Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

Generalized myasthenia gravis (gMG) is a chronic autoimmune disorder that causes muscle weakness. This human factors (HF) validation study aimed to demonstrate that use of a prefilled syringe with needle safety device (PFS-SD) or autoinjector (AI) is safe and effective for patients with gMG, caregivers, and healthcare professionals (HCPs) to administer injectable medication in the intended use environments without preventable use errors. Patients with gMG, caregivers, and HCPs were randomized to the PFS-SD or AI. No training on either device use was provided. The safety and usability of both devices were assessed using simulated use scenarios, knowledge-based questions, and participant feedback. The simulated use scenario was successfully completed by 94% and 96% of participants using the PFS-SD and AI, respectively, while 90% and 87% of participants, respectively, successfully administered their assigned dose. Device acceptability was reported by 93% and 100% of patient participants for the PFS-SD and AI, respectively. This HF validation study demonstrated that the PFS-SD and AI are safe and effective for use by patients with gMG, caregivers, and HCPs in the intended use environments.

Nosocomial infections are infections acquired during the receipt of medical care that were neither present nor in the incubation stage at the time of admission. This study examined infection prevention and control (IPC) practices among healthcare workers (HCWs) in primary healthcare centers (PHCCs) in Abha City, Saudi Arabia. A cross-sectional study was conducted among HCWs in PHCCs using a structured, self-administered questionnaire to assess sociodemographic characteristics and IPC practices. Participants included physicians, dentists, nurses, technicians, laboratory staff, and other healthcare professionals. HCWs who had received IPC training in the past year demonstrated higher practice scores (mean = 21.97, SD = 4.70) than those without recent training (mean = 19.31, SD = 3.95; P < 0.001). Consistent adherence to core behaviors was observed, with 79.4% routinely using gloves during high-risk procedures and 71.6% performing hand hygiene with detergent after patient contact. However, important gaps persisted: 54.4% reported always recapping used needles, and only 45.6% consistently treated infectious waste with disinfectants, indicating substantial room for improvement in waste management and needle safety practices. Overall IPC practices showed acceptable adherence in key areas such as glove use and hand hygiene, but unsafe behaviors related to waste disposal and needle handling remain common. Targeted educational interventions and regular training are needed to strengthen IPC practices and reduce the risk of nosocomial infections in PHCCs in Abha.

Childhood immunization is essential to public health; however, vaccination coverage among First Nations communities in Canada remains suboptimal. We conducted our rapid review as the initial phase of a broader project to improve childhood immunization in Canadian First Nations communities using a rigorous, systematic approach often lacking in traditional literature review. We systematically synthesized existing evidence, identified key barriers and enablers, and highlighted critical research gaps, providing a foundation for community-driven research and culturally safe interventions. Following Cochrane Rapid Reviews Methods Group guidelines, we searched Web of Science, PubMed, and Scopus for peer-reviewed studies published between 2003 and 2023. Eligible studies were limited to those published in English and focused on Canadian First Nations populations, reporting on factors influencing childhood immunization. We synthesized findings thematically, identifying patterns in barriers and enabling conditions. We synthesized findings thematically, identifying patterns in barriers and enabling conditions. Four studies met the inclusion criteria. The data revealed three overarching domains: caregiver-related, provider-related, and system-level factors. Barriers at the caregiver level included fear of needle pain, misinformation, safety concerns, difficulty scheduling, transportation issues, and child illness. Provider-related barriers involved communication challenges, limited availability, and perceived disrespect. At the system level, rigid appointment systems, long wait times, and fragmented immunization records were identified as key obstacles. Conversely, enablers of childhood immunization included strong relationships with healthcare providers, culturally respectful care, awareness of disease threats, on-reserve service availability, flexible delivery models, improved data-sharing infrastructure, and community involvement. Addressing these issues requires comprehensive community-based public health strategies that consider cultural, logistical, and systemic dimensions. These interventions should prioritize enhancing cultural safety, engaging communities, improving provider communication, and ensuring accessible, flexible immunization services, supported by robust information-sharing systems.

