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Clinical evaluation of large volume subcutaneous injection tissue effects, pain, and acceptability in healthy adults.

ABSTRACT: Determining feasibility and tolerability of large volume viscous subcutaneous injection may enable optimized, intuitive delivery system design. A translational early feasibility clinical study examined large volume subcutaneous injection viability, tolerability, acceptability, tissue effects and depot location for ~1, 8, and 20 cP injections at volumes up to 10 ml in the abdomen and 5 ml in the thigh in 32 healthy adult subjects. A commercial syringe pump system delivered 192 randomized, constant rate (20 µl/s) injections (6/subject) with in-line injection pressure captured versus time. Deposition location was qualified via ultrasound. Tissue effects and pain tolerability were monitored through 2 hours post-injection with corresponding Likert acceptability questionnaires administered through 72 hours. All injection conditions were feasible and well-tolerated with ≥79.3% favorable subject responses for injection site appearance and sensation immediately post-injection, increasing to ≥96.8% at 24 hours. Mean subject pain measured via 100 mm visual analog scale increased at needle insertion (6.9 mm, SD 10.8), peaked during injection (26.9 mm, SD 21.7) and diminished within 10 minutes post-removal (1.9 mm, SD 4.2). Immediate injection site wheal (90.9%) and erythema (92.6%) formation was observed with progressive although incomplete resolution through 2 hours (44.6% and 11.4% remaining, respectively). Wheal resolution occurred more rapidly at lower viscosities. Most subjects (64.5%) had no preference between abdomen and thigh. Correlations between tissue effects, injection pressure and pain were weak (Pearson's rho ± 0-0.4). The large volume injections tested, 1-20 cP viscosities up to 10 ml in the abdomen and 5 ml in the thigh, are feasible with good subject acceptability and rapid resolution of tissue effects and pain.

SUBMITTER: Woodley WD

PROVIDER: S-EPMC8742644 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectiveThis study was performed in healthy Chinese subjects to evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of a novel injection formulation of dexlansoprazole in the context of single and multiple administration, compared with the original lansoprazole injection.MethodsHelicobacter pylori-negative healthy volunteers were recruited, and 70 participants were enrolled into five dosing groups (seven males and seven females in each group), including 15 mg once daily (qd), 15 mg every 12 h (q12h), 30 mg qd and 30 mg q12h of dexlansoprazole treatment for 5 days, as well as 30 mg q12h of lansoprazole treatment for 5 days. Blood samples were collected at scheduled time spots postdose on day 1 (first dose) and day 5 (last dose). Twenty-four-hour intragastric pH was continuously monitored on day 0 (baseline) and days 1 and 5. Dexlansoprazole and S-lansoprazole in human plasma were determined by validated chiral liquid chromatography with tandem mass spectrometry, and the pharmacokinetic parameters were determined by a non-compartmental method using Phoenix WinNonlin software. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events.ResultsThe half-life (t½) and clearance (CL) of dexlansoprazole were 1.76-2.06 h and 4.52-5.40 L/h, respectively, while the t½ and CL of S-lansoprazole were 0.87-1.02 h and 34.66-35.98 L/h, respectively. No drug accumulation after repeated administration was noted. Administration of lansoprazole 30 mg resulted in higher area under the concentration-time curve from time zero to the last measurable concentration (AUCt) of dexlansoprazole than that of dexlansoprazole 15 mg (p = 0.026). Zero to 24 h after q12h multiple dosing, median and mean intragastric pH, percentage of time with the intragastric pH above 4.0 [TpH ≥ 4.0(%)] and percentage of time with the intragastric pH above 6.0 [TpH ≥ 6.0(%)] in the dexlansoprazole 15 mg q12h group were 6.07 ± 0.61, 5.70 ± 0.76, 83.58 ± 12.34, and 53.70 ± 17.06, respectively, which was similar to the lansoprazole 30 mg q12h group, i.e. 6.15 ± 0.62, 5.88 ± 0.67, 87.26 ± 12.08 and 57.00 ± 16.35, respectively. A weak positive correlation between dexlansoprazole AUCt and baseline-adjusted TpH ≥ 4.0(%) over 0-24 h was observed, with Pearson correlation coefficients of 0.437 (p = 0.029), while no correlation was observed between AUCt and baseline-adjusted TpH ≥ 6.0(%) over 0-24 h.ConclusionEvery 12 h intravenous dosing of dexlansoprazole up to 30 mg for 5 days was safe and well-tolerated in healthy Chinese subjects. Every 12 h dosing of dexlansoprazole 15 mg has a comparable effect of gastric acid inhibition as lansoprazole 30 mg q12h.Trial registrationClinicalTrials.gov ID NCT03120273.

Project description:IntroductionStress cardiomyopathy, also known as takotsubo syndrome, is characterized by transient left ventricular dysfunction not attributable to obstructive epicardial coronary artery disease. Several pathological mechanisms have been proposed, including multivessel coronary artery vasospasm, coronary microcirculatory dysfunction, and excess catecholamine secretion.Case presentationA 68-year-old male presented to our institution for elective surgical removal of a cutaneous basal cell carcinoma on the right side of his face. Within minutes following the administration of local anaesthesia, the patient developed severe hypertension, tachycardia, ST-segment elevation on the electrocardiogram, and non-sustained broad-complex tachycardia. Urgent cardiac catheterization revealed non-obstructive coronary artery disease and left ventriculography demonstrated apical hypokinesia and moderate systolic dysfunction consistent with the takotsubo syndrome. On review of the medications administered, it was noted that an unintentionally large dose of adrenaline (4mg) had been injected subcutaneously with lignocaine. He was monitored in the coronary care and recovered fully with supportive care only. Bisoprolol was initiated on day 1 post procedure. On follow-up one month later, his left ventricular function had normalized.DiscussionOur case report provides direct evidence supporting the