Introduction: Cangrelor has favorable pharmacokinetic properties that make it ideal during neuroendovascular procedures. It exhibits a rapid onset and offset of antiplatelet activity. Due to the balance of bleeding and thrombotic risks, determining an optimal antiplatelet regimen is critical. The purpose of this study was to report the safety and efficacy of periprocedural very low dose cangrelor and assess platelet function testing to optimize antiplatelet therapy. Methods: This retrospective study examined very low dose cangrelor use during neuroendovascular procedures for acute ischemic stroke. Cangrelor was administered as a 7.5-15 mcg/kg IV loading dose, followed by an IV infusion of 0.25-0.5 mcg/kg/minute to patients undergoing stenting or who required treatment of an intraluminal thrombus. Outcomes included safety events (bleeding and thrombotic complications), length of intensive care unit (ICU) and hospital stay, and an examination of platelet function testing. Results: Fifty-six patients received very low dose cangrelor during stenting and/or for intraluminal thrombus treatment. Eleven patients (19.6%) experienced an adverse bleeding event related to cangrelor administration. Eight events were asymptomatic and did not alter antiplatelet management. Two patients experienced thrombotic events during cangrelor infusion. The average ICU and hospital length of stay was 5.2 days and 10.5 days, respectively. Forty-two patients underwent platelet function testing while on cangrelor monotherapy, for which 69% were therapeutic. Conclusions: Very low dose cangrelor may be effective in preventing thrombotic complications with a low rate of symptomatic bleeding events in patients undergoing neuroendovascular procedures. The incorporation of platelet function testing may optimize antiplatelet selection and dosing after a neuroendovascular procedure.

To identify optical coherence tomography and optical coherence tomography angiography (OCTA) biomarkers associated with persistent retinal fluid in treatment-naïve neovascular age-related macular degeneration after three loading doses of anti-vascular endothelial growth factor therapy. In this retrospective study, 60 patients with treatment-naïve typical neovascular age-related macular degeneration received three monthly intravitreal bevacizumab injections. Four weeks after the third injection, patients were categorized as responders (Group 1, n = 30) if no fluid was seen, or as suboptimal responders (Group 2, n = 30) if fluid persisted. Baseline optical coherence tomography and OCTA parameters were assessed, including central macular thickness, subfoveal choroidal thickness, pigment epithelial detachment height, hyperreflective foci, subretinal hyperreflective material, and macular neovascularization morphology. Optical coherence tomography angiography features were analyzed for loop morphology, branching vessels, peripheral arcades, sea fan pattern, and hypointense halo. Vessel density was quantified in the superficial capillary plexus, deep capillary plexus, and choriocapillaris. No significant differences were found between groups in baseline optical coherence tomography parameters (all P > 0.05). Vessel density in the superficial capillary plexus, deep capillary plexus, and choriocapillaris did not differ between groups. However, OCTA revealed that loop morphology ( P = 0.001), peripheral arcade ( P = 0.009), and branching vessels ( P = 0.032) were more frequent in suboptimal responders. On multivariate regression, only loop morphology remained a significant independent predictor of persistent fluid (OR = 4.36, P = 0.036). Loop-shaped neovascular morphology on baseline OCTA independently predicted poor anatomical response to anti-vascular endothelial growth factor therapy. Identifying such features may support early risk stratification and guide personalized treatment strategies.