Guselkumab is approved for the treatment of psoriasis, psoriatic arthritis, as well as ulcerative colitis and Crohn's disease. Two delivery devices for subcutaneous (SC) injection previously had been approved for the administration of 100mg guselkumab. This study was designed to demonstrate the bioequivalence and tolerability of guselkumab following a single-dose SC administration of 100mg guselkumab using a 1mL prefilled syringe (PFS) assembled with an Ypsomate autoinjector (i.e., 1mL PFS-Y, Test device) as compared to the approved 1mL PFS assembled with the UltraSafe Plus needle safety guard (i.e., 1mL PFS-U, Reference device). Mean serum guselkumab concentration-time profiles were nearly superimposable for both devices following a single SC injection. The geometric mean ratios and the corresponding 90% confidence interval [CI] for Cmax and AUCinf were 102.28% (94.85%-110.30%) and 102.10% (95.19%-109.51%), respectively. There were no significant differences in the incidence of treatment-emergent adverse events between the two treatment groups, and the incidence of treatment-emergent anti-drug antibodies was low and comparable between the two groups. Overall, these results suggest that the pharmacokinetics, safety/tolerability, and immunogenicity of guselkumab are comparable when administered via the 1mL PFS-Y and 1mL PFS-U.

AudienceThis innovation aims to educate medical students, physician assistant students (PA), and medical residents across various levels.BackgroundSkin abscesses are frequently encountered in clinical practice, and incision and drainage (I&D) is a common treatment performed in both emergency and outpatient settings.1,2 For advanced practice providers (APPs) and emergency medicine residents, learning this technical skill is particularly important, given the prevalence of abscesses in primary care and urgent care settings. At the Medical University of South Carolina (MUSC), PA students are taught this procedure during the didactic phase of their clinical skills and procedures course.However, the cost of supplies for teaching this procedure has been a significant expense for the program, with commercial abscess task trainers ranging from $22.09 for a Pocket Nurse single-use pad to $65.99 for a SurgiReal tissue pad.3 In contrast, our model cost is approximately $198 for ~100 learners, demonstrating substantial cost savings for resource-limited programs.This manuscript offers a comprehensive guide for crafting an innovative, cost-effective, and true-to-life simulation model designed specifically for I&D training for healthcare practitioners. The materials required for this model can be conveniently sourced from Amazon.com. The proposed technique aims to significantly enhance the educational experience of healthcare practitioners as they acquire these vital clinical skills.Educational ObjectivesUpon completing this lab session, the participant should have the capability to: 1) describe the indications, contraindications, and reasons for performing I&D of an abscess, 2) select the necessary equipment for performing I&D of an abscess, 3) demonstrate the necessary steps for performing an I&D procedure on a simulated abscess.Educational MethodsThe lab was designed for an 8:1 trainee-to-instructor ratio and a 45-minute duration, and utilized paintballs inserted under rolled pizza dough to simulate “skin.” Trainees practiced using lidocaine, syringes, and needles with sterile water, and performed the field block technique. They made incisions in the “abscess” using scalpels, expressed “purulent” material (white paint), removed the “capsule” (paintball shell), and swabbed the material with sterile swabs. Materials included Chux pads, pizza dough, paintballs, gloves, alcohol swabs, needles, syringes, sterile water, scalpels, and applicators, costing $198.06 in total, or $9.56 per student, mostly purchased from Amazon.com.Research MethodsA Redcap survey was distributed to evaluate the effectiveness of an abscess drainage lab in meeting predefined learning objectives. The survey, sent to 188 students, received a 35% response rate. Participants were asked five questions, rated on a 5-point Likert scale, assessing the lab’s value in teaching incision and drainage (I&D), field block, and needle safety. Responses were dichotomized into “disagree/strongly disagree” and “agree/strongly agree.”ResultsThe lab was positively evaluated, with 86.15% (95% CI 75.3–93.5) of respondents recommending the lab be repeated, and 81.82% (95% CI 70.4–90.2) stating the lab provided a realistic simulation of abscess drainage. Additionally, 84.85% (95% CI 73.9–92.5) of participants reported improved confidence in performing I&D, 87.88% (95% CI 77.5–94.6) felt their field block skills improved, and 93.94% (95% CI 85.2–98.3) expressed increased comfort with needle safety.DiscussionThe simulation lab teaches crucial skills such as abscess incision and drainage, field block dexterity, and needle safety during lidocaine preparation. It offers a safe environment for students to practice these skills before patient interaction in clinical settings, using cost-effective materials like paintballs and pizza dough. Similar low-cost abscess simulation models have been described, including reusable ultrasound-guided training methods, further supporting the value of inexpensive, reproducible alternatives for procedural education.4 Although cyst wall removal is included in the simulation checklist, in actual practice this is often not attempted during acute drainage when inflamed. Patients are generally referred to outpatient surgery for follow-up.While there are limitations to this method, including inability to practice breaking up loculations and limitations of the authenticity of the pizza and paintballs, the cost-effectiveness of the lab allows for students an engaging avenue to practice these skills and gain confidence prior to entering clinical rotations. Also, the low response rate among students surveyed likely is secondary to delay between the lab and survey distribution, and could be improved with repeating this study with a shorter time interval between lab and survey with another cohort. Future studies could evaluate the pizza and paintball model in a noninferiority design compared to commercial task trainers to determine whether this cost-effective method maintains equivalent educational quality in programs with greater resources. While there are limitations in the response rate among students surveyed, the overall results reveal that utilizing this method improves student confidence in I&D, needle safety, and field block technique. The pizza and paintball I&D lab provides a cost-effective simulation of I&D and field blocks that can be replicated for use in other medical education programs.TopicsAbscess incision and drainage, cost-effective training, simulation, I&D.

