalizations during 2016-23, survey-weighted to 7.42 million, 0.93 million were classified as primary and 6.49 million as secondary opioid-related hospitalizations. Hospitalizations decreased through 2023 for all groups except patients who were Hispanic or Native American, who reported Medicaid as their payer, or who were older than age sixty-five. The greatest decline occurred among people younger than age thirty-five. The proportion of hospitalizations ending in death and self-directed discharge increased by 0.58 percentage points and 2.68 percentage points, respectively. Overall, differential reductions in opioid-related hospitalizations and increasing mortality and self-directed discharge highlight opportunities for interventions.

Toddler's fractures are non-displaced spiral fractures of the lower third of the tibia which are usually sustained during a minor fall. These fractures are surrounded by a thick outer lining of bone (the periosteum), which typically makes them stable. Treatment approaches vary; most clinicians use casts or boots to immobilise the leg, whereas others observe recovery without immobilisation. Both approaches are thought to be safe. Whilst immobilisation protects the leg, it can cause issues with stiffness, recovery and complications. The aim of the ToTs study is to determine whether no-immobilisation is non-inferior to immobilisation in young children with toddler's fractures. This randomised controlled trial aims to recruit 494 participants aged 9 months up to their 4th birthday, who present with clinically suspected or radiologically confirmed toddler's fractures. Most participants are expected to be recruited from emergency departments or fracture clinics. Patients will be randomly allocated 1:1, to either immobilisation or no-immobilisation. The primary outcome is the FLACC (Face, Legs, Activity, Cry, Consolability) behavioural pain assessment completed by parents/guardians at 7 days post randomisation. The primary comparison will assess non-inferiority using a margin of 1 point on the FLACC scale. Secondary outcomes include pain at 3 and 28 days, hospital attendances, need for treatment of pressure ulcers and fracture displacement after randomisation, recovery of mobility, analgesic use, resource use, and satisfaction, collected either by review of medical notes at 28 days, or parent/guardian questionnaires. The cost-effectiveness of the different treatment strategies will also be assessed. Patient and Public Involvement and Engagement informed the study design and will assist with aspects of trial delivery and dissemination. The ToTs trial addresses a lack of high-level evidence regarding the management of toddler's fractures. This will generate evidence to guide clinical practice regarding whether these fractures should be immobilised.

Age-related macular degeneration (AMD) causes progressive central vision loss in older adults. Low-vision rehabilitation can improve functional vision by training the use of a preferred retinal locus, commonly through clinic-based biofeedback training (BFT). However, repeated supervised rehabilitation is burdensome, and functional gains may be difficult to sustain without home practice. Stand-alone virtual reality (VR) may enable home-based, remotely monitored visual stimulation, but feasibility, safety, and usability in older adults with AMD remain insufficiently characterized. This study aimed to evaluate the feasibility and safety of adding home-based VR 3D single-object tracking (3D-SOT-VR) to conventional BFT in older adults with dry AMD in a parallel, randomized, single-blind (to assessors), controlled, formative trial and to generate exploratory functional hypotheses for a future trial. Adults with dry AMD were recruited at the Low Vision Clinic, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada, from September 2021 to October 2023. Participants were randomized to BFT once weekly for 4 weeks (BFT group) or BFT plus home-based 3D-SOT-VR (BFT-VR group) every other day for 4 weeks. Experimental intervention consisted of tracking a single object among distractors moving at different speeds in a 3D virtual space in a VR headset. Primary feasibility and safety outcomes included recruitment, adoption, adherence, compliance, intervention completion, remote data transfer, usability, and VR-induced symptoms and effects. Secondary outcomes included visual acuity, contrast sensitivity, fixation stability, retinal sensitivity, reading speed, and low-vision quality of life. Exploratory outcomes assessed performance at 3D-SOT-VR and usage. Analyses were descriptive and exploratory, with CIs and denominators reported to reflect limited precision and missingness. Fourteen individuals were randomized (BFT, n=6; BFT-VR, n=8), below the planned sample size of 32. Recruitment was not achieved because of COVID-19-related interruptions and reduced onsite access. Eleven individuals were analyzed for the primary outcome (BFT n=6, BFT-VR n=5). Intervention completion was 100% in the BFT arm and 75% in the BFT-VR arm, below the prespecified BFT-VR threshold. Among participants who used VR, adherence to scheduled home sessions was acceptable, completed VR-session files were transmitted without loss, and no participant met the predefined cybersickness stopping rule. One BFT-VR participant discontinued because headset weight caused neck fatigue. Group-level visual outcomes did not provide significant effectiveness. Reading speed showed a clinically meaningful individual-level improvement in the BFT-VR arm and correlated with VR-task performance. The findings were not clearly durable at follow-up. This pilot study provides formative evidence that clinic-based BFT combined with home-based, remotely monitored VR visual stimulation can be implemented safely in older adults with dry AMD, while identifying major contextual feasibility barriers. The intervention is innovative because it extends low-vision rehabilitation into the home using a connected device and objective performance monitoring. Recruitment, retention, missing data handling, and sustainability of functional gains must be addressed before effectiveness testing.

