Search Results (654)

Introduction: Rapid technological development requires continuous learning and adaptation, yet many older adults (OAs) face difficulties using digital technologies. The AGAPE project (Active aGeing And Personalised service Ecosystem) aimed to promote active and healthy ageing (AHA) among adults aged 65+ by supporting independent functioning reducing caregiver burden, and improving eHealth literacy through personalized, user-friendly digital services co-created and tested in Italy, Portugal, and Romania. Objective: AGAPE pilot phase evaluated the effectiveness and usability of innovation adoption strategies designed to improve technology acceptance, digital literacy, and behavioural change among older adults and caregivers. This study examined participants’ perceptions of digital technologies and self-reported digital efficacy during a multicomponent intervention combining repeated technology use, personalized coaching, digital literacy and health education, technical assistance, and support from informal and formal caregivers. Material and Methods: The multiple-sites uncontrolled pilot study combined home-based use of the AGAPE digital technologies with long-term combined personalized support. Data were collected at baseline (T0), intermediate (T1), and final (T2) assessments using the System Usability Scale (SUS), technostress questionnaire, digital adoption questionnaire (TAM-derived), EQ-5D-5L, CarerQoL-7D, and the UCLA Loneliness Scale, complemented by participant feedback, technology usage, and activity data. Results: The study included 217 participants, of whom 146 were OAs. Over the course of the intervention, participants showed reductions in technostress and improvements in perceived digital efficacy, although the magnitude and direction of change varied across pilot sites. The findings also indicated that contextual and social factors contributed to technology adoption and engagement. Conclusions: Participation in the multicomponent AGAPE intervention was associated with positive longitudinal changes in technology-related perceptions, technostress, and digital self-efficacy. The findings support the feasibility and potential of combining digital technologies with personalized coaching and broader interpersonal support to facilitate technology adoption among older adults. However, given the uncontrolled study design and the integrated nature of the intervention, the observed changes cannot be attributed independently to coaching or to any single intervention component. Full article

Objective: The objective of this study was to assess the economic family spillover effects of childhood congenital cytomegalovirus (cCMV) in the US. Methods: This cross-sectional, Web-based study collected economic and health-state utility data between August 2024 and April 2025 using three surveys targeting caregivers of children with cCMV, children with cCMV, and their siblings. Results: Respondents included 227 caregivers, 211 children with cCMV, and 173 siblings. A high economic burden on families of children with cCMV was reported, including total mean annual costs (out-of-pocket medical and personal care expenses and work- or productivity-related costs) of $83,140 and lifetime out-of-pocket home adaptation/specialized schooling costs of $4713. The mean caregiver EQ-5D-5L utility score was 0.86, which is comparable to US general-population norms. Mean Health Utilities Indexes Mark 2 and 3 scores varied within the ranges of 0.38–0.83 and 0.03–0.73, respectively, among children with cCMV. Adult siblings reported a mean EQ-5D-5L utility of 0.90. Siblings aged 4–7 and 8–17 years reported mean EQ-5D-Y-3L utilities of 0.90 and 0.92, respectively. Conclusions: This is the first study to report the family spillover effects of caring for children with cCMV in the US. The results confirm a considerable, multifaceted burden experienced by children with cCMV and their families, spanning health-state utility and economic strains. Full article

Background and Clinical Significance: Diabetic ketoacidosis (DKA) is a common presentation of new-onset type 1 diabetes mellitus in children; however, severe DKA complicated by acute pancreatitis, dialysis-requiring acute kidney injury (AKI), severe hypertension, and neurological involvement is uncommon. Early recognition of these complications is essential because they may substantially increase morbidity and complicate standard DKA management; Case Presentation: An 11-year-old Saudi girl with morbid obesity (BMI 43 kg/m²), previously in good health, was brought to the emergency department after being found semi-conscious. She had experienced intermittent abdominal pain for five weeks and vomiting for four days. On presentation, she was critically ill, dehydrated, and confused (Glasgow Coma Scale 11/15) and exhibited Kussmaul breathing and abdominal tenderness. Laboratory investigations confirmed severe new-onset DKA, with a blood glucose level of 684 mg/dL, pH < 7.0, HbA1c 12.2% and an anion gap > 37 mEq/L. Despite standard DKA management, metabolic acidosis persisted and renal function progressively deteriorated, accompanied by oliguria and severe hypertension reaching 200 mmHg. By day 4, the patient developed anuria and marked creatinine elevation to 560 µmol/L. Brain magnetic resonance imaging demonstrated cerebral microhemorrhages in the setting of multifactorial encephalopathy. Continuous kidney replacement therapy was initiated for KDIGO stage 3 AKI with refractory metabolic acidosis. Autoimmune testing supported the diagnosis of type 1 diabetes mellitus, while renal biopsy demonstrated acute tubular injury; Conclusions: This case highlights a rare, severe multisystem presentation of pediatric DKA. Close monitoring for renal, neurological, pancreatic, and hypertensive complications is crucial, particularly when the clinical course does not improve as expected with standard therapy. Full article

