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Purpose To evaluate the clinical effect of the warming step for subcutaneous (SC) injection on injection site pain (ISP). Methods A single center, randomized, partially blinded, crossover study in 44 healthy participants was conducted. Participants self-injected with autoinjectors (1 mL) with either high pain (citrate/sodium chloride (NaCl)) or low pain (mannitol) formulations at refrigerated temperature or warmed to room temperature (RT) according to the instructions for use (IFU). The ISP was recorded using visual analog scale (VAS) and injection site reactions (ISRs) were captured using severity scores. Results The average VAS scores were clinically different between high pain and low pain formulation but not affected by the warming step. While the average VAS was not affected by injectate temperature, some individual participants reported bidirectional VAS responses to injectate temperature. A post injection questionnaire showed that most participants were not bothered by the cold sensation of the injected solution. The clinical results are consistent with modeling that indicates rapid temperature equilibration of subcutaneously injected solutions. Conclusion Formulation composition was the dominating factor contributing to ISP as compared to solution temperature due to transient thermal equilibrium of the injected solution in SC tissue. While injection temperature may be a lever for improving the injection experience for some patients, the warming step is unlikely to reduce ISP for most patients. Although this study was conducted with 1 mL injection of two representative formulations, this finding of lack of correlation between ISP and solution temperature is likely extrapolatable to most small volume (e.g., ≤ 2 mL) injections of subcutaneous formulations.

Abstract This article reviews the literature and the authors’ experiences regarding the performance of lower extremity fluoroscopically guided procedures from the hip to the toes. An overview of injections and aspirations, their indications, risks, and complications are provided, focusing on anesthetics, corticosteroids, and contrast agents. A variety of approaches to each joint and the associated pearls and pitfalls of each approach will be discussed.

In this randomized, controlled trial involving women in South Africa and Uganda, twice-yearly subcutaneous lenacapavir was superior to daily oral emtricitabine–tenofovir disoproxil fumarate in preventing HIV infection.

Background Polynucleotide (PN) filler often causes pain and can lead to delivery inaccuracies when applied via intradermal injection using a traditional needle. Aims To evaluate the efficacy of treatment and the pain during the procedure using conventional needle injection versus a needle‐free jet system for intradermal PN filler application. Methods In this split‐face clinical trial, 10 Korean subjects were enrolled. Each subject received an intradermal injection of PN filler on one side of the face and a needle‐free jet injection using CureJet on the other side. Assessments included global and 3D skin imaging at each visit. Pain intensity was evaluated using visual analogue scale (VAS) scores during the injection. Additionally, patient satisfaction and adverse events were documented. Results Findings revealed that Global Aesthetic Improvement Scale scores and patient satisfaction were significantly higher with the CureJet compared to the needle injection method. VAS scores were notably lower on the CureJet side. Improvements in both pore and wrinkle indices were observed from baseline, with a more pronounced improvement rate on the CureJet side compared to the needle injection side. Conclusions Needle‐free injection of PN for aging skin was found to be effective in enhancing pore and wrinkle improvement, while reducing associated discomfort.

PurposeThe objective of this work was to systematically evaluate the effects of formulation composition on subcutaneous injection site pain (ISP) using matrices comprising of common pharmaceutical excipients.MethodsTwo randomized, blinded, crossover studies in healthy subjects were conducted at a single site, where subjects received 1 mL SC injections of the buffer matrices. ISP intensity was measured using a 100 mm visual analogue scale (VAS), which was then analyzed via heatmap, categorical grouping, subgroup analysis, and paired delta analysis.ResultsBuffer type, buffer concentration and tonicity agent showed a substantial impact on ISP. Citrate buffer demonstrated a higher ISP than acetate buffer or saline). The 20 mM citrate buffer was more painful than 10 or 5 mM citrate buffers. NaCl and propylene glycol were significantly more painful than sugar alcohols (mannitol, sucrose, trehalose or glycerol). Histidine buffers exhibited ISP in the descending order of 150 mM > 75 mM > 25 mM > 0 mM NaCl, while histidine buffers containing Arginine-HCl at 0, 50, or 150 mM all showed very low ISP. Histidine buffer at pH 6.5 showed a lower ISP than pH 5.7.ConclusionsThis systematic study via orthogonal analyses demonstrated that subcutaneous ISP is significantly influenced by solution composition.

An investigational wearable injector (WI), the BD Libertas Wearable Injector (BD Libertas is a trademark of Becton, Dickinson and Company), was evaluated in an early feasibility clinical study for functional performance, tissue effects, subject tolerability, and acceptability of 5 mL, non‐Newtonian ~ 8 cP subcutaneous placebo injections in 52 healthy adult subjects of 2 age groups (18–64 years and ≥ 65 years). Randomized WI subcutaneous injections (n = 208, 4/subject) were delivered to the right and left abdomen and thigh of each subject, 50% (1 thigh and 1 abdomen) with a defined movement sequence during injection. Injector functional performance was documented. Deposition was qualified and quantified with ultrasound. Tissue effects and tolerability (pain) were monitored through 24 hours with corresponding acceptability questionnaires administered through 72 hours. WI (n = 205) automatically inserted the needle, delivered 5 mL ± 5% in 5.42 minutes (SD 0.74) and retracted. Depots were entirely (93.2%) or predominantly (5.4%) localized within the target subcutaneous tissue. Slight to moderate wheals (63.9%) and erythema (75.1%) were observed with ≥ 50% resolution within 30–60 minutes. Subject pain (100 mm Visual Analog Scale) peaked mid‐injection (mean 9.1 mm, SD 13.4) and rapidly resolved within 30 minutes (mean 0.4 mm, SD 2.6). Subjects’ peak pain (≥ 90.2%), injection site appearance (≥ 92.2%) and injector wear, size, and removal (≥ 92.1%) were acceptable (Likert responses) with 100% likely to use the injector if prescribed. Injection site preference was divided between none (46%), abdomen (25%), or thigh (26.9%). The investigational WI successfully delivered 5 mL viscous subcutaneous injections. Tissue effects and pain were transient, well‐tolerated and acceptable. Neither injection site, movement or subject age affected injector functional performance or subject pain and acceptability.