Severe alcohol withdrawal (SAW) is a common cause of hospital admission in the United States. There has been increased interest in phenobarbital use for SAW treatment. We aimed to investigate variability in alcohol withdrawal management protocols at different hospitals within a geographic region, with a focus on phenobarbital use. We e-mailed a survey to intensive care unit physician leadership to all New York City acute care hospitals as well as large acute care hospitals in Massachusetts regarding their protocols for SAW. Of 13 respondents, eight have SAW protocols, six of whom have a distinct phenobarbital protocol. Phenobarbital load locations were in the emergency department or intensive care unit. Loading doses ranged from 8 to 15 mg/kg. Three protocols recommended an oral/intramuscular phenobarbital taper, and two protocols specified as needed phenobarbital rescue doses on hospital wards. There was some overlap in other rescue medications, but frequency and dose were not specified. Only two respondents of the survey included benzodiazepines as a rescue medication option. There is some evidence that phenobarbital use for SAW has comparable to improved efficacy in certain patient outcomes. It appears that current evidence may have led to the adoption of phenobarbital use in SAW protocols in several urban university hospitals. Our results demonstrate, however, that there is significant irregularity in dosing, tapers, and concomitant benzodiazepine use. Phenobarbital protocols for SAW are common among large urban hospitals, but protocols are not standardized. More research and interhospital collaboration should be undertaken to reduce variability and optimize treatment protocols.

Hand osteoarthritis (OA) is a prevalent and debilitating joint disorder that impairs daily functioning and quality of life. Current treatments are often inadequate in managing the symptoms and progression of the disease. The cytokine interleukin (IL)-17 has been implicated in the inflammatory processes associated with OA, making it a potential target for therapeutic intervention. This trial aims to evaluate the efficacy of vunakizumab, an IL-17A inhibitor, in reducing pain and improving functional outcomes in patients with erosive hand OA. This multicentre, randomised, placebo-controlled, double-blind trial will enrol 150 participants aged 30-80 years with symptomatic erosive hand OA. Participants will be randomised in a 1:1 ratio to receive either vunakizumab 120 mg or placebo subcutaneously every 4 weeks for 24 weeks, with a loading dose injection period during the first 4 weeks. The primary outcome is the change in hand pain assessed by the Visual Analogue Scale at 28 weeks. Secondary outcomes include changes in physical function measured by the Functional Index for Hand Osteoarthritis, the Quick Disabilities of the Arm, Shoulder and Hand questionnaire and the Health Assessment Questionnaire, as well as changes in grip strength and radiographic and MRI evaluations of the hands. Written informed consent will be obtained from all participants. The study was approved by the Ethics Committee of Shanghai Sixth People's Hospital (2024-217) and will adhere to the Declaration of Helsinki. Research results will be published in peer-reviewed journals. ChiCTR2500101031; https://www.chictr.org.cn/showproj.html?proj=264789.

Optimal Switching Antiplatelet Regimen in Patients with Ticagrelor to a Thienopyridine in Korean Patients (SWAPT-K Study).

To evaluate caffeine prescribing practices in a tertiary neonatal unit, focusing on initiation, dose adjustment, discontinuation and recommencement, and to assess associations with gestational age and respiratory support. Retrospective observational study. Neonatal unit, John Radcliffe Hospital, Oxford, United Kingdom. Preterm infants born ≤32 weeks gestation and admitted between 1 February 2022 and 31 October 2023. Data extracted from paper patient records included daily caffeine dosing, initiation, discontinuation, recommencement, coadministration with doxapram, demographics and duration of respiratory support. Associations between caffeine administration and clinical factors such as gestational age were assessed using regression. 168 admissions were analysed from 163 infants. Caffeine was typically initiated with a loading dose of 20 mg/kg, and maintenance doses ranged from 5 mg/kg/day to 25 mg/kg/day. There were 1-8 dose adjustments per admission. Doxapram was administered to 19 infants. Caffeine was discontinued at a median (IQR) postmenstrual age of 34.0 (33.9-34.7) weeks and was recommenced in four infants. Gestational age at birth was negatively correlated with postmenstrual age at discontinuation (r(CI) -0.33 (-0.51 to -0.12), p=0.0029; R²=0.11) and infants born at lower gestational ages received higher doses. Caffeine therapy in this unit showed marked variability in dosing, discontinuation and recommencement, highlighting the individualised nature of bedside decision-making, which may reflect clinical response to therapy.