Background: Subjective cognitive complaints (SCCs) are common in middle-aged and older adults and may reflect early cognitive changes, alongside alterations in stress, mood, sleep, and quality of life. N-PEP-12 is a peptide-based nutritional supplement with potential neuroprotective effects, but evidence of its benefits in healthy adults with SCCs remains limited. Objective: To evaluate the effects of N-PEP-12 supplementation on attention, cognitive function, and mental wellbeing in healthy middle-aged and older adults with SCCs. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 276 participants aged 50–75 years with SCCs and no clinically significant cognitive impairment were randomized to placebo, N-PEP-12 45 mg, or N-PEP-12 90 mg. Assessments were performed at baseline and after 30, 90, and 180 days. Primary outcomes included Test of Attentional Performance measures. Secondary outcomes included WAIS-IV Digit Span Forward and Backward, perceived stress, mood, sleep quality, and EQ-5D-5L visual analog scale. Results: Across the three primary attention outcomes analyzed jointly in a multivariate repeated-measures model, there was a significant group-by-visit interaction (p = 0.003) and a significant effect of visit (p < 0.001), without a significant main effect of treatment arm (p = 0.133), indicating a time-dependent treatment effect. This result was obtained in a sensitivity analysis population in which missing values were imputed under assumptions least favorable to the active arms. In exploratory endpoint-specific comparisons at 90 days, both N-PEP-12 groups showed greater improvements than placebo in alertness, attention omissions and memory omissions, and Digit Span Forward and Backward scores also improved. In a subsequent uncontrolled extension phase, in which all participants received active treatment, participants initially assigned to placebo showed comparable improvements after switching to N-PEP-12 90 mg. These observations are exploratory. Adverse events were infrequent and similarly distributed across groups. Conclusions: N-PEP-12 supplementation was associated with improvements in attention, working memory, and mental wellbeing in healthy middle-aged and older adults with subjective cognitive complaints. These findings support further investigation of N-PEP-12 as a nutritional intervention for early subjective cognitive changes associated with aging. Full article

Background/Objectives: Vonoprazan is a potassium-competitive acid blocker with potential for the treatment of equine gastric ulcer syndrome. Vonoprazan metabolic pathways in horses have not been characterized. This study aimed to identify vonoprazan metabolites following oral administration and to determine the metabolic enzymes responsible for their metabolism using in vitro models. Methods: Six healthy adult Thoroughbred horses received vonoprazan (0.5 and 1 mg/kg PO) in a randomized crossover design. Plasma concentrations of vonoprazan-N-oxide (M-I) and vonoprazan-nitrone (M-III) were quantified using a validated liquid chromatography-tandem mass spectrometry method, and a non-compartmental pharmacokinetic analysis was performed. In vitro metabolism was evaluated using equine liver microsomes (ELMs) and equine recombinant CYP450 (eq-rCYP) enzymes. Enzyme kinetics were characterized using nonlinear regression modeling. Results: Both metabolites were detected in plasma after oral administration. Systemic exposure to M-I was markedly greater than M-III at both doses. At 1 mg/kg, mean ± SD C_max values were 39.2 ± 28.3 ng/mL for M-I and 1.67 ± 1.66 ng/mL for M-III. AUC_0–∞ increased dose-proportionally for both metabolites. In ELMs, M-I formation followed substrate inhibition kinetics, whereas M-III formation followed Michaelis–Menten kinetics. Among recombinant enzymes, CYP2D50 and CYP3A94 were the primary contributors to metabolite formation, exhibiting metabolite-specific kinetic profiles. Conclusions: These findings demonstrate that vonoprazan undergoes hepatic oxidative metabolism in horses, with M-I as the predominant circulating metabolite. Equine recombinants CYP2D50 and CYP3A94 appear to play central roles in equine vonoprazan metabolism, providing foundation for future evaluation of drug–drug interaction potential and clinical use in this species. Full article