Bepirovirsen, an antisense oligonucleotide in development for the treatment of chronic hepatitis B virus (HBV) infection, is administered from glass vials as a subcutaneous (SC) injection by healthcare professionals (HCPs). A ready-to-use prefilled syringe (PFS) assembled with a safety syringe device (SSD) has been developed to make administration more convenient and facilitate patient self-administration. This Phase 1, open-label, randomized, parallel-group study evaluated the relative bioavailability of bepirovirsen delivered from a vial or PFS SSD, assessed the viability of PFS SSD self-administration, and evaluated the safety and tolerability of SC bepirovirsen in healthy participants. Participants (N = 159) received a single 300 mg SC dose of bepirovirsen administered by a HCP (vial [n = 46] or PFS SSD [n = 49]), or self-administered (PFS SSD, with [n = 32] or without [n = 32] training from a HCP). Relative bioavailability (primary endpoint) of HCP-administered bepirovirsen delivered by vial versus PFS SSD was assessed using maximum observed plasma concentration (Cmax) and area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-inf)). Participants were monitored for adverse events. Bepirovirsen exposure was bioequivalent when HCP-administered either by vial or PFS SSD; the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) were within the standard bioequivalence reference range, 0.80-1.25, for both Cmax (1.02 [0.91-1.14]) and AUC(0-inf) (1.05 [0.96-1.15]). Self-administration using PFS SSD achieved bioequivalence for bepirovirsen exposure compared with HCP administration. No new safety concerns were identified. These findings confirm that PFS SSD is a viable alternative to vials for bepirovirsen administration, when HCP- or self-administered, for the treatment of chronic HBV. Clinical trial identifier: NCT06058390.

Needlestick injuries remain a significant source of bloodborne pathogen exposure in clinical settings, contributing to healthcare-associated infections among nurses. Existing safety devices rely on user compliance or administrative controls, which are insufficient under real-world pressures. This study evaluates the infection control potential of a nurse-designed retractable safety needle (RSN), developed to structurally reduce exposure risk through substitution-level engineering, as defined by the Hierarchy of Controls framework of the US National Institute for Occupational Safety and Health. A randomized crossover trial was conducted with 76 nurses at a regional teaching hospital in eastern Taiwan. Participants completed two simulated clinical injection tasks, once with a conventional cap-type safety needle (CSN) and once with an RSN. Safety and usability outcomes were compared using generalized estimating equations, accounting for within-subject and sequencing effects. Compared with the CSN, the RSN significantly reduced near-miss events (mean difference: -0.62 occurrences, P = 0.002), frequency of needle exposure (mean difference: -7.47 occurrences, P < 0.001), and cumulative duration of needle exposure (mean difference: -27.68 s, P < 0.001). While the RSN demonstrated improved safety outcomes, it required significantly longer preparation time (mean difference: 75.6 s, P < 0.001). Usability scores did not differ significantly between the devices (P = 0.156). The RSN offers a practical infection control innovation by structurally eliminating exposure pathways rather than relying on downstream behaviour. This study supports nurse-led device development in advancing engineering-based strategies to reduce occupational exposure and improve injection safety. Findings may inform future implementation of medication preparation systems to mitigate healthcare-associated infections in practice.