Introduction: Status epilepticus is initially treated with a benzodiazepine followed by a first-line anti-seizure medication (ASM) such as levetiracetam, valproic acid or fosphenytoin. Despite prompt therapy, up to one-third of patients progress to refractory status epilepticus (RSE). While lacosamide is frequently used in RSE due to its favorable safety profile, its optimal timing and efficacy remain unclear. This study evaluated lacosamide’s effectiveness in seizure cessation based on early (second-line) versus late (third-line or beyond) administration. Methods: This study was a multicentered retrospective review of adult ICU patients with RSE admitted to eight AdventHealth hospitals between July 2022 and March 2024. Patients were excluded if they were allergic to lacosamide or taking it prior to admission. The primary outcome was seizure cessation following lacosamide, defined as the absence of clinical and electrographic seizures without the need for additional ASMs or anesthetic dose escalation. Secondary outcomes included total number of ASMs used, hospital and ICU length of stay, mortality, and adverse effects. Results: Forty-one patients were included, with 25 patients being classified as receiving early lacosamide and 16 patients receiving it later. Baseline characteristics were similar between groups. Initial treatment prior to lacosamide included a median of 2.4 mg lorazepam equivalents in the early group and 3.5 mg lorazepam equivalents in the late group. The most commonly utilized first-line ASM was levetiracetam, with median loading doses of 2,500 mg in the early group and 1,750 mg in the late group. The median loading dose of lacosamide was 200 mg in the early group and 300 mg in the late group. Seizure cessation occurred in 44% (11/25) of early group patients versus 31% (5/16) in the late group (p=0.41). Notably, the early group required significantly fewer total ASMs (p < 0.001). Safety and other secondary endpoints were similar between groups. Conclusions: Early use of lacosamide in RSE was associated with significantly fewer ASMs used and numerically higher rates of seizure cessation, suggesting potential clinical benefit despite lack of statistical significance in the primary outcome. Further studies with larger sample sizes are warranted to validate these results.

Purpose: To compare functional and morphologic outcomes after loading doses of faricimab and high-dose aflibercept for treatment-naive neovascular age-related macular degeneration (nAMD). Methods: We retrospectively enrolled 62 consecutive patients (64 eyes) with nAMD whose initial visual acuity (VA) was ≤20/25. Patients received 3 consecutive monthly loading doses of intravitreal 6.0 mg/0.05 mL faricimab (IVF) or intravitreal 8.0 mg/0.07 mL high-dose aflibercept (IVHDA). Changes in best-corrected VA (BCVA) and fluid were assessed at 4, 8, and 16 weeks compared with baseline. Results: Two patients were excluded from the final analysis, yielding a total of 60 patients (62 eyes). In the IVF group (n = 31 eyes), the logMAR BCVAs at baseline, 4, 8, and 16 weeks were 0.40, 0.35, 0.33, and 0.30, respectively; significant improvement occurred at 16 weeks only (P = .004 vs baseline). In the IVHDA group (n = 31 eyes), the logMAR BCVAs at the respective timepoints were 0.44, 0.36, 0.30, and 0.32; significant improvements occurred at 8 and 16 weeks (P = .001 and P = .007, respectively, vs baseline). At 16 weeks, 90.3% of patients receiving IVF and 80.6% receiving IVHDA had dry macula (P = .473). Conclusion: Significant BCVA improvements were achieved with both treatments, although improvement was faster with IVHDA. High rates of dry macula were achieved at 16 weeks in more patients in the IVF group than in the IVHDA group.