Background: The Oxford Hip Score (OHS) is a widely used hip-specific patient-reported outcome measure (PROM) following primary total hip arthroplasty (THA). This measure is calculated from answers to a 12-item questionnaire and can provide indices that indicate clinically meaningful success, such as patient acceptable symptom state (PASS). There were three purposes of the present single-cohort retrospective study: first, to determine the threshold PASS; second, to determine the influence of patient characteristics (age, gender, and body mass index (BMI)) and preoperative OHS and other PROMs of patients (namely, EQ-5D-3L, EQ-VAS, and pain VAS) who did not achieve this threshold; and third, to establish whether failure to achieve the PASS could still be associated with meaningful clinical improvement. Methods: This single-centre retrospective cohort study was conducted over 10 years from January 2013 to December 2022, during which 3997 patients completed pre- and postoperative OHS. The mean age was 68.3 years (standard deviation 11.7), and there were 2375 (59.4%) females in the cohort. Patient satisfaction was used as the anchor to define the PASS. Results: An OHS at 12 months postoperative of ≥36 points was identified as the threshold PASS (area under the curve 88.5%, 95% confidence interval [CI] 87.0 to 90.1, p < 0.001). Overall, 3002 (75.1%) achieved the PASS at 12 months. Lower BMI (odds ratio [OR] 0.96, 95% CI 0.95 to 0.98, p < 0.001) and higher preoperative OHS (OR 1.05, 95% CI 1.03 to 1.06, p < 0.001), EQ-5D (OR 1.88, 95% CI 1.33 to 2.65, p < 0.001) and EQ-VAS (OR 1.02, 95% 1.01 to 1.02, p < 0.001) were independently associated with achieving the PASS at 12 months. A total of 995 patients (24.9%) did not achieve this threshold. Patients not achieving the PASS had clinically meaningful worse (p < 0.001) postoperative outcomes and improvement relative to baseline in OHS, EQ-5D and EQ-VAS when compared to those achieving a PASS. Patients achieving the PASS were more likely to be satisfied with their THA (OR 16.8, 95% CI 12.8 to 22.1, p < 0.001); however, patients not achieving the PASS still had significant (p < 0.001) improvements relative to baseline in their OHS (9.6, 95% CI 9.0 to 10.2), EQ-5D (0.254, 95% CI 0.229 to 0.278), EQ-VAS (1.4, 95% CI −0.3 to 3.1) and pain VAS (8.2, 95% CI 6.1 to 10.3) and were more likely to be satisfied (70.8%) than not (29.2%). Conclusions: An OHS of ≥36 at 12 months was defined as the PASS. In total, 995 patients (29.4%) did not achieve this threshold, and in this group, patients were more likely to be female and have a high BMI and low preoperative OHS, EQ-5D, EQ-VAS, and pain VAS. Despite not achieving the PASS, they reported meaningful clinical improvements in OHS, EQ-5D, and pain VAS, and were satisfied with their THA (70.8%). Full article

Background/Objectives: Older adults residing in long-term care frequently experience multimorbidity, low habitual activity, mobility decline, executive dysfunction, and reduced quality of life. Evidence separating the effects of exercise, cognitive stimulation, and their combination remains limited. The primary objective of this trial is to determine whether a 12-week combined physical exercise plus cognitive stimulation programme improves executive function, functional mobility, and health-related quality of life compared with usual care. Secondary objectives are to estimate the effects of each single-component programme, compare the combined programme with each component, and examine maintenance at six months. Methods: This is a four-arm, parallel-group, assessor-blinded randomised controlled trial in Portuguese long-term care facilities. A total of 140 residents aged 65 years or older, residing in long-term care for at least three months and able to provide informed consent, will be allocated 1:1:1:1 to supervised multicomponent exercise, group cognitive stimulation, combined exercise plus cognitive stimulation, or usual care. Active programmes will be delivered three times weekly for 12 weeks. Assessments are planned at baseline, post-intervention, and six-month follow-up according to the prespecified schedule. Primary outcomes are the Stroop interference score, Timed Up and Go time, and EQ-5D-5L index value at 12 weeks. Analyses will follow the intention-to-treat principle using mixed-effects models; multiplicity across the three primary endpoints will be controlled using Holm’s procedure, and interaction analyses will be exploratory and hypothesis-generating. Results: Recruitment and data collection had not started at manuscript submission; therefore, no participant data are reported. Conclusions: The trial will estimate the effects of the combined programme versus usual care and provide exploratory comparative evidence on the single-component programmes in real-world long-term care. Full article

