Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance.

AIM: The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC) injection pain tolerance. METHODS: The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8-10, and 15-20 cP) combined with two different injection flow rates (0.02 and 0.3 mL/s). All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS) (0 mm/no pain, 100 mm/extreme pain). The location and depth of the injected fluid was assessed through 2D ultrasound echography images. RESULTS: Viscosity levels had significant impact on perceived injection pain (P=0.0003). Specifically, less pain was associated with high viscosity (VAS =12.6 mm) than medium (VAS =16.6 mm) or low (VAS =22.1 mm) viscosities, with a significant difference between high and low viscosities (P=0.0002). Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89). Slow (0.02 mL/s) or fast (0.30 mL/s) injection rates also showed no significant impact on perceived pain during SC injection (P=0.79). In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. CONCLUSION: The results of this study suggest that solutions of up to 3 mL and up to 15-20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High viscosity injections were shown to be the most tolerated, whereas injection volume and flow rates did not impact perceived pain.

Results of a human factors experiment of the usability and patient acceptance of a new autoinjector in patients with rheumatoid arthritis.

PURPOSE: This study evaluated the human factors affecting the ease of use of a disposable autoinjector developed for subcutaneous self-injections performed by patients with chronic diseases. MATERIALS AND METHODS: This was a randomized, single-center study conducted with 65 patients with rheumatoid arthritis. Patients performed six simulated injections. Assessments of patient device acceptance and device usability were made by patient reports and independent observations of compliance with the device instruction for use (IFU) following single injections and repeated injections. RESULTS: A total of 390 simulated injections were performed. Patient device acceptance was high; more than 90% of patients found each of the tested criteria to be acceptable (>80% was required for statistical significance; P<0.016). Perceived ease of use and simplicity of the three-step process resulted in high acceptance scores: mean scores (± standard deviation) were 8.71 (±1.18) and 8.05 (±0.37), respectively, on a 0-10-point scale. Patients also expressed their acceptance with the ease and usefulness of the detection of the remaining drug in the autoinjector. In addition, 80% of patients declared that they would recommend the device to someone else. Globally, the human factors tested (age, sex, hand disability [Cochin score], extent of previous experience with self-injection [ie, expert or naïve]) had no impact on IFU device compliance. In particular, the lack of a Cochin score interaction indicated that the degree of hand disability is not a predictive factor of poor self-injection capability with this autoinjector. CONCLUSION: This study demonstrated a high level of patient acceptance for self-injection with this autoinjector among patients with rheumatoid arthritis. In particular, patients with severe hand disability were able to successfully comply with device IFU.

Echographic measurement of skin thickness in sites suitable for intradermal vaccine injection in infants and children.

Whereas the knowledge of skin thickness is essential to determine microneedle length and ensure proper administration of and better responses to intradermal vaccines, very few figures are available, especially in infants and children. Using ultrasound echography, we investigated skin thickness in 384 children aged 4-7, 12-18, and 54-66 months at potential body sites for intradermal vaccine delivery: deltoid, suprascapular, upper back, and lumbar area. The mean epidermis plus dermis thickness was significantly higher at the suprascapular than at the deltoid site (1.29mm vs. 1.22mm) and remained relatively unchanged whatever the BMI, age, sex, and skin phototype. In the 43 children aged 54-66 months, the mean skin thickness was significantly higher in the upper than in the lumbar area (1.39mm vs. 1.31mm). In this study setting, the heterogeneity in skin thickness cannot be considered sufficient to indicate various microneedle lengths for various ages or injection sites.

Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers.

OBJECTIVE: A disposable autoinjector was developed for subcutaneous (SC) self-injection by patients with chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections performed by nurses using a syringe. METHODS: This was a randomized, single-center, crossover study comparing SC self-injection using an autoinjector with SC nurse-administered injection using a syringe. Two volumes (0.2 mL and 1 mL) were injected into healthy volunteers. Study objectives included assessment of the accuracy and consistency of the volume injected by the injection systems, and skin reaction and pain associated with the injection. The fluid depot in the SC tissue layer was evaluated by ultrasound. Subject acceptance was evaluated using questionnaires on attitudes and emotions towards the injection technique, and challenged by seeking the subjects' preferred system for a final study injection or future treatment. RESULTS: A total of 960 injections (480 with autoinjector, 480 with syringe) were performed in 40 subjects. There were no significant differences in mean fluid leakage and injected volumes between the systems. Pain associated with the injection was significantly lower with the auto-injector than with the syringe. Local skin reaction at the injection site was overall satisfactory. Injections were appropriately performed by all subjects. At study end, all 40 subjects preferred the autoinjector for a final study injection and for future treatment. CONCLUSION: This study indicated that the autoinjector used by the subject was similar to a syringe used by a nurse in terms of performance and safety in administering the injections, and better in terms of pain, overall acceptance, and preference.

Antidepressant response and fluvoxamine plasma concentrations: a pilot study.

The objective of this pilot study was to examine the relation between fluvoxamine (FVX) plasma concentrations, therapeutic response and side effects during a four-week treatment period. Twenty-two patients who met the DSM-IV criteria for major depression received 100 mg FVX during the first 2 days of treatment and then 150 or 200 mg/day. No clear relationship between plasma concentrations and side effects was detectable. A relationship between plasma concentrations and clinical efficacy was detectable after 21 days but not after 28 days of treatment. These preliminary results indicate that therapeutic drug monitoring might be useful for patients treated with FVX.