Introduction: High-output stoma (HOS) is a frequent and morbid complication following ileostomy formation. Proton pump inhibitors (PPIs) may reduce intestinal secretions, but no randomized trial has yet tested whether intensified intravenous omeprazole treatment prevents or mitigates early postoperative HOS. We aim to determine whether intensified PPI dosing reduces early postoperative ileostomy output compared with standard dosing. Methods and Analysis: STOP-HOS-1 is a randomized, parallel-group, open-label, superiority trial conducted at two academic centers in Poland. The target sample size is 100 adults undergoing the formation of a loop or end ileostomy. Participants will be randomized 1:1 to receive either: intensified omeprazole group—80 mg IV loading dose, followed by 40 mg IV twice daily through postoperative day (POD) 10, or standard omeprazole group—40 mg IV once daily through POD 10. The primary outcome is mean ileostomy output (mL/24 h) across POD 1–3. A ≥250 mL/day reduction is prespecified as clinically meaningful. Key secondary outcomes include: incidence of HOS (≥1000 mL/day for ≥3 consecutive days or ≥1400 mL on any single day), time to output stabilization (<1400 mL/day for 3 consecutive days), dehydration-related complications (hyponatremia, hypokalemia, acute kidney injury), length of hospital stay and 30-day readmission rate. The primary analysis will follow the intention-to-treat principle. One interim safety analysis is planned after enrollment of the first 20 patients. Discussion: Although PPIs are commonly used to reduce ileostomy output, high-quality evidence in the early postoperative setting is lacking. STOP-HOS-1 targets the critical period when output is most variable, and complications are most frequent, using a pragmatic randomized design and an objective, clinically meaningful primary endpoint. Conclusions: STOP-HOS-1 will provide the first randomized evidence on whether intensified postoperative PPI therapy reduces early ileostomy output and HOS-related morbidity, informing future standards of care.

Bleeding peptic ulcers remain a major cause of non-variceal upper gastrointestinal hemorrhage, and optimizing post-endoscopic pharmacologic therapy is essential to reducing early rebleeding and improving clinical outcomes. This study evaluated the therapeutic effectiveness of high-dose versus low-dose omeprazole following endoscopic hemostasis. This retrospective observational study included patients with endoscopically confirmed bleeding peptic ulcers treated between August 2022 and August 2025. Patients received either high-dose omeprazole (80-mg intravenous loading dose followed by continuous infusion at 4 mg/h) or low-dose omeprazole (40 mg intravenously once daily) after endoscopic hemostasis. Hemoglobin, hematocrit, rebleeding rates, clinical recovery parameters, and adverse events were collected. Participants were followed for 30 days to evaluate delayed rebleeding. Continuous variables were analyzed using independent-samples t tests, and categorical variables using chi-square tests. A total of 119 patients were included (high-dose: n = 58; low-dose: n = 61). High-dose omeprazole significantly reduced rebleeding at 72 hours (6.9% vs 21.3%, P = .025) and 30 days (10.3% vs 29.5%, P = .009). Greater increases in hemoglobin and hematocrit, lower transfusion volume, faster cessation of bleeding, earlier hemodynamic stabilization, and shorter hospitalization were also observed (all P < .001). Adverse event rates were comparable between groups. High-dose omeprazole combined with endoscopic hemostasis enhances hemostatic stability, accelerates clinical recovery, and reduces short-term rebleeding without increasing treatment-related adverse events.

To evaluate short-term real-world outcomes after switching to faricimab using a modified treat-and-extend (TAE) regimen with a single loading dose in patients with retinal vein occlusion (RVO) refractory to prior anti-VEGF therapy. In this prospective study, 27 eyes of 27 patients with macular edema (ME) secondary to RVO and persistent intraretinal fluid (IRF) and central subfield thickness (CST) ≥ 270 μm despite ≥ 3 prior anti-VEGF injections at treatment intervals ≤ 6 weeks were switched to faricimab. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including CST, IRF, and subretinal fluid (SRF), were assessed from baseline (1st faricimab injection) until 3rd faricimab injection (final visit). Outcomes were analyzed for all RVO combined and stratified by central (CRVO) and branch retinal vein occlusion (BRVO). In the all RVO combined cohort, median BCVA improved significantly from 0.2 logMAR to 0.1 logMAR (p = 0.022), and median CST decreased from 291 μm to 268 μm (p < 0.001) over a mean follow-up of 11.7 weeks. The proportion of eyes with IRF was significantly reduced (p < 0.001), and a dry macula was achieved in 48.1% of eyes at the final visit. The mean treatment interval increased significantly from 4.6 to 7.3 weeks, with an intended interval extension achieved in 88.9% of eyes. After stratification, both CRVO and BRVO subgroups showed significant CST reduction and significant treatment interval extension, while BCVA improved numerically in both subgroups without reaching statistical significance. No safety-related adverse events were observed. In real-world practice, switching to faricimab using a modified TAE regimen with a single loading dose appears to be effective in RVO patients refractory to prior anti-VEGF therapy, yielding significant functional improvement with early interval extension and no safety concerns. German Clinical Trials Register (DRKS) registration ID: DRKS00036984.

