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Application of Three-Dimensionally Printed Surgical Guides in Precise Sacral Tumor Excision and Defect Reconstruction.

OBJECTIVE: Precise resection of sacral tumors remains technically demanding due to their deep anatomical location and close proximity to critical neurovascular structures. Conventional freehand techniques often result in suboptimal resection margins, excessive blood loss, and compromised lumbopelvic stability. This study evaluated whether patient-specific three-dimensional (3D)-printed guiding templates improve surgical accuracy and perioperative outcomes in sacral tumor resection and reconstruction. METHODS: Nineteen patients undergoing en bloc sacral tumor resection (S1-S3 involvement) with spinopelvic reconstruction (2006-2020) were retrospectively analyzed. Patients were divided into a 3D-printing group (n&#x2009;=&#x2009;10) and a conventional freehand group (n&#x2009;=&#x2009;9). In the 3D-printing group, computer-aided design and 3D-printed templates were used for osteotomy, screw placement, and defect reconstruction. Perioperative metrics, surgical accuracy, and complications were compared between groups using Welch's t-test and the Hodges-Lehmann method; oncologic events during follow-up were recorded descriptively. RESULTS: The 3D-printing group demonstrated significantly shorter operative time (456.5&#x2009;&#xb1;&#x2009;62.36 vs. 574.44&#x2009;&#xb1;&#x2009;114.58&#x2009;min, p&#x2009;=&#x2009;0.012), reduced blood loss (4081.40&#x2009;&#xb1;&#x2009;838.99 vs. 5090.0&#x2009;&#xb1;&#x2009;1059.67&#x2009;mL, p&#x2009;=&#x2009;0.034), and fewer fluoroscopic exposures (4.2&#x2009;&#xb1;&#x2009;0.79 vs. 10.0&#x2009;&#xb1;&#x2009;1.58, p&#x2009;<&#x2009;0.001) compared with the conventional group. Osteotomy accuracy was also superior in the 3D-printing group, with significantly lower angular deviation (3.33&#xb0;&#x2009;&#xb1;&#x2009;0.45&#xb0; vs. 6.79&#xb0;&#x2009;&#xb1;&#x2009;2.16&#xb0;, p&#x2009;=&#x2009;0.0012). Postoperative complication rates were comparable (30% vs. 44.4%, p&#x2009;=&#x2009;0.649), but hospital stay was significantly shorter in the 3D-printing group (10.7&#x2009;&#xb1;&#x2009;2.71 vs. 18.11&#x2009;&#xb1;&#x2009;4.01&#x2009;days, p&#x2009;<&#x2009;0.001). CONCLUSION: Patient-specific 3D-printed guiding templates enhance precision in sacral tumor excision and reconstruction, improving surgical efficiency and perioperative safety. This computer-assisted, template-guided approach represents a valuable advancement for complex sacral oncologic surgery.

Humans

Healthcare Access and Safety Training Gaps Among H-2&#xa0;A Visa Agricultural Workers in Georgia.

The H-2&#xa0;A Temporary Agricultural Workers Program, which supplies seasonal labor essential to U.S. food security, has grown over 230% in the past decade but is excluded from the National Agricultural Workers Survey. Although safety training is federally mandated and H-2&#xa0;A workers are eligible for Affordable Care Act (ACA) marketplace coverage, compliance and healthcare access among these workers remain poorly documented. The aim of this pilot study was to assess workplace safety training, heat acclimatization practices, health insurance awareness and enrollment, and healthcare utilization among H-2&#xa0;A workers in Georgia. In summer 2024, bilingual research assistants orally administered a cross-sectional Spanish-language survey to 51&#xa0;H-2&#xa0;A workers at a South Georgia laundromat, in partnership with the Latino Community Fund Georgia. The survey assessed demographics, occupational characteristics, safety training, heat acclimatization, health insurance awareness and enrollment, and healthcare utilization. Findings are self-reported. Among participants, 41% reported not receiving federally mandated pesticide safety training, and 59% received heat illness prevention training. Heat acclimatization was inadequate for 53% (29% received none). Additionally, 53% did not know the nearest hospital, 43% reported having health insurance, and 25% were unsure of their health insurance status. Overall, 71% had never visited a doctor's office, and of 22 insured workers, only 1 (2%) had used benefits this season. Substantial gaps in workplace safety training, heat acclimatization, and healthcare access were observed in this pilot study, consistent with prior evidence of persistent disparities in this population. Community-based outreach, bilingual health navigation, and market-based labor accountability models warrant further investigation to improve protections for H-2&#xa0;A workers.