Phenotypic plasticity in traits related to plant water relations and hydraulics is fundamental for the adjustment of trees to rapid climate change. It is not fully understood how conifers can acclimatize their hydraulic system and foliage to a reduction in water availability. For the economically important species Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), we assessed the acclimation potential to a drier climate for mature trees of a common seed source by exploring the phenotypic plasticity of 15 hydraulic and water status-related traits across a steep precipitation gradient in the North German lowlands. Branch embolism resistance (P12, P50), turgor loss point (ΨTLP), hydraulic safety margin (HSM), Huber value, foliage area, needle lifespan and leaf mass δ18O and δ13C were measured. Across the 10 study sites, precipitation explained a large proportion of the variance in P12, P50, ΨTLP, leaf δ18O and δ13C and Huber value, while its influence on foliar traits was small. P12 and P50 became more resistant by ~ 0.2MPa and ΨTLP decreased by ~ 0.1MPa with a precipitation reduction by 310mmyear-1, indicating a significant increase in HSM with increasing climatic aridity; however, the extent of adjustment was small. Contrary to expectation, needle lifespan and foliage area increased, while Huber value decreased, with a reduction in precipitation, suggesting greater foliage drought exposure at drier sites. We found fairly high plasticity in hydraulic and foliar traits and enhanced embolism resistance in drier climates, which might distinguish Douglas-fir from other conifers. However, the Huber value reduction with decreasing precipitation suggests drought vulnerability in drier lowland regions.

Abstract Background Promoting appropriate IV to oral switch (IVOST)1 is a fundamental antimicrobial stewardship (AS) initiative providing benefits for patients, staff and the environment including: reduced risk of cannula related infections, medicine costs, nursing workload and carbon footprint.1,2 A grassroots quality improvement (QI) initiative, highlighting the high oral bioavailability (&amp;gt;90%) of metronidazole and environmental benefits of IVOST in surgical wards at the Royal Alexandra Hospital (RAH), resulted in a 45% median reduction in IV administrations.3 Scale and spread of successful small scale QI initiatives,4 although challenging in the complex healthcare environment, is essential to maximize patient benefits and support attainment of national targets for antimicrobial resistance (AMR)5 and environmental sustainability.6 Objectives This study set out to scale and spread the QI initiative promoting metronidazole IVOST to all acute hospitals in NHSGGC, the largest acute health board in Scotland, and measure the impact on AS, drug costs, nursing workload and environmental sustainability. Methods A QI scale and spread approach was used including the following. Eye catching posters displayed in key ward areas/electronic guideline platform. Electronic prescribing (HEPMA) IVOST prompts displayed when prescribing or administering IV metronidazole. ‘Think tabs before jags’ blog7 was used to highlight the initiative widely. HEPMA targeted prospective audit/feedback and antimicrobial ward round review of patients prescribed IV metronidazole. Multidisciplinary staff champions and Antibiotic Guardian ‘Gold Star’ awards were used to promote staff engagement. Regular feedback to medical, nursing and pharmacy teams via update reports and hospital governance committees. Oral and IV metronidazole usage data was calculated at baseline and for 40 months ‘post change’. Improvement measures in terms of reduced IV administrations, drug costs and nursing time saved8 were calculated. Plastic waste reduction (giving sets, single use plastics, cannula, safety needles, gloves and aprons) associated with IVOST was calculated in terms of carbon dioxide equivalent (CO2e) emissions using a hybrid carbon foot-printing methodology and emissions factor databases.9 Results A 33% median reduction in total (IV plus oral) metronidazole defined daily doses (DDDs) per 1000 occupied bed days (OBDs) (Figure 1). A 46% median reduction in IV metronidazole DDDs/1000 OBDs (Figure 2), equating to 5250 and 63 000 fewer IV administrations monthly and annually, respectively. Equivalent nursing time saved equating to 1750 h per month and 21 000 h per year. A 37% (£60 000) annual reduction in metronidazole drug cost. The carbon footprint saving achieved from metronidazole IVOST was calculated as 1.48111 KgCO2e per dose equating to 7775 KgCO2e per month and an annual carbon footprint saving of 93.3 tonnes CO2e. Conclusions A QI scale and spread approach, to raise awareness of the multidisciplinary team to the high oral bioavailability of metronidazole and benefits of appropriate IVOST, resulted in a change in prescribing behaviour and a significant reduction in IV administrations. The initiative also resulted in a sustained reduction in total metronidazole use across NHSGGC acute hospitals. This is important in terms of improved AS, patient safety, workforce cost and efficiency and environmental sustainability. Crucially these results support attainment of national targets for tackling AMR5 and the climate emergency.6 Figure 1.Total metronidazole (IV+ oral) DDDs per 1000 OBDs. Figure 2.IV metronidazole and oral metronidazole DDDs per 1000 OBDs.