To describe a less invasive laser therapy for retinopathy of prematurity, referred to as ridge-adjacent laser treatment (RALT), and its outcome regarding the need for re-treatment. This was a retrospective observational review of medical records of all infants treated with RALT as a primary intervention for retinopathy of prematurity between June 2016 and June 2021 at a tertiary care center in Sweden. The intervention consisted of RALT with intraoperative wide-field imaging, and most patients also received postoperative dexamethasone eye drops. The primary outcomes measured were the number of laser spots applied, re-treatment rates, and the maximum stage of retinopathy of prematurity observed. Sixty-one eyes of 31 infants were treated with RALT. The median follow-up time was 24 weeks (range: 17 to 45 weeks) after birth. The mean number of laser spots administered was 859 ± 280. Re-treatment was required in 3% of the eyes (6% of the infants). After excluding infants with aggressive retinopathy of prematurity the re-treatment rate for the eyes was 2% (4% of the infants). Seven of the 61 eyes were diagnosed as having aggressive retinopathy of prematurity. In three of these eyes, the retinopathy progressed to a maximum stage greater than 3 following RALT treatment. Treatment of retinopathy of prematurity using the RALT technique, in conjunction with intraoperative wide-field imaging and, in most infants, postoperative dexamethasone eye drops, was associated with a low number of laser spots and a low re-treatment rate. All eyes that did not have aggressive retinopathy of prematurity regressed after the RALT treatment. Further longitudinal studies are required to assess the long-term structural and functional outcomes.

Evidence for non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy for older patients with atrial fibrillation (AF) and drug-eluting stents is lacking. We aimed to evaluate the safety and efficacy of NOAC monotherapy in older AF patients with drug-eluting stents. This is a secondary analysis of the ADAPT AF-DES randomised trial comparing NOAC monotherapy with combination therapy with NOAC plus clopidogrel in patients with AF and drug-eluting stents. Patients were stratified by age (&#x2265;75&#xa0;years and <75&#xa0;years). Apixaban or rivaroxaban was used as the NOAC. The primary endpoint was a net adverse clinical event at 1&#xa0;year after randomisation, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism or major or clinically relevant non-major bleeding defined by the International Society on Thrombosis and Haemostasis criteria. Among 960 patients included in the ADAPT AF-DES trial, 376 (39.2%) patients were aged &#x2265;75&#xa0;years. In patients aged &#x2265;75&#xa0;years, the incidence of the primary endpoint was lower in the NOAC monotherapy group (9.8% vs. 22.3%; adjusted hazard ratio, 0.37; 95% confidence interval, 0.21-0.66; P&#x2009;<&#x2009;.001) than in the combination therapy group. In contrast, the incidences did not differ between treatment strategies in patients aged <75&#xa0;years. The interaction between age groups and strategy groups did not reach statistical significance (P for interaction&#x2009;=&#x2009;.095). The reduction in major or clinically relevant non-major bleeding with NOAC monotherapy was consistent across age groups. In contrast, the benefit of NOAC monotherapy in major adverse cardiac and cerebrovascular events was more pronounced in patients aged &#x2265;75&#xa0;years, with a statistically significant interaction. In this post hoc analysis, NOAC monotherapy was associated with a lower risk of net adverse clinical events, specifically within the older age subgroup. Tailored approach regarding age and individual ischaemic risk may be needed.