Most patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) require maintenance treatment. We aimed to determine whether combined treatment with intravenous immunoglobulin (IVIg) and intravenous methylprednisolone (IVMP) increases remission rates compared with IVIg and placebo. We performed a randomised, double-blind, placebo-controlled study. Adults with CIDP who were treatment naive, relapsed after a remission or required continued treatment after a single IVIg dose were included. Participants were treated with IVMP (1000 mg) or placebo (sodium chloride) every 3 weeks for 18 weeks. All participants received IVIg treatment consisting of a loading dose (2 g/kg) and serial maintenance treatments (1 g/kg). The primary outcome was remission, defined as sustained improvement on disability scales at 52 weeks without need for further treatment. Enrolment was halted after the inclusion of 77 of the 96 planned participants because of safety concerns: four thromboembolic events occurred in the IVIg/IVMP group compared with none in the IVIg/placebo group. 14 of 37 (38%) participants in the IVIg/IVMP group were in remission at 52 weeks compared with 11 out of 40 (28%) in the IVIg/placebo group, with a difference of 10% (95% CI -11 to 31; p=0.47). Several secondary outcomes showed a greater magnitude of improvement in disability and impairment at 18 and 52 weeks in the IVIg/IVMP group. The study was prematurely stopped due to safety concerns after four thromboembolic events in the IVIg plus IVMP group. Combined treatment did not lead to significantly more frequent remissions than IVIg alone in the doses used in this study. ISRCTN15893334.

Objective. To conduct a population pharmacokinetic analysis of polymyxin B (PMB) loading dose in patients with sepsis depending on pathogen resistance. Material and methods. To assess pharmacokinetics of PMB in patients with sepsis (n=36), we took blood samples after administration of loading dose and reaching steady-state plasma drug concentrations. PMB concentrations were determined using enzyme-linked immunosorbent assay. Dose simulations (200, 250, 300, and 350 mg) were performed using Monte Carlo method. Results. In the loading dose group (n=10), mean area under pharmacokinetic curve (AUC12) was 28.6±5.6 mg×h/L, maximum concentration — 5.7±1.8 mg/mL. In the steady-state group (n=26), mean AUC12 reached 35.2±15.6 mg×h/L with peak concentration 5.4±1.98 mg/mL. To assess efficacy of loading dose regimens for infection with pathogens with different minimum inhibitory concentrations (MICs), we analyzed probability of target attainment (PTA) for AUC/MICs 50—100 mg×h/L. Modeling the pharmacokinetics of PMB against carbapenem-resistant organisms showed that efficacy decreased significantly (only 23.8%) at maximum dose of 350 mg for MIC 1 mg/mL. Conclusion. Results demonstrated high efficacy of polymyxin B against carbapenem-resistant organisms with MIC ≤0.5 mg/L and probability of target attainment of &gt;99%. However, MIC ≥1 mg/L require high doses (&gt;300 mg) to achieve significant clinical efficacy. At MIC &gt;1 mg/mL, efficacy is significantly reduced even at maximum dose 350 mg.