Induced seismicity associated with fluid injection has raised serious concerns for the safety and efficiency of geo-energy systems. Cyclic injection has recently been proposed as an alternative injection scheme to reduce the large magnitude injection-induced seismicity. However, the influence of cyclic injection on the activation of natural fractures in granite and the resulting seismic risk is not yet clear. This study investigates the injection-induced activation of a critically stressed natural fracture in a granite core sample, particularly focusing on the comparison between monotonic and cyclic water injection under pressure-controlled and volume-controlled conditions. Experimental results show that the acceleration and deceleration of fracture slip are modulated by the shear stress imbalance between the fixed shear stress and the evolving frictional strength of the fracture. Fracture slip affects the fluid pressure distribution on the fracture, which in turn regulates the frictional strength of the fracture. At a small total shear displacement (i.e., ~ 0.9 mm in this study), cyclic injection with a restricted peak injection pressure results in aseismic fracture slip at much smaller peak slip rates compared to that during the monotonic injection. On the one hand, the more uniform reduction in effective normal stress caused by cyclic injection encourages slow and stable fracture slip, characterized by the smaller peak slip rates. On the other hand, the flowback of injected fluid or suspension of injection could prevent the occurrence of fast-accelerated fracture slip during cyclic injection. However, the fracture can become unstable when it has experienced a considerable amount of total shear displacement (larger than ~ 0.9 mm in this study), and likely gained a significantly enhanced permeability. Continued injection after the unstable shut-in stage, signified by an unusual increase in slip rate and an accelerated drop in injection pressure, could result in rapid and unstable fracture slip.

PurposeTo evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects.MethodsA single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness. A syringe pump was used to study the effect of different volumes (5, 12, 25 mL) of a viscous placebo solution and needle lengths (6, 9 and 12 mm) delivered at 0.5 mL/min.ResultsAcross all treatments, injection sites were observed to have negligible leakage, ~34 kPa of back pressure, and VAS of mild pain with higher pain from needle insertion than during injection. While mild to moderate erythema was the most frequently reported ISR and edema was most prominent for 25 mL injections, all ISRs were resolved within 4 hours post injection. Subjects were unbothered by ISRs across all treatments and rated them as low distress scores (average 1.0–1.5 out of 6).ConclusionSC injection of 25 mL is feasible and tolerable using a low-pain formulation for abdomen injection irrespective of subcutaneous thickness and injection depths at a delivery rate of 0.5 mL/min.

BACKGROUND: Epidural injection (EI) has been used to manage lower back and radicular leg pain caused by a herniated lumbar disc. There are 3 types of EI techniques currently being used: transforaminal (TFEI), interlaminar (ILEI), and caudal epidural injections (CEI). OBJECTIVES: To evaluate the comparative effectiveness of TFEI, ILEI, and CEI in reducing pain and improving function in patients with HLD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, and Scopus databases were searched from the earliest records up to August 2022 for randomized controlled trials (RCTs) and non-RCTs. The standard mean differences (SMDs) in the changes in the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores were calculated from one week through one month posttreatment (short-term) and from 4 months through 6 months posttreatment (long-term). RESULTS: In total, 11 studies comprising 1,050 patients were included. Network meta-analysis showed that the improvement in the VAS scores was better with TFEI than with CEI (SMD = -1.16, 95% CI = -2.10 to -0.23). Ranking probability analysis showed that TFEI had the highest probability of being the best treatment for reducing pain and improving function in the short- and long-term evaluation periods. LIMITATIONS: Only a small number of previous studies were included in our analysis. Also, subgroup analysis according to the injection volume, material type, or pain onset could not be conducted. CONCLUSIONS: TFEI had the best potential of the 3 EI techniques to reduce pain and improve function in patients with a herniated lumbar disc. Further qualified trials comparing the effects of these 3 techniques are warranted to derive definitive conclusions. KEY WORDS: Disc herniation, back pain, radicular pain, epidural injection, transforaminal injection, interlaminar injection, caudal injection, lumbar spine

Controlling fluid injection is widely considered a key to limiting the size of injection‐induced seismicity, yet whether and how it limits earthquake size remains debated. We perform injection‐reactivation experiments on critically stressed faults to test how different injection strategies shape slip and seismic moment release. We find that injection strategies regulate the cadence of slip events rather than the total seismic moment. Compared to continuous injection, cycled injection triggers frequent and smaller events, reducing maximum moment magnitude and deformation energy of individual events. Injection–extraction cycles actively reduce pore pressure, temporally partition successive slip events, and effectively suppress delayed seismicity. Regardless of constant or cycled injection rates, maximum seismic moment (M0 ${M}_{0}$) scales with cumulative injection volume (ΔV ${\\Delta }V$) i.e.,M0∝ΔV3/2 $\\left(\\mathrm{i}.\\mathrm{e}.,{M}_{0}\\propto {\\Delta }{V}^{3/2}\\right)$. Our laboratory results suggest that regulating the cadence of moment release promotes effective hazard mitigation.