Liver cancer is the fourth leading cause of global cancer mortality, with hepatocellular carcinoma (HCC) accounting for most primary liver cancers. The nucleolus, as the primary site of ribosome biogenesis, plays a crucial role in HCC development. Here, we report that the nucleolar protein KRR1 interacting protein (KRI1) is aberrantly overexpressed in HCC tissues and interacts with nucleophosmin 1 (NPM1) via phase separation to maintain nucleolar structure and ribosome biogenesis. Downregulation of KRI1 significantly impairs HCC cell proliferation and increases apoptosis, accompanied by disrupted nucleolar structure and ribosome biogenesis. Moreover, we show that KRI1 phase separation is enhanced by the phosphorylation of three serine residues (S94, S95, and S97) in its N-terminal intrinsically disordered region, and pyruvate kinase M2 (PKM2) is identified as the key kinase. PKM2 inhibitor shikonin markedly attenuates KRI1 phase separation and its interaction with NPM1, disrupts nucleolar structure and ribosome biogenesis, thereby inhibiting HCC progression. This study uncovers the crucial role of KRI1 in HCC progression and provides theoretical and experimental evidence for the development of nucleolar protein-targeted therapeutic strategies for HCC treatment.

Brain microvascular endothelial cells (BMECs) are the main cellular component of the blood-brain barrier (BBB) and play a key role in regulating molecular transport and maintaining central nervous system homeostasis. Reliable in vitro&#xa0;models of brain endothelium are essential for studying BBB physiology and dysfunction in neurological and systemic diseases. A reproducible protocol for the isolation and primary culture of BMECs from neonatal murine cerebral cortex is described. The method includes cortical tissue dissection, mechanical and enzymatic dissociation, removal of myelin debris using a bovine serum albumin (BSA) density gradient, and enrichment of endothelial cells using CD31-based immunoselection. Isolated cells are subsequently cultured on collagen-coated plates and characterized by morphological assessment, immunofluorescence detection of endothelial markers, angiogenic tube formation assays, and transendothelial electrical resistance (TEER) measurements to evaluate barrier properties. This protocol provides a reliable approach for obtaining primary BMEC cultures suitable for investigating BBB biology, endothelial signaling, and neurovascular interactions under physiological and pathological conditions.

New Accreditation Council for Graduate Medical Education and American Board of Family Medicine guidelines encourage training family medicine residents in point-of-care ultrasound (POCUS). Prior studies have focused on the perceived needs of learners but did not assess patient or community need. We performed a triangulated learner- and patient-oriented needs assessment to inform POCUS curriculum development within a family medicine residency. Our learner assessment consisted of a Likert scale survey of the perceived skill and importance of 36 POCUS modalities discussed in the 2016 American Academy of Family Physicians POCUS curriculum guidelines. Our patient-oriented needs assessment was collected through analysis of all family medicine practice (FMP) site imaging orders placed in 2023. The learner survey demonstrated the highest skill gaps in POCUS training to be evaluation for hemothorax and evaluation for pleural effusion. FMP site imaging order analysis demonstrated that hepatobiliary and obstetrics/gynecology concerns were the most frequently answered by POCUS for patients seen at the FMP site. POCUS is an important and underutilized diagnostic tool in family medicine. POCUS curricula in graduate medical education are vital to successful implementation of POCUS in primary care; however, needs assessment techniques used in prior studies differ from the patient and community needs in our study. We recommend the use of both needs assessment strategies for optimal POCUS training outcomes. Further research replicating this modality is necessary to determine the optimal needs assessment approach for POCUS in family medicine.