Dexmedetomidine sedation in elderly patients is associated with cognitive benefits due to its biomimetic non-rapid eye movement (NREM) sleep–like state. However, this state may predispose patients to periodic limb movements (PLMs), which can cause unintended procedural risk during sedation. We aimed to determine the incidence of PLMs during dexmedetomidine-based multimodal sedation for transcatheter aortic valve implantation (TAVI) and explore associations with the need for conversion to general anesthesia. In this prospective observational study, 35 consecutive patients (mean age 81 ± 6 years; 17 female, 18 male) undergoing TAVI over a two-month period from October 2021 to the end of November 2021 were monitored using standard anesthesia monitoring, processed electroencephalography (pEEG) monitoring using Narcotrend 3-lead frontal EEGs (Narcotrend, Hannover, Germany), and bilateral ankle actimetry (SOMNOwatch™ plus). Sedation was administered according to our institutional protocol, beginning with a dexmedetomidine loading dose (0.5 µg kg⁻¹), followed by titration of the infusion between 0.2 and 1.5 µg kg⁻¹ h⁻¹. Additional propofol or fentanyl boluses were administered as clinically indicated by the responsible anesthesiologist. Actimetry, EEG patterns, and intraoperative events were analyzed. PLMs (2–6 movements/min; most commonly 3–5 movements/min) were observed in 20 of 35 patients (57%) and all conversions to general anesthesia (5/5, 100%) occurred in the PLM-positive group, highlighting a potential clinical impact on procedural stability. In the 19 patients with complete EEG datasets, Narcotrend indices during dexmedetomidine-only sedation averaged 96.6 ± 2.6, consistent with an awake–sedate EEG pattern. Following propofol administration, the index decreased to 39.3 ± 20.0, corresponding to a very large effect size (Cohen’s d = 2.85). Five conversions to general anesthesia were necessary in patients with PLMs, because of restlessness, although the severity of PLMs did not predict conversion. No patient had a known history of restless legs syndrome (RLS); prior neurological disease showed no consistent association with PLM occurrence. PLMs are common during dexmedetomidine sedation for TAVI in elderly patients and may need conversion to general anesthesia. While dexmedetomidine offers cognitive benefits, the potential for movement-related procedural risk warrants increased monitoring and consideration during patient selection and anesthetic planning. Further studies comparing sedation-induced and natural sleep PLMs are needed.

To evaluate the steady-state pharmacokinetics (PK) and glucodynamic effects of insulin efsitora alfa (efsitora) over a weekly interval in adults with type 2 diabetes (T2D). This open-label, multiple dose, euglycaemic clamp study was conducted in 56 insulin naïve adults with T2D (mean [±SD] age, 61.9 ± 5.98 years; HbA1c, 7.1 ± 0.64%; BMI, 31.7 ± 3.20 kg/m2). Following a dose-finding lead-in period with once-daily degludec, eligible participants received a one-time loading dose of 12 U/kg efsitora followed by 9 weekly doses of 4 U/kg. Three 24-h clamps were conducted on Days 1, 4, and 7 after the last efsitora dose. Model-based interpolation was used to derive the glucodynamic profile over the weekly dosing interval at steady-state. Model-predicted pharmacokinetic steady-state was achieved between the 4th and 6th weekly dose of efsitora when using a one-time loading dose. At steady-state, the PK profile over the week had a low peak-to-trough ratio of 1.16, with a half-life of 19 days. The model-predicted glucose infusion rate profile, over the weekly dosing interval, demonstrated a stable glucose-lowering effect of efsitora. The maximum glucose infusion rate occurred between Days 4 and 5. Efsitora showed an even distribution of the glucose-lowering effect within a weekly dosing interval, with a peak-to-trough ratio of 1.07. Efsitora was safe and well tolerated. Efsitora demonstrated a flat, prolonged PK profile, providing a consistent level of insulin exposure at steady-state and resulting in a stable glucose-lowering response across the weekly dosing interval.