Background/Objectives: Scoliosis in children leads to complex physical, psychosocial, and functional impairments, yet evidence from low-resource settings is limited. To evaluate health-related quality of life (HRQoL) in Ethiopian children with scoliosis using WHODAS 2.0 and EQ-5D-Y, and to identify clinical and demographic correlates of disability. Methods: A hospital-based cross-sectional study was conducted at CURE Children’s Hospital of Ethiopia (1 April 2024–31 March 2025). Ninety-seven children aged 6–15 years with confirmed scoliosis were assessed. WHODAS 2.0 (36-item) captured disability across six domains, while EQ-5D-Y measured physical, psychosocial, and pain-related HRQoL. Clinical severity indicators (Cobb angle, trunk rotation, thoracic morphometrics, anthropometrics) were recorded. Analyses in Python 3.12 included descriptive statistics, correlation, and multiple regression to examine associations between scoliosis severity and HRQoL outcomes. Results: Ninety-seven Ethiopian children diagnosed with scoliosis (mean age 11.4 years, mean Cobb angle 73.5°) were assessed; congenital scoliosis was most common (45.4%), followed by idiopathic (38.1%) and neuromuscular (16.5%). WHODAS 2.0 revealed substantial disability, particularly in mobility (46.4%) and social participation (62.8%), with life activities and participation as the strongest contributors. Greater deformity, younger age, and smaller body size were linked to worse outcomes, with neuromuscular and very severe thoracolumbar cases most affected. EQ-5D-Y showed marked HRQoL impairments across domains, with psychological distress (mean 2.24/3), pain, and self-care limitations emerging as key burdens. The mean EQ score was 8.89/15 (59.2%), indicating reduced quality of life. Regression analyses highlighted pain, psychological distress, and self-care limitations as the domains most strongly associated with poorer HRQoL, while greater Cobb angle and higher ATR degree were also correlated with reduced quality of life. Conclusions: Ethiopian children with scoliosis experience significant multidimensional impairments in HRQoL, with mobility, social participation, pain, and psychological distress as dominant burdens. WHODAS 2.0 and EQ-5D-Y proved complementary in capturing these impacts, supporting their use for early detection, clinical care, and public health planning in resource-limited settings. Full article

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced cutaneous melanoma care, shifting it from an acutely fatal illness to a chronic, manageable condition. While extending survival, these modern therapies introduce a new spectrum of persistent immune-related adverse events (irAEs) and long-term toxicities. This study aims to explore the “Toxicity-HRQoL Paradox” to comprehensively evaluate the true price of survival across the melanoma treatment continuum. Methods: This narrative review, based on a systematic database search, synthesizes quantitative patient-reported outcomes, health-related quality of life (HRQoL) trajectories, and health-economic data. It evaluates the impact of surgical, regional, and modern systemic therapies utilizing data derived from validated instruments, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EuroQol 5 Dimensions (EQ-5D), Functional Assessment of Cancer Therapy-Melanoma (FACT-M), and comprehensive score for financial toxicity (COST). Results: Historically, extensive locoregional surgeries and high-dose interferons caused profound, debilitating drops in physical and overall QoL. Today, modern systemic therapies are associated with high rates of severe (Grade ≥ 3) acute toxicities and irreversible chronic conditions, such as permanent endocrinopathies. Despite this, global HRQoL frequently remains stable or even improves. This “toxicity-HRQoL paradox” occurs because the profound psychological relief of durable disease control effectively offsets the physical symptom burden. Furthermore, neoadjuvant ICI approaches demonstrate superior long-term HRQoL by enabling tailored surgical de-escalation. Ultimately, extended survivorship unmasks hidden burdens, revealing high prevalences of fear of cancer recurrence (FCR) (81–86%) and substantial financial toxicity. Conclusions: Despite the severe physical toxicities of modern melanoma treatments, the psychological benefit of survival largely preserves overall HRQoL. However, optimizing the modern survivorship experience requires the widespread adoption of melanoma-specific HRQoL tools and proactive, multidisciplinary care models to manage chronic toxicities, psychosocial distress, and financial burdens. Full article