Agricultural workers

Efficacy and Safety of Anti-Obesity Medications for Weight Loss Maintenance in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

AIMS: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of anti-obesity medications (AOMs) for long-term weight maintenance following initial weight loss in adults with overweight or obesity. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library from inception to 31 October 2025. Eligible studies were randomised controlled trials (RCTs) comparing AOMs with placebo during the weight-maintenance phase in adults with overweight or obesity after initial weight loss achieved through lifestyle, dietary, surgical or pharmacological interventions. Outcomes included anthropometric indices, cardiometabolic measures, safety endpoints, quality of life and neuropsychiatric adverse events. Weighted mean differences (WMDs) and odds ratios (ORs), each with 95% confidence intervals (CIs), were pooled for continuous and categorical outcomes, respectively, using fixed-effect or random-effects models as appropriate. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE framework. The protocol was registered with PROSPERO (CRD420261293040). RESULTS: A total of 12 RCTs comprising 4915 participants met the inclusion criteria. Compared with placebo, AOM therapy during the weight-maintenance phase was associated with prevention of weight regain and additional improvements in anthropometric and cardiometabolic outcomes. AOMs led to further reductions in body weight (BW, WMD: -8.68&#x2009;kg, 95% CI: -13.25 to -4.11), waist circumference (WC, WMD: -7.16&#x2009;cm, 95% CI: -10.34 to -3.98) and body mass index (BMI, WMD: -3.58&#x2009;kg/m2, 95% CI: -5.69 to -1.46). Additional benefits were observed for triglycerides, total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure and diastolic blood pressure. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Neuropsychiatric adverse events were generally comparable between groups, and available quality-of-life measures favoured AOM treatment. CONCLUSIONS: AOM therapy during the weight-maintenance phase can help prevent weight regain, provide further reductions in body weight and improve cardiometabolic risk factors in adults with overweight or obesity. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Further long-term trials are needed to clarify optimal treatment strategies and safety.

Humans

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate &#x2265;&#x2009;90; 60-<&#x2009;90; 30-<&#x2009;60; <&#x2009;30&#x2009;mL/min/1.73&#x2009;m2) and liver (total bilirubin &#x2264;&#x2009;21&#x2009;&#x3bc;mol/L or aspartate aminotransferase [AST] &#x2264;&#x2009;31/&#x2264;&#x2009;37 [female/male] U/L; total bilirubin >&#x2009;21&#x2009;&#x3bc;mol/L or AST >&#x2009;31/>&#x2009;37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p&#x2009;>&#x2009;0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c <&#x2009;7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p&#x2009;<&#x2009;0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p&#x2009;<&#x2009;0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans

Exercise Snacks Are Feasible to Perform in the Real World and Improve Physical Capacity for Adults Living With Non-Insulin Treated Type 2 Diabetes: A Randomised Trial.

AIMS: To investigate the feasibility and preliminary efficacy of a 12-week remotely-delivered exercise snacks (ES) intervention in adults with type 2 diabetes. MATERIAL AND METHODS: Insufficiently active adults with type 2 diabetes (N&#x2009;=&#x2009;69; 46 females; mean age&#x2009;&#xb1;&#x2009;SD: 58&#x2009;&#xb1;&#x2009;11&#x2009;years) were randomised to an ES or mobility/stretching comparator group (CON), which involved 4&#x2009;&#xd7;&#x2009;1-min bouts of either vigorous or low intensity exercise, respectively, on &#x2265;&#x2009;5&#x2009;days/week. The primary outcome was feasibility based on adherence. Secondary outcomes included exercise enjoyment (1-7 scale), rating of perceived exertion (RPE; 0-10 scale), heart rate (HR), haemoglobin A1c (HbA1c), blood biomarkers of cardiometabolic health, 30-s sit-to-stand capacity, grip strength, estimated maximal oxygen uptake, and anthropometrics. RESULTS: Weekly adherence (estimated marginal mean [95% confidence interval]: 18 bouts [16-21] for both groups; p&#x2009;=&#x2009;0.99) and total enjoyment (ES: 4.5 [4.1-4.8] vs. CON: 4.3 [4.0-4.7]; p&#x2009;=&#x2009;0.64) were high and not different between groups. Despite higher RPE (5.7 [5.4-6.1]) and peak HR (73 [70-77] % of age-predicted HR maximum) in ES versus CON (2.0 [1.7-2.4] and 61 [58-64] % of age-predicted HR maximum, respectively) (all p&#x2009;<&#x2009;0.001), there were no between-group differences in the change in any secondary outcome (all p&#x2009;>&#x2009;0.05) except for greater sit-to-stand capacity in ES after training (between-group effect estimate [95% confidence interval]: 1.9 repetitions [0.3-3.4]; p&#x2009;=&#x2009;0.02). CONCLUSIONS: Exercise snacks were feasible to perform in the real world and improved sit-to-stand capacity to a greater extent than CON in adults living with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06407245.