Diabetic macular edema (DME) is a leading cause of vision impairment in individuals with diabetes, often treated with anti-vascular endothelial growth factor (anti-VEGF) therapies, such as Avastin® (bevacizumab) and Eylea® (aflibercept). The study objective is to assess the cost-effectiveness of bevacizumab and aflibercept under treat-and-extend (T&E) and pro re nata (PRN) regimens in managing DME in a real-world clinical setting. A field-based retrospective study was conducted at a public tertiary eye hospital in Baghdad, Iraq, from October 2024 through March 2025. The study employed a retrospective design, extracting clinical and treatment data from patients' medical records. Additional economic and sociodemographic information was collected through face-to-face interviews conducted by the first author between October 2024 and March 2025. A total of 394 adult patients with DME were included and categorized into six groups; two loading doses groups (LD)-LD Avastin (n = 206) and LD Eylea (n = 188)-and four maintenance doses (MD) groups-T&E Avastin (n = 139), T&E Eylea (n = 124), PRN Avastin (n = 67), and PRN Eylea (n = 64). Clinical outcomes included best-corrected visual acuity (BCVA; measured as logarithm of the minimum angle of resolution [log MAR]) and central macular thickness (CMT). Costs were calculated from the payer's perspective, incorporating medication, and patient costs. Incremental cost-effectiveness ratios (ICERs) were computed for each regimen. The study included 394 patients, each with one eye affected by DME, categorized into six groups. Based on the chosen LD, 206 patients received six monthly LD of Avastin, and 188 patients received five monthly LD of Eylea. Thereafter, on the basis of the maintenance treatment regimen chosen (MD), 67 patients were assigned to the PRN Avastin treatment group, 64 patients were assigned to the PRN Eylea treatment group, 139 patients were assigned to the T&E Avastin group, and 124 patients were assigned to the T&E Eylea group. During the loading phase, Eylea LD achieved a significantly greater mean utility gain than Avastin LD (0.0909 ± 0.0117 versus 0.0221 ± 0.0106; p = 0.0001). In the maintenance phase, both T&E regimens provided significantly higher utility gains than PRN strategies. PRN Avastin yielded the lowest utility gain (0.0066 ± 0.0072), while PRN Eylea showed modest improvement (0.0278 ± 0.0148; p = 0.0001). Despite superior utility outcomes, Eylea-based regimens exceeded the willingness-to-pay threshold, whereas T&E Avastin remained the most cost-effective option. The study suggests that Avastin under the T&E regimen is the most cost-effective treatment for DME, providing significant savings while maintaining effective management of the condition. These findings can guide therapeutic decision-making for DME in resource-limited settings and countries.

Persistent diabetic macular edema (DME) remains a leading cause of vision loss in diabetic retinopathy, even with anti-VEGF therapy. About 30-40% of patients respond poorly after standard loading doses, resulting in prolonged disease and increased treatment burden. Early identification of high-risk patients is essential for optimizing therapy and reducing unnecessary interventions. This study aimed to develop and compare machine learning models integrating optical coherence tomography (OCT)-derived biomarkers with clinical features to predict persistent DME after anti-VEGF therapy and identify key predictors. This retrospective study analyzed 339 patients with DME treated with anti-VEGF injections at Changhai Hospital between January 2018 and December 2022. Eight predictive models (M1-M8), including logistic regression, LASSO, XGBoost, random forest (RF), and support vector machine (SVM), were constructed using baseline clinical and OCT data. Model performance was assessed by AUC, accuracy, precision, recall, and F1-score. DeLong's test was used for AUC comparison, decision curve analysis (DCA) for clinical utility, and SHAP values for model interpretability. Models integrating OCT biomarkers and clinical features outperformed single-modality models. SVM (M8), XGBoost (M6), and RF (M7) achieved the highest validation AUCs (0.865, 0.819, and 0.812, respectively), demonstrating strong discrimination in the internal validation cohort. DeLong's test confirmed significant AUC improvements for multimodal and regularized models compared with clinical-only models (P < 0.05). SHAP analysis highlighted diabetes duration, ellipsoid zone (EZ)/external limiting membrane (ELM) disruption, and hyperreflective foci (HF) as key predictors. Machine learning models integrating OCT-derived structural biomarkers with clinical features provide superior predictive accuracy for persistent DME compared with conventional models. SHAP-based interpretation consistently identified diabetes duration, EZ/ELM disruption, and HF as key predictors. Among the developed models, SVM achieved the highest AUC in the internal validation cohort, whereas XGBoost and RF provided a favorable balance between predictive performance and interpretability, supporting their potential use in individualized treatment planning.