Abstract Background Antimicrobial stewardship (AS) quality improvement (QI) initiatives promoting IV to oral switch (IVOST)1 or reduced IV dosing frequency provide benefits for patients, staff and the environment.2,3 To determine if initiatives are effective, we need to measure if improvement has occurred. Measuring carbon-footprint savings can be challenging due to lack of available information on the environmental impact of pharmaceutical products and the time needed to complete a thorough environment impact calculation. Consequently, more pragmatic ‘good enough’ QI indicator measures need to be developed to enable improvement in the environmental impact of QI initiatives promoting reduced IV use to be more easily measured and compared.4 One such approach would be to remove drug and reconstitution products from the calculation5 and focus on the equipment commonalities used in the standard process of peripheral IV administration. This approach enables standardized indicator measures for carbon-footprint savings in terms of plastic waste reduction to be developed. Objectives To measure the carbon-footprint saving associated with switching from peripheral IV to solid oral administration in terms of plastic waste reduction and use this to develop standard indicator measures for calculating carbon-footprint savings associated with IVOST or reduced IV dosing frequency. Methods Using process mapping the core administration equipment for common peripheral IV dosing schedules was collated over a 72 h period in line with local policy for replacement of peripheral lines. A hybrid carbon foot-printing methodology was used to estimate the carbon-footprint of peripheral IV and oral medicine administration in terms of carbon dioxide equivalent (CO2e) emissions.6,7 Emissions associated with the IV and oral pharmaceutical products were excluded. A process-based approach was used to estimate emissions of the syringe, cannula, safety needle and oral medicine plastic pot using emission factors taken from the UK government carbon conversion factors database6. In addition, an environmentally extended input output analysis (EEIOA) was used to estimate the emissions associated with alcohol wipes, saline solution, IV3000, Octopus 2 and Volumat Line using the medical instrument conversion factor taken from the 20/21 Greener NHS database. Emissions associated with non-sterile gloves and aprons were taken from a previously published report7. Results This pragmatic approach enabled CO2e savings in terms of plastic waste reduction for IVOST of common IV dosing schedules to be calculated irrespective of the drug administered (Table 1). This methodology also enabled CO2e savings to be calculated and compared between different drugs when switching from IV to oral administration at the same/different dosing frequency or when switching from higher frequency (e.g. 4-6 times daily) to lower frequency (once or twice daily) IV regimens (Tables 1 and 2) or to extended interval IV regimens given weekly or monthly. Conclusions Taking a pragmatic ‘good enough’ approach to measuring improvement in carbon-footprint savings associated with IVOST enabled standard indicator CO2e savings in terms of plastic waste reduction to be calculated. This is important in supporting more efficient, straightforward and comparable measurement of carbon-footprint savings from AS QI initiatives promoting IVOST or switching from higher to lower frequency dosing schedules of different drugs. Table 1.Comparison of the carbon footprint of common peripheral IV dosing schedules and savings of IVOST in terms of plastic waste reductionAdministration scheduleIVKgCO2e per doseOralKgCO2e per doseKgC02e saving per IVOST doseKgCO2e saving per IVOST dayOnce daily dosing1.62350.00671.61681.6168Twice daily dosing1.41560.00671.40892.8178Three times daily dosing1.34680.00671.34014.0203Four times daily dosing1.31220.00671.30555.2220Six times daily dosing1.27770.00671.27107.6260Calculations exclude drug and reconstitution products. Table 2.Examples of comparison of the carbon footprint savings in terms of plastic waste reduction of peripheral IVOST of different dosing frequency regimens or reducing IV dosing frequencyChange in administration regimenKgCO2e saving per daySix times daily IV flucloxacillin switched to ONCE daily IV daptomycin6.0427 (1.2777 × 6) − 1.6235Twice daily IV vancomycin switched to BD oral linezolid2.8178 (1.4156 × 2) − (0.0067 × 2)Four times daily piperacillin/tazobactam switched to TDS oral co-amoxiclav5.2287 (1.3122 × 4) − (0.0067 × 3)Three times daily IV meropenem switched to ONCE daily IV ertapenem2.4169 (1.3468 × 3) − (1.6235)Calculations exclude drug and reconstitution products.