Short peripheral catheters (SPCs) are the most frequently used vascular access devices in neonatal care. However, prospective data quantifying the procedural burden of SPC use and identifying predictors of complications in term and preterm infants remain limited. In this prospective cohort study, 170 neonates undergoing SPC insertion during the first 7 days of life were included. A total of 354 cannulation procedures were recorded. The primary outcome was the occurrence of at least one SPC-related complication. Procedural burden was assessed using descriptive and exposure-adjusted analyses, and predictors of complications were evaluated using multivariable logistic regression. First-attempt success was achieved in only 30.6% of infants, and the median number of attempts required per patient was 3 (range 1 - 23). At least one complication occurred in 66.5% of neonates. In multivariable analysis , day of life at first cannulation, more than one insertion attempt, and parenteral nutrition were independently associated with complications. SPC use in neonates was associated with substantial procedural burden and frequent complications. Importantly, this burden was not confined to the most immature infants, but was also pronounced in moderate and late preterm neonates. These findings suggest that a routine peripheral-first strategy may not always be appropriate in this group and support earlier consideration of alternative vascular access strategies.

The role of selective non-operative management (SNOM) after gunshot and blast injuries has been increasingly recognized but not explored in animal models. Overall, 24 male pigs were prepared, of which 12 were used to create a gunshot wound model, and the remaining 12 a blast injury model. Animals in each injury model were randomly divided into immediate surgery and SNOM groups using a computer-generated random sequence. Gunshot injury was created by firing a 7 mm, 1.45 g steel ball at the right upper abdomen from 10 cm under 170 bar. Blast injury was created by exposing the right upper abdomen to a high-pressure shock wave from 6 cm under 170-190 bar. In the SNOM group, focused assessment with sonography for trauma (FAST) was performed immediately after modeling and repeated when hemodynamic instability or clinical deterioration was suspected. Conversion to surgery was triggered by persistent heterogeneous echogenicity or hypoechoic fluid on FAST, hemodynamic instability, or progressive clinical deterioration. The primary outcome was the 7-day SNOM outcome. SNOM failure was defined as conversion to surgery or death. After gunshot injury modeling, the 7-day survival rate was 91.67% (11/12). In the immediate surgery group, 2 pigs underwent therapeutic laparotomy, and 4 underwent negative laparotomy. In the SNOM group, 1 pig underwent conversion to surgery, 1 died of hemorrhagic shock on day 1 after modeling, and 4 successfully completed SNOM. After blast injury modeling, the 7-day survival rate was 100% (12/12). In the immediate surgery group, 3 pigs underwent therapeutic laparotomy, and 3 underwent negative laparotomy. In the SNOM group, 2 pigs underwent conversion to surgery, and 4 completed successful SNOM. This work describes the establishment of preliminary injured porcine models, presents representative outcomes of the SNOM and immediate laparotomy strategies, and underscores the need for close monitoring when using the SNOM strategy.

Patellar resurfacing in total knee arthroplasty requires stable cement fixation of the patellar button. Unlike femoral and tibial components, the patellar button is held under manual compression until cement curing, potentially prolonging operative time. Since the patella experiences limited immediate loading after joint closure, a shorter compression time might suffice for primary fixation. This study investigated the effect of reduced manual compression time on cement morphology, micromotion and load-to-shear failure of cemented all-polyethylene patellar buttons. Twelve human patellae from six donors were implanted with cemented all-polyethylene patellar buttons and assigned to either 30 or 600-s compression group. Micro-computed tomography (&#xb5;CT) analysis assessed cement volume, penetration depth, expansion and height. Biomechanical testing included cyclic loading to determine micromotion, followed by shear testing to measure maximum failure force. Statistical comparisons and correlation analyses evaluated group differences and associations between cement morphology and biomechanical parameters. Cement morphology did not differ significantly between groups; volume, penetration depth, expansion and height were comparable. However, micromotion was significantly higher in the 30-s group (0.015&#x2009;&#xb1;&#x2009;0.009&#x2009;mm) compared to the 600-s group (0.006&#x2009;&#xb1;&#x2009;0.003&#x2009;mm, p&#x2009;=&#x2009;0.028). The larger standard deviation in the 30-s group indicated greater variability. Maximum shear force did not differ significantly between groups (2450&#x2009;&#xb1;&#x2009;971 vs. 2383&#x2009;&#xb1;&#x2009;232&#x2009;N, p&#x2009;=&#x2009;0.857). Correlation analyses showed only limited associations between cement morphology and biomechanical outcomes. Reduced compression time did not significantly affect cement morphology or ultimate shear strength of cemented patellar buttons. However, shortened compression led to significantly increased micromotion, indicating impaired early interface stability. These findings suggest that micromotion under cyclic loading may be a more sensitive endpoint than maximum shear force for evaluating patellar button cementing strategies. Maintaining compression until full cement curing may optimize primary fixation stability. Level V, biomechanical study.