Background/Objectives: Interferon-free direct-acting antiviral (DAA) therapy cures chronic hepatitis C virus (HCV) infection, but its short-term effects on health-related quality of life (HRQoL) are captured differently by generic and disease-specific instruments. We examined longitudinal changes in utility scores and HRQoL in a multicenter Japanese cohort. Methods: Adults with chronic HCV completed the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), the 8-Item Short-Form Health Survey (SF-8), and the Chronic Liver Disease Questionnaire (CLDQ) at baseline and at 12, 24, and 36 weeks after treatment initiation; 48-week data were included when available. Complete-case panels were analyzed for each instrument (SF-8, n = 112; CLDQ, n = 131; EQ-5D-5L, n = 128). Domain trajectories were summarized and compared with baseline. Results: By week 36, SF-8 general health improved significantly from 50.42 to 52.47, whereas vitality (50.73 to 52.55) and mental health (51.02 to 53.05) showed nonsignificant numerical increases. CLDQ showed improvements in worry (5.21 to 5.82) and total score (5.21 to 5.47). EQ-5D-5L utility values remained high and largely stable (0.913 to 0.920), suggesting ceiling effects in patients with relatively good baseline health status. External real-world evidence also suggested better on-treatment HRQoL with ribavirin-free regimens. Conclusions: In Japanese patients with HCV, interferon-free DAA therapy was associated with early improvements in symptom-proximal and mental domains of HRQoL. Generic utility scores changed little over the short term, indicating that disease-specific patient-reported outcome (PRO) instruments and utility measures should be used together for patient-centered assessment and cost–utility modeling. Full article

Objective: The objective was to evaluate longitudinal changes in health-related quality of life (HRQoL) following surgical resection of brain metastases and investigate the prognostic value of the Graded Prognostic Assessment (GPA) score in predicting HRQoL improvement. Methods: This prospective observational study included 42 consecutive adult patients undergoing microsurgical resection for histopathologically confirmed brain metastases. HRQoL was assessed using the EuroQol Five-Dimension Five-Level questionnaire (EQ-5D-5L) questionnaire and EuroQol Visual Analogue Scale (EQ-VAS) preoperatively and at 1 and 6 months postoperatively. Patients were stratified according to their preoperative GPA scores, and longitudinal changes in HRQoL were analyzed using non-parametric statistical methods. Results: Mean EQ-VAS scores exhibited a significant postoperative increase from 38.3 ± 19.3 at baseline to 77.6 ± 19.3 at one month and 75.7 ± 16.7 at six months (p < 0.001). Significant improvements were observed across all five EQ-5D-5L dimensions (all p < 0.001). Patients with favorable GPA scores (3.0–4.0) demonstrated greater improvements in EQ-VAS than those in lower GPA categories at one month (p = 0.035) and six months (p = 0.013). Higher baseline GPA scores were positively correlated with HRQoL improvement at both follow-up time points (ρ = 0.51 and ρ = 0.50, respectively; both p < 0.001). Changes in clinician-rated Karnofsky Performance Status (KPS) did not differ significantly across GPA categories (p = 0.731). Conclusions: Surgical resection of brain metastases significantly improves patient-reported HRQoL. The GPA score is a significant predictor of postoperative HRQoL gain, whereas traditional clinician-rated scales like KPS may lack the sensitivity to capture these patient-centered improvements. However, the findings regarding GPA subgroups should be considered exploratory due to the limited number of patients in certain tiers. Full article