Objectives: Low tidal volume ventilation (LTVV) is a ventilatory strategy with the advantages of minimizing diaphragm movements and reducing hypercapnia and barotrauma risks. This preliminary study aims to report on the safety and effectiveness of LTVV applied during percutaneous US-guided liver ablations of focal malignancies. Methods: Patients affected by focal liver malignancies treated with percutaneous microwaves ablation were retrospectively included in this single-center analysis. Arterial gas analysis was performed immediately before and after ablation to evaluate the arterial pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), and plasma lactate levels. The primary endpoint of this study was to evaluate the safety and efficacy of LTVV during percutaneous liver cancer ablation. The secondary endpoint was to assess the procedural technical success in terms of correct needle probe targeting without the need for repositioning. Results: Ten patients affected by a single liver lesion had been analyzed. The ASA score was three in all patients, with three patients also suffering from COPD. The procedural technical success was 100%: ablations were performed with a single liver puncture without the need for changing access or repositioning the needle. No variations in post-ablation arterial gas analysis requiring anesthesiological management remodulation occurred. Lactate levels remained stable and hemodynamic balance was preserved during all procedures. No switch to standard volume ventilation was required. Conclusions: In this preliminary study, LTVV was a safe and effective anesthesiological protocol in patients treated with percutaneous ablations of liver malignancies, offering an ideal balance between patient safety and percutaneous needle probe positioning precision. Larger prospective studies are needed to confirm these findings.

THU-264 Safety and pharmacokinetics of bepirovirsen, delivered subcutaneously by vial, or prefilled syringe fitted with a safety syringe device in healthy adult participants, and syringe device ease of use: a randomised phase 1 trial

IntroductionBimekizumab has a favourable safety profile and has demonstrated rapid and superior efficacy, compared with placebo, adalimumab, ustekinumab, and secukinumab, in treating psoriasis. A previous study demonstrated the safe and effective subcutaneous self-injection of 320 mg bimekizumab via two 1 mL (2 × 160 mg) doses using safety syringe (SSy) or auto-injector (AI) devices. Delivery of 320 mg bimekizumab via a single 2 mL self-injection could lead to an improved treatment experience for patients.MethodsWe describe the results from four studies. Two self-injection experience studies (DV0002 [n = 38] and DV0006 [n = 89], sub-studies of the phase 3 study BE BRIGHT [NCT03598790]) assessed the safe and effective self-administration of bimekizumab at week 8 and baseline, as well as patient self-injection experience and pain, in patients with moderate to severe plaque psoriasis using the 2 mL SSy or AI. Additionally, we report on two bioequivalence studies (UP0068 [n = 71] and UP0119 [n = 121]) that describe pharmacokinetic profiles for two 1 mL injections and a single 2 mL injection, delivered by SSy or AI devices in healthy participants.ResultsAll patients were able to administer safe and effective self-injections at baseline and week 8 using the different 2 mL devices, except one patient that administered an incomplete dose as a result of injection site pain that was mild. Overall, bimekizumab was generally well tolerated and all adverse device effects reported were mild and did not lead to discontinuation. Patients reported a positive self-injection experience with low pain scores (all ≤ 12.0/100). Bioequivalence was demonstrated for bimekizumab between a single 2 mL injection and two 1 mL injections, using both the SSy and AI.ConclusionThe 2 mL SSy and AI devices offer patients with moderate to severe plaque psoriasis two different safe and effective options for the delivery of bimekizumab, empowering individuals to select a device on the basis of personal preference.Graphical abstract available for this article.Trial RegistrationClinicalTrials.gov identifier, NCT03766685.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-025-01366-6.

ISMP warns of risk of injury with prefilled syringes packaged without needle safety guards.