Whether severe early motor deficit after deep intracerebral hemorrhage represents a fixed recovery ceiling or a recoverable mixture of structural and reversible mechanisms is unclear. We synthesized time-dependent motor outcomes and corticospinal tract-related predictors after basal ganglia or thalamic hemorrhage. Following PRISMA 2020 and Synthesis Without Meta-analysis guidance, with the protocol prospectively registered on OSF (DOI 10.17605/OSF.IO/JH86X), we searched PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library from inception to April 2026. Adults with spontaneous deep supratentorial intracerebral hemorrhage and any motor outcome measure were eligible. Studies were classified into severe-deficit, broader, and predictor cohorts. The primary synthesis was structured, with a limited aggregate proportion for rehabilitation-discharge walking independence. Risk of bias was assessed with the Quality in Prognosis Studies tool. Of 1,463 records identified, 25 studies were included. Six severe-baseline cohorts demonstrated meaningful six-month motor recovery; gains in severe putaminal hemorrhage appeared concentrated within the first four months. In two broader rehabilitation cohorts, approximately 53% achieved Functional Ambulation Category &#x2265;4 at discharge - a contextual estimate, not a severe-baseline recovery rate. Across fourteen imaging-predictor studies, corticospinal tract integrity, fractional anisotropy, CT-based corticospinal tract lesion load, and posterior-limb internal-capsule involvement were directionally consistent predictors of motor outcome, with supportive multicenter CT-based evidence from a multinational study. Severe early motor deficit does not define an immediate recovery ceiling after basal ganglia or thalamic hemorrhage, but recovery is anatomically constrained by corticospinal tract and posterior-limb internal-capsule involvement. Prognostic counseling should integrate acute imaging-based assessment with the four-month recovery window suggested in severe putaminal hemorrhage.

Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX/mFFX) is the standard adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), offering survival benefits over gemcitabine (GEM). However, the contribution of molecular biomarkers to treatment selection remains unclear. Here, we characterize the molecular landscape of tumors from the PRODIGE-24/CCTG PA6 trial and assess the clinical impact of genomic alterations and molecular subtypes. Tumor DNA sequencing was successfully performed in 317/350 tumors (168 mFFX; 149 GEM), complemented by transcriptomic subtyping using the PurIST classifier. Mutational status of four key PDAC driver genes and 24 homologous recombination repair (HRR)-associated genes was analyzed, alongside single-base substitution (SBS) mutational signatures. Primary and secondary end points were disease-free survival (DFS) and cancer-specific survival (CSS), respectively. In the mFFX group, the PurIST subtype was prognostic, with classical tumors showing superior DFS compared with basal-like tumors (stratified hazard ratio [sHR], 0.48 [95% CI, 0.31 to 0.77]). Among KRAS-mutated patients, mFFX significantly improved DFS compared with GEM (sHR, 0.60 [95% CI, 0.45 to 0.79]; P < .001), while no benefit was observed in KRAS wild-type tumors (interaction test, Pint. = 0.010). HRR and BRCA status were not predictive (Pint. = .568 and Pint. = .785, respectively). The benefit of mFFX was consistent across SBS-positive and SBS-negative subgroups. Overall, these results do not support a change in current adjuvant treatment strategies. mFFX remains the standard adjuvant regimen in PDAC, and the observed lack of benefit in KRAS wild-type tumors should be considered hypothesis-generating and warrants further investigation.