Background: Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are widely prescribed for type 2 diabetes mellitus (T2DM) because of their cardiovascular and renoprotective benefits. However, their use is associated with euglycemic diabetic ketoacidosis (EDKA), a rare but potentially life-threatening complication characterized by severe ketoacidosis despite relatively normal blood glucose levels. Failure to discontinue SGLT-2 inhibitors before surgery, as recommended in current guidelines, together with perioperative fasting and surgical stress, increases the risk of EDKA. Diagnostic complexity is compounded when concurrent postoperative surgical complications provide an alternative explanation for persistent metabolic acidosis. Methods: A 71-year-old man with T2DM receiving uninterrupted empagliflozin underwent direct lateral interbody fusion under general anesthesia. On postoperative day 2, he developed severe high anion-gap metabolic acidosis (pH 7.204, HCO₃⁻ 10.1 mEq/L) with near-normal blood glucose levels (178 mg/dL). Pneumoperitoneum identified on imaging was attributed to Hemovac drain-related peritoneal injury, and emergent laparoscopic exploration was performed under a working diagnosis of surgical sepsis. Although surgical source control was successfully achieved, severe metabolic acidosis persisted postoperatively (pH 7.275). Euglycemic diabetic ketoacidosis is an uncommon diabetic complication associated with several perioperative risk factors, including prolonged fasting and surgical stress. Subsequent serum ketone analysis demonstrated markedly elevated beta-hydroxybutyrate levels (4.8 mmol/L), confirming co-existing EDKA. Results: Following empagliflozin discontinuation, targeted treatment with concurrent insulin–dextrose infusion resulted in complete resolution of acid-base imbalance within five days. Conclusions: A concurrent surgical complication appeared to mask EDKA and contributed to a delay in its recognition. In patients receiving SGLT-2 inhibitors, metabolic acidosis that persists after an apparent surgical cause has been addressed should prompt measurement of serum ketones, irrespective of the blood glucose concentration. Structured perioperative protocols for SGLT-2 inhibitor management and postoperative ketone surveillance may help to prevent similar events. Full article

Haul-road condition in open-pit mining affects fuel consumption, transport-cycle throughput and dump-truck mechanical loading. This study conducted a quasi-experimental field assessment of local maintenance effects on severely degraded road segments. The full cycle register contained 32,000 entries, of which 30,808 passed quality control and were used for background engineering characterization. The primary difference-in-differences (DiD) analysis used 2634 matched-control cycle–focal-segment observations, while 72,000 one-second telemetry records formed a separate 20 h dynamic validation subset. Relative to matched-control dynamics, maintenance increased RCI by 3.26 points and reduced IRI by 6.24 m/km, the apparent rolling-resistance descriptor by 2.71 percentage points and rut depth by 41.2 mm. Regression-adjusted effects were −10.6 L/cycle for fuel, −0.78 min for cycle time, +10.7 km/h for segment speed, −0.351 g for vibration RMS and −78.2 MPa-eq. for the suspension-stress proxy. A 14-day lead-placebo/event-time diagnostic found no detectable pre-intervention divergence, and non-negative cohort-weighted group-time ATT estimates closely matched the TWFE results. The coefficients are interpreted as site-specific local intervention-window effects rather than annual fleet-wide constants. Full article

The environmental management of highly saline coal mine wastewater presents a critical challenge for European mining regions, particularly under the constraints of the EU Water Framework Directive. This study presents a cradle-to-grave life cycle assessment of a novel zero liquid discharge (ZLD) system developed under the EU-funded LIFE Brine-Mining project and deployed at the Ziemowit mine in Poland. The system was designed to treat coal mine brine (TDS ~80 g/L) and recover valuable resources, including high-purity water, sodium chloride, magnesium hydroxide, calcium carbonate, and calcium sulphate. The assessment was conducted in accordance with EN 15804 using the Environmental Footprint v3.1 methodology, ecoinvent v3.10, and a functional unit of 1 m³ of saline wastewater inflow, covering all life cycle stages from raw material extraction to end-of-life and resource recovery (Module D). The results indicate a fossil-based global warming potential of 73.86 kg CO₂ eq. per functional unit, with 66% attributed to operational electricity consumption (module B6, 44 kWh/m³) and 29% to auxiliary chemical consumption (module B1). Three key environmental hotspots were identified: module B1 dominates ozone depletion potential (67%), module B6 dominates acidification potential (66%), and raw material extraction (module A1) dominates abiotic depletion of minerals and metals (43%). Resource recovery credits (Module D) offset 11.80 kg CO₂ eq. of GWP-fossil, cause the ADP-minerals and metals indicator to become net negative, and reduce the water deprivation potential by approximately 50%. A sensitivity analysis confirmed that results are robust to ±10% variations in wastewater inflow, with GWP-total varying within a narrow −0.5% to +0.6% range once the volume-proportional nature of chemical and electricity consumption is correctly accounted for. These findings provide a quantitative sustainability baseline for the scale-up and replication of integrated ZLD technologies in the European mining sector, demonstrating that circular brine treatment can simultaneously address regulatory water quality targets, reduce primary resource consumption, and deliver measurable environmental credits aligned with EU circular economy and sustainable development objectives. Full article