Aged

Enrichment of Lysobacter in a long-term organically managed agricultural field with low soilborne disease incidence.

Disease-suppressive soils, in which soilborne pathogens are naturally suppressed, offer a promising model for sustainable crop protection, particularly in organic farming systems where chemical disease control options are limited. Although disease suppression in these soils is considered to rely on biological control, the underlying mechanisms remain poorly understood. In this study, we investigated soil from a long-term organically managed field in Shiga Prefecture, Japan, where soilborne disease incidence has remained consistently low, to identify bacterial community features potentially associated with this field. The 16S rRNA gene amplicon sequencing indicated that this soil harbored a bacterial community distinct from those of nearby agricultural soils. Following the application of organic compounds, the genus Lysobacter, a taxon with known antagonistic activity against plant pathogens, was markedly enriched in response to proteinaceous organic inputs. This enrichment was consistent across sampling times and specific to certain proteinaceous organic inputs, whereas minimal effects were observed on chitin, N-acetyl-d-glucosamine, or cysteine. Broader soil surveys indicated that Lysobacter enrichment was not strictly associated with whether soils had been managed under organic or conventional farming practices. Stepwise multiple regression analysis identified 10 co-occurring bacterial genera that were strongly associated with Lysobacter abundance. These findings highlight condition-dependent Lysobacter enrichment as a characteristic microbial response to proteinaceous organic amendments in this low-disease-incidence field and provide microbial insights that may inform microbiome-based strategies for sustainable soil management.

Lysobacter

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5&#xa0;years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (&#x2265;&#x2009;90, 60-89, 30-59&#x2009;mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of &#x2265;&#x2009;125&#x2009;pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values <&#x2009;0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2&#x2009;pg/mL, p&#x2009;<&#x2009;0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r&#x2009;=&#x2009;0.31, p&#x2009;<&#x2009;0.001). However, no significant association was found between NT-Pro BNP and FMD (p&#x2009;=&#x2009;0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p&#x2009;<&#x2009;0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p&#x2009;=&#x2009;0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p&#x2009;=&#x2009;0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p <&#x2009;0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT&#x2010;Pro BNP

Multi-omics reveal microbial functional traits and antifungal metabolites associated with lower Pseudogymnoascus destructans loads in bat cave soils.