This Phase I, randomized, multicenter, open-label, parallel-group, single-dose study assessed the relative bioavailability of the anti-interleukin-5 antibody depemokimab (100mg) when administered subcutaneously via either a safety syringe device (SSD) or an autoinjector (AI). Healthy adult participants were randomized I:I to SSD or AI treatment arms and I:I:I to the injection site (upper arm, abdomen, or thigh). Participants were followed up for 30 weeks; blood samples were collected for pharmacokinetic (PK) assessment before dosing on Day 1 and up to Week 26. Depemokimab concentration profile as measured by plasma maximum concentration (Cmax), the area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf), PK parameters, immunogenicity, and safety were assessed. Overall, 140 participants were enrolled (n=70 per arm). Mean plasma concentration-time profiles of depemokimab were similar in both treatment arms, regardless of the injection site, adjusted geometric mean AI:SSD ratios for Cmax and AUC0-inf were 1.03 and 1.03, respectively, with all 90% confidence intervals within the bioequivalence bounds of 0.80-1.25. PK parameters were comparable across treatment arms. Treatment-related adverse events were reported in 19% of SSD and 20% of AI participants, with headache being the most common across both arms; no adverse events led to study withdrawal. These results support the use of either SSD or AI for subcutaneous administration of depemokimab.

Therapeutic monoclonal antibody (mAb) drug products are increasingly used to treat both chronic and acute diseases. These mAb drug products are often developed for subcutaneous (SC) injection to simplify dosing compared with intravenous (IV) infusion. For SC injection, the mAb liquid drug product is typically filled in a vial for use with a syringe or in a prefilled syringe, which can then be assembled into a safety syringe device or an autoinjector for direct administration. A placebo is an inert formulation (one without an active ingredient) that lacks pharmacological activity or a therapeutic effect. It serves as a control in blinded clinical trials to evaluate the efficacy of a new treatment. A suitable blinding/matching/masking strategy is crucial to ensure that study participants cannot distinguish between the active mAb formulation and the placebo. The success of these strategies is pivotal in ensuring the accuracy and reliability of clinical trial results. This Review summarizes recent advances and key considerations related to placebo strategies. It covers the benefits and challenges of SC injection of therapeutic mAbs compared to IV infusion, the placebo effect, the significance of blinding/matching/masking, and various strategies. Strategies discussed include the use of traditional placebos (e.g., normal saline, 5% w/v dextrose solution, and formulation buffer of the active mAb), syringe blinding, the use of different gauge syringe needles, novel (custom) placebos, dilution, independent administration, and multiple injections. Additional topics covered include the incidence of antidrug antibodies (ADAs), the benefits and challenges associated with different strategies, and regulatory expectations regarding custom placebos. By addressing these critical aspects, the Review aims to contribute to the growing body of knowledge and ongoing efforts to enhance the effectiveness of formulation blinding, matching, and masking in clinical trials.

A rare esophageal foreign body found in a patient with mental retardation: safety needle

BackgroundKidney biopsy is crucial for diagnosing kidney diseases but involves risks, notably bleeding, which must be balanced with diagnostic precision. This study examines the effect of the biopsy needle’s cortical tangential angle and depth on specimen adequacy and safety outcomes.MethodsThis single-center, retrospective study reviewed electronic medical records from kidney biopsies performed between January 1, 2016 and December 31, 2020. Included were patients undergoing real-time ultrasound-guided percutaneous kidney biopsies. Exclusion criteria were pediatric patients, renal mass or transplant biopsies, and cases with incomplete records. Primary variables included biopsy needle cortical tangential angle and depth. Outcomes were tissue adequacy and safety, with complications assessed within 24 h.ResultsOut of 443 biopsies performed, 124 met the inclusion criteria. Our patient population had a mean BMI of 27.17 kg/m2, which met the criteria for obesity based on BMI standards for Asians, and they also had relatively small kidneys (< 9 cm) with parenchymal thinning. Biopsies at angles of 30°–60° yielded more glomeruli (12 vs. 5, p < 0.001) and had a higher pathologist-reported adequacy (82.67% vs. 59.18%, p = 0.004). Needle depth did not significantly impact adequacy. Major complications occurred in 12.90% of cases, with blood transfusions required in 8.06% and embolizations in 3.23%. All technical factors lost statistical significance after adjusting for confounders, except for increased echogenicity, which remained significant.ConclusionsThe optimal needle angle for kidney biopsies is 30°–60° for the highest diagnostic yield compared to angles < 30° or > 60°. Our study did not reveal statistically significant differences in major complications between these angle ranges. This greater understanding of the relationship between biopsy angle, needle trajectory depth, and diagnostic and safety outcomes offers valuable insights for optimizing kidney biopsy procedures.Graphical

Evaluation of Pharmacokinetics of Lebrikizumab in Healthy Individuals After Subcutaneous Administration Using a Prefilled Syringe or Autoinjector in a Phase 1 Randomized Study