Background: Cervical radiculopathy is a common and disabling condition with both nociceptive and neuropathic pain components. Epidural steroid injections (ESIs) are widely used as an interventional treatment modality; however, the optimal cervicothoracic interlaminar access level and injectate volume remain subjects of ongoing debate. Because injection level and injectate volume have historically been varied together in routine practice rather than independently, prospectively designed comparative data are lacking. Methods: In this retrospective, multicenter cohort study, 166 patients with MRI-confirmed cervical radiculopathy treated between January 2022 and December 2025 at three participating institutions received fluoroscopy-guided cervicothoracic interlaminar epidural steroid injections with dexamethasone and bupivacaine at either C7/T1 (6 mL; n = 87) or T1/T2 (8 mL; n = 79), with protocol determined by the treating institution rather than randomization. The prespecified primary outcome was the baseline-adjusted between-group difference in arm-pain Numeric Rating Scale (NRS) score at 3 months, analyzed by analysis of covariance (ANCOVA) adjusted for a directed acyclic graph-informed covariate set (age, symptom duration, baseline pain severity, number of stenotic levels, DN4 score, and treatment center); the same covariates were used in a generalized estimating equation (GEE) model with a group-by-time interaction and in a multivariable logistic regression for treatment response. Secondary outcomes—neck-pain NRS and VAS, neuropathic pain (DN4), functional disability (NDI), quality of life (SF-36, EQ-5D), Patient Global Impression of Change (PGIC), analgesic consumption, and cardiovascular/metabolic safety outcomes—were assessed at baseline, 3 months, and 6 months. Results: Both groups showed significant within-group reductions in arm-pain NRS (C7/T1: 8.7 ± 0.4 to 3.5 ± 0.4 at 3 months and 4.1 ± 0.6 at 6 months; T1/T2: 9.2 ± 0.7 to 3.9 ± 0.5 at 3 months and 4.9 ± 0.7 at 6 months; both p < 0.001). Baseline pain scores and symptom duration were not balanced between groups (baseline-adjusted analysis was therefore used). After adjustment for baseline severity, age, symptom duration, and center, the T1/T2–8 mL protocol was associated with higher (worse) adjusted arm-pain NRS than the C7/T1–6 mL protocol at 3 months (adjusted difference 0.41 points, 95% CI 0.21–0.61) and 6 months (0.66 points, 95% CI 0.35–0.97); a multivariable-adjusted logistic regression model likewise showed lower odds of achieving a ≥50% arm-pain reduction at 3 months with the T1/T2–8 mL protocol (adjusted OR 0.18, 95% CI 0.04–0.82). NDI decreased from a mean of 48.1 points at baseline to 28.1 points at 3 months (pooled cohort, score capped at the 0–50 scale maximum; the majority of baseline NDI source records could not be individually verified and this is reported as a limitation), and analgesic consumption decreased over follow-up. Among hypertensive patients (45/166, 27.1%), 78% experienced transient blood pressure elevation and 40% required temporary antihypertensive adjustment; among diabetic patients (13/166, 7.8%), 92% developed transient hyperglycemia. Because injection level, injectate volume, and treatment center were confounded by design, these findings should be interpreted as a comparison of two center-specific treatment protocols rather than an isolated effect of anatomical level or volume. Conclusions: Both center-specific cervicothoracic interlaminar epidural steroid injection protocols were associated with improvements in pain and function over six months, with no catastrophic procedural complications documented; however, near-complete confounding of injection level with injectate volume and treatment center, together with imbalanced baseline pain severity, precludes conclusions about the comparative effectiveness of C7/T1 versus T1/T2 access. Transient cardiovascular and metabolic effects were common and support consideration of post-procedural monitoring in patients with pre-existing hypertension or diabetes. Full article