White-nose syndrome, caused by Pseudogymnoascus destructans (Pd), is a major fungal disease threatening hibernating bats. Cave soils can serve as environmental reservoirs for Pd, yet the microbial and biochemical mechanisms underlying naturally low Pd burdens in some cave environments remain poorly understood. Here, we integrated soil microbiome profiling, metagenomics, metabolomics, multi-omics network analysis, and in vitro validation to investigate the ecological and functional basis of differential Pd loads in hibernating bat caves in Northeast China. The three caves shared cold, humid, and weakly acidic microenvironments, but differed significantly in electrical conductivity, soil water content, nutrient availability, and extracellular enzyme activities. Soil microbial communities showed significant inter-cave variation in composition, diversity, and niche breadth, with stochastic processes contributing substantially to community assembly. Environmental variables, particularly pH and Pd load, were important predictors of microbial community structure. Functional analyses revealed that the low-Pd Gezi Cave was enriched in genes associated with organic carbon degradation, nitrogen input and retention, and secondary metabolism. Metabolomic profiling further identified cave-specific metabolite signatures, among which Biochanin A, 4-Hydroxybenzaldehyde, Vanillin, and Arachidonic acid were negatively correlated with Pd loads. Integrated pathway and network analyses showed that differential genes and metabolites jointly mapped to secondary metabolite biosynthesis, aminobenzoate degradation, and flavonoid degradation pathways, forming a microbe-metabolite-functional gene coupling network involving key taxa such as Rhodococcus, Pseudorhodoplanes, and Rhodoplanes. In vitro assays confirmed that 4-Hydroxybenzaldehyde, Coumarin, and Vanillin inhibited Pd growth. Structural equation modelling further indicated that environmental heterogeneity was associated with variation in Pd loads through microbial functional attributes and metabolite profiles. These findings suggest that naturally low-Pd cave soils are associated with coordinated environmental filtering, microbial functional specialization, and antifungal metabolite production, providing mechanistic insight into microbial and biochemical constraints on Pd persistence in cave reservoirs.

Animals

Getting to the Core of the Matter-Assessing the Role of Replication in Metabarcoding-Based sedaDNA.

Replication is central to most experimental and sampling designs, increasing inferential power and capturing fine-scale data heterogeneity. However, its importance remains poorly evaluated in some ecological and evolutionary settings. This is the case of metabarcoding studies using DNA recovered from sedimentary archives, in which biological signals integrate ecological information through depositional and burial processes, yet are commonly inferred from a single sediment core per site. Here, we evaluated the effect of different types of replication using sedimentary DNA metabarcoding data from two genetic markers (mitochondrial COI and nuclear 18S) using a nested sampling design. The design included three intertidal sites, three spatially separated sediment cores per site (biological replicates), two sediment horizons per core, and eight PCR (technical) replicates per sediment sample. Variance partitioning showed that site identity and sediment age group together explained >&#x2009;70% of the variation in beta diversity, indicating that among-site spatial and stratigraphic differences were the dominant drivers of community composition. PERMANOVA likewise identified non-significant effects of biological replication. Among PCR replicates from the same sediment sample, richness varied substantially, whereas Shannon diversity was more consistent. Despite this variability, differences in community composition among technical replicates remained smaller than those associated with biological replication or site identity, indicating a limited influence on broader ecological patterns. Community composition was highly similar among replicate cores within sites, consistent with stratigraphic coherence. These results indicate limited within-site heterogeneity and suggest that, under stratigraphically coherent conditions, increasing biological replication may provide little additional information, whereas enhancing technical replication and stratigraphic resolution can improve ecological inference from sedimentary DNA metabarcoding datasets.

DNA Barcoding, Taxonomic

Postoperative Curvature Loss in Three-Level Anterior Cervical Discectomy and Fusion With Zero-Profile Device.

PURPOSE: Cervical curvature loss is a frequent complication following 3-level anterior cervical discectomy and fusion (ACDF) using a Zero-Profile device. Consequently, the capacity of this device to maintain cervical sagittal alignment in 3-level ACDF remains highly controversial. This study aimed to identify potential predictors for postoperative curvature loss (PCL) and evaluate its impact on clinical outcomes. METHODS: A total of 113 patients who underwent ACDF for 3-level cervical degenerative disc disease (CDDD) between January 2021 and December 2023 were retrospectively reviewed. Demographic data, radiological parameters, and clinical outcomes were analyzed. Radiographic measures included cervical curvature, T1 slope, C2-7 sagittal vertical axis, and titanium plate and endplate (TPE) distance. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores. Statistical analyses were performed using paired and independent t-tests, as well as Pearson correlation coefficients. RESULTS: The average curvature loss was 6.82&#xb0; from 1&#x2009;week postoperatively to the final follow-up (p&#x2009;<&#x2009;0.001). However, the final curvature (11.65&#xb0;) was maintained, representing a 4.33&#xb0; improvement compared to preoperative values. Significant correlations were observed between PCL and preoperative curvature (r&#x2009;=&#x2009;-0.368, p&#x2009;=&#x2009;0.013), preoperative T1 slope (r&#x2009;=&#x2009;-0.546, p&#x2009;<&#x2009;0.001), &#x2206;T1 slope (r&#x2009;=&#x2009;0.443, p&#x2009;=&#x2009;0.002), and &#x2206;TPE distance (r&#x2009;=&#x2009;0.417, p&#x2009;=&#x2009;0.004). PCL did not correlate with Japanese Orthopaedic Association (JOA) scores or arm VAS scores at the final follow-up. Nevertheless, patients with a PCL&#x2009;&#x2265;&#x2009;6&#xb0; exhibited significantly higher neck VAS (p&#x2009;=&#x2009;0.028) and NDI scores (p&#x2009;=&#x2009;0.041). CONCLUSION: Although contiguous 3-level ACDF with a Zero-Profile device may result in PCL, it preserves an improved cervical lordosis compared to the preoperative baseline. Low preoperative curvature and a low preoperative T1 slope are potentially predictive factors for PCL. Postoperative changes in TPE distance and T1 slope are significantly associated with PCL, suggesting a potential biomechanical link that requires direct validation. Furthermore, PCL may lead to higher neck VAS and NDI scores. Consequently, the Zero-Profile device may require careful consideration in 3-level CDDD patients presenting with low preoperative curvature and a low T1 slope. Importantly, the 6&#xb0; PCL threshold identified is preliminary and requires prospective validation before clinical application.