Vancomycin is commonly used to treat Staphylococcus aureus infections. In critically ill patients receiving continuous renal replacement therapy (CRRT), adsorptive membranes like oXiris may alter drug pharmacokinetics. This retrospective study developed a population pharmacokinetics (PopPK) model using MonolixSuite software, incorporating adsorptive membrane use as a covariate. The final one-compartment model estimated that the population volume of distribution of vancomycin was 94.97 L (RSE 10.5%) and population clearance was 2.82 L/h (RSE 19.0%). Adsorptive membrane use was a significant covariate, slightly increasing vancomycin clearance, while aging was associated with reduced clearance. Monte Carlo simulations indicated that a regimen of 2 g loading dose followed by 1 g every 24 h achieved an AUC0-24/MIC ≥ 400 mg h/L in more than 90% of patients. Individualized vancomycin dosing in this population should consider membrane type, along with patient-specific factors such as age, to optimize therapeutic outcomes.

To evaluate the effects of loading dose and 12months of faricimab treatment on visual function, retinal anatomy, and fluid dynamics in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Patients received intravitreal faricimab 6mg monthly (to Month 4) followed by personalized treat-and-extend regimens allowing 4-week interval adjustments. Best-corrected visual acuity (BCVA), retinal anatomy, and fluid dynamics (evaluated using an artificial intelligence-based automated fluid quantification system) were assessed monthly to Month 4, then at Months 6, 9, and 12. Fifty-one patients (57 study eyes; mean [SD] BCVA: 66.5 [13.4] letters; mean [SD] central retinal thickness [CRT]: 340.7 [84.7] μm at baseline) were enrolled. Significant improvements in mean BCVA (+ 3.3 letters; P < 0.001) and CRT (- 70.5μm; P < 0.001) were observed by Month 4. Maximal pigment epithelium detachment (PED) height reduced significantly from baseline to Month 4. Improvements were maintained to Month 12. Intra- and subretinal fluid and PED volumes were significantly reduced versus baseline at all time points. At Month 12, 73.3% of patients were on treatment intervals of 12weeks or longer. Three adverse events were observed, including one mild intraocular inflammation. Treatment with faricimab resulted in rapid and sustained functional and anatomical improvements in treatment-naïve nAMD.

Background: Bone and joint infections (BJIs), including osteomyelitis, septic arthritis, and periprosthetic joint infections, typically require prolonged antimicrobial therapy and often involve complex outpatient management. Oritavancin, a long-acting lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive bacteria, has emerged as a potential off-label option for BJIs owing to its favourable pharmacokinetic and pharmacodynamic properties. Objectives: To provide a comprehensive overview of the pharmacological rationale, microbiological activity, and available clinical evidence supporting the use of oritavancin in BJIs. Methods: A comprehensive narrative review of the literature was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL), focusing on publications from 2011 to 2025. Observational studies, case series, and case reports describing the off-label use of oritavancin in BJIs were considered. Results: The available literature primarily consists of observational studies and real-world experiences. Eighteen studies met the inclusion criteria. Oritavancin was most frequently evaluated for osteomyelitis (n = 14 studies), prosthetic joint infections (n = 10) and septic arthritis (n = 5). Multi-dose regimens, typically including a 1200 mg loading dose followed by weekly doses of 800-1200 mg, were the most commonly described strategies. Reported clinical success rates generally ranged from approximately 70% to over 90%. Oritavancin was overall well tolerated, with adverse events being mostly mild and self-limiting. Conclusions: Current evidence suggests that oritavancin may represent an effective and well-tolerated off-label option for selected patients with Gram-positive BJIs. Its use may offer practical advantages, including reduced hospitalization and avoidance of prolonged intravenous antimicrobial therapy, particularly in patients for whom standard treatment approaches are challenging.