Humans

"It was good because they have a relationship with us": A qualitative study on low-threshold buprenorphine treatment at syringe services programs.

INTRODUCTION: Syringe service programs (SSPs) reach people who inject drugs with opioid use disorder (OUD) and are novel "low-threshold" venues to initiate buprenorphine treatment. The study investigated patients' experiences with SSP-initiated buprenorphine treatment, which could aid in improving buprenorphine treatment delivery at SSPs. METHODS: The study included 12 participants who completed qualitative exit interviews after a randomized controlled trial of buprenorphine treatment at SSPs. In the parent study, participants received buprenorphine treatment through an onsite model at an SSP or enhanced referral to a community health center based on the randomization sequence. Most participants started taking buprenorphine at home. Exit interviews included participants from both study arms, and the semi-structured interview guide focused on their experiences with clinicians, experiences initiating buprenorphine, prior experiences with OUD treatment, and perceptions about continuing buprenorphine treatment. Four researchers iteratively read, coded, and discussed each transcript, then they derived recurring themes using thematic analysis. RESULTS: Participants were mostly male, middle-aged, and 50% identified as Latino. Four main themes related to buprenorphine treatment initiation: 1) Onsite treatment facilitated buprenorphine prescription, but some participants also expressed a need for additional support; 2) Precipitated withdrawal complicated participants' buprenorphine initiation in both arms; 3) Participants largely experienced the SSPs as affirming and welcoming; and 4) Developing strong relationships with healthcare providers was critical to successful buprenorphine treatment initiation. CONCLUSIONS: The SSP-based model provided rapid access to buprenorphine prescriptions, but precipitated withdrawal was a common complication. Some participants desired additional support and guidance when they started taking buprenorphine at home. The findings point to a "low-threshold, high-touch" approach where participants receive expedited access to buprenorphine providers at SSPs but also additional support throughout the initiation process to avoid and/or manage precipitated withdrawal. Despite some challenges, SSP-based buprenorphine treatment was highly valued by study participants.

Humans

Clinical Efficacy and Learning Curve of Far-Lateral Approach (FLA) in Uni-Portal Non-Coaxial Spinal Endoscopic Surgery (UNSES) in the Treatment of Lumbar Degenerative Diseases: A Prospective Study.

BACKGROUND: Uniportal non-coaxial spinal endoscopic surgery (UNSES) via far-lateral approach (FLA) is an innovative minimally invasive procedure for lumbar degenerative diseases, particularly far-lateral disc herniation and foraminal stenosis. However, complex lateral lumbar anatomy and strict endoscope-instrument coordination create a distinct learning curve that may compromise early surgical efficiency and safety. This study aimed to evaluate the efficacy and safety, quantify the learning curve, and to provide clinical guidance for the standardized promotion and application of this technology. METHODS: A total of 40 consecutive patients with lumbar degenerative diseases who underwent UNSES via FLA by a single surgeon between January 2025 and December 2025 were included. All data were analyzed using SPSS 26.0 statistical software (IBM, USA). Primary outcomes included operation time, blood loss, fluoroscopy frequency, and intraoperative complication rate. Secondary outcomes were VAS, ODI, and modified Macnab criteria at 1, 3, and 6&#x2009;months postoperatively. The learning curve and the inflection point of the learning curve was determined using cumulative sum (CUSUM) analysis. The differences in clinical indicators between early and proficient stage were compared. RESULT: Operation time, blood loss, and fluoroscopy times decreased significantly with case accumulation (p&#x2009;<&#x2009;0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3&#x2009;&#xb1;&#x2009;8.6) min, much shorter than the early phase (89.5&#x2009;&#xb1;&#x2009;10.3) min (p&#x2009;<&#x2009;0.001). Before the 16th case, the curve was in an upward trend; after the 16th case, the curve tended to be flat, indicating the proficiency stage. Postoperative VAS and ODI improved significantly than those before surgery at each follow-up time (p&#x2009;<&#x2009;0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p&#x2009;>&#x2009;0.05). The total complication rate was 12.5% (5/40), were cured by conservative treatment. The total excellent-good rate was 90.0% (36/40). L5/S1 and Bertolotti's syndrome were independent factors affecting the learning curve. CONCLUSION: UNSES via FLA is a safe and effective minimally invasive technique for treating complex lumbar degenerative diseases. It has a certain learning curve, and the inflection point is about the 16th case. After mastering the key techniques such as anatomical positioning, endoscopic manipulation and hemostasis, the surgeon can gradually reach the proficiency stage, with significantly improved surgical efficiency and clinical efficacy, and controllable complications. This study provides a theoretical basis for the clinical training and technology promotion of UNSES via FLA.

Humans

A Web-Based, Pedometer-Mediated Intervention Increases Amount and Intensity of Physical Activity in COPD: A Randomized Controlled Trial.

INTRODUCTION: Ground-based walking training is an aerobic exercise used in supervised pulmonary rehabilitation (PR). Physical activity (PA) interventions typically promote step counts, but it is unclear whether community-based walking intensity can be targeted as aerobic exercise. This randomized controlled trial evaluated a web-based, pedometer-mediated PA intervention designed to increase walking amount and intensity. MATERIAL AND METHODS: Participants with COPD who had never enrolled in PR were randomized 1:1 to control or intervention. The intervention included individualized step-count goals, iterative feedback, educational content, and an online community forum. The Fitbit Inspire Heart Rate objectively monitored daily step counts. Participants were instructed to achieve step-count goals with as many steps of moderate-intensity as possible guided by a modified Borg rating of 4-5 for dyspnea. The primary outcome was change in PA measured as average daily step count at 12&#xa0;weeks. Aerobic intensity was assessed by the Rapid Assessment of PA Questionnaire which uses self-reported moderate or vigorous PA to categorize responders as underactive or active. Linear mixed-effects models (PROC MIXED, SAS v9.4), adjusting for group, time, group*time, FEV1%predicted, enrollment season, and study modality (eg, in-person, virtual, hybrid), assessed between-group change. RESULTS: Participants (57 intervention, 52 control) were 97% male, mean age 73&#xb1;7 years, and baseline FEV1 73&#xb1;23% predicted. Baseline daily steps were 4,222&#xb1;1,929 (intervention) and 4,851&#xb1;2,637 (control). Intervention participants increased average daily steps by 1,410 steps/day more than controls (p=0.005). The intervention group showed greater transitions from underactive to active intensity (between-group: p=0.025), with 20 (41%) moving to active status (within-group: p=0.001). CONCLUSION: Technology-mediated community-based walking increased PA amount and intensity. These findings support further evaluation of this intervention as a potential option for ground-based walking training with objective measurement of exercise intensity.

Humans

Solutions for engaging priority populations in HIV cure research: a hybrid Delphi consensus-building process.

BACKGROUND: To achieve consensus on barriers and strategies to improve the engagement of three priority populations - Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research. METHODS: We assembled a panel of 54 experts assigned to six groups in a hybrid Delphi process: (1) HIV community members, (2) biomedical researchers, (3) medical providers, (4) funders and private industry members, (5) bioethicists and regulators, and (6) social scientists. Over 18 months, we conducted four iterative survey rounds and three group discussions to identify barriers and strategies to arrive at a consensus on how to engage these priority populations in HIV cure research. RESULTS: For Black and Latino/a/x populations, the panellists identified inadequate outreach and a lack of accessible educational information as primary barriers and emphasised community-driven engagement and partnerships with trusted leaders as key strategies. For cisgender women, logistical hurdles, caregiving responsibilities and time constraints were identified as major barriers, with flexible trial designs and equitable compensation proposed as solutions. For transgender women, the lack of transgender-focused research design, including misrepresentation and exclusion, was identified as a key barrier, while centring transgender-specific needs in study design achieved consensus as the most effective strategy. CONCLUSION: Among all four priority populations, investment in outreach, engagement along the research process, better integration of health needs with research, and enhanced incentives are not novel ideas, but remain obviously ignored in a way that has led to underrepresentation of people in HIV cure research, who carry the greatest burden of HIV in the U.S. SUMMARY: This paper uses a hybrid Delphi process to identify and reach consensus on key barriers and strategies to engage underrepresented groups: Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research across the United States.

Humans

Family-Wise Error Rate Control in Clinical Trials With Overlapping Populations.

We consider clinical trials with multiple, overlapping patient populations that test multiple treatment policies specifically tailored to these populations. Such designs may lead to multiplicity issues, as false statements will affect several populations. For type I error control, often the family-wise error rate (FWER) is controlled, which is the probability to reject at least one true null hypothesis. If the joint distribution of the test statistics is known, the FWER level can be exhausted by determining critical values or adjusted-levels. The adjustment is typically done under the common ANOVA assumptions. However, the performed tests are then only valid under the rather strong assumption of homogeneous null effects, that is, when the null hypothesis applies to all subpopulations and their intersections. We show that under cancelling null effects, when heterogeneous effects cancel out in some or all subpopulations, this procedure does not provide FWER control. We also suggest different alternatives and compare them in terms of FWER control and their power.

Humans

Communication crossroads: Exploring generational dynamics in nursing from the bedside to the boardroom.

Nurses have up to four times more patient contact than physicians, positioning them as central drivers of communication in health care. Effective communication directly influences patient outcomes, teamwork, staff engagement, and the overall care experience. Today's nurses operate within a highly diverse environment that includes four generations in the workforce and up to eight generations of patients, each with distinct values, expectations, and communication preferences. This article examines how generational differences shape communication across three key relational domains: peer-to-peer, nurse-to-patient, and nurse-to-leader interactions, and offers insights to strengthen collaboration, engagement, and quality of care.

Humans

Patient experiences of diagnostic uncertainty in musculoskeletal care: a systematic review of qualitative studies.

BACKGROUND: Diagnosis plays a central role in musculoskeletal care. However, establishing a clear diagnosis is often challenging, and diagnostic uncertainty is common. OBJECTIVES: To explore patient experiences of diagnostic uncertainty in musculoskeletal care. METHODS: Five databases (CINAHL, Embase, MEDLINE, AMED, Web of Science) were searched from inception to October 2025. Qualitative studies involving semi-structured interviews with adults receiving care for MSK conditions were included. Methodological quality was appraised using the Joanna Briggs Institute Qualitative Checklist. Data were synthesised using thematic synthesis, and confidence in findings was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research approach (GRADE-CERQual). RESULTS: Twenty-six studies involving 462 participants were included. Critical appraisal identified 23 studies with varying methodological limitations; all studies were included in the synthesis. Nine descriptive themes were synthesised into three analytical themes: (1) patient expectations and perceived meanings of a diagnosis and interpretations of diagnostic uncertainty; (2) the multi-dimensional experience of diagnostic uncertainty; and (3) the role of contextual factors, particularly communication and the therapeutic relationship, in shaping experiences of diagnostic uncertainty. Using GRADE-CERQual, confidence in these themes was rated as low, moderate and very low, respectively. CONCLUSION: Diagnostic uncertainty is a subjective and multi-dimensional experience shaped in part by patients' expectations and the meanings attributed to diagnosis. Its impact spans predominantly cognitive and affective domains and may influence clinical presentation. Patient-centred communication and strong therapeutic relationships may support patients in navigating diagnostic uncertainty in musculoskeletal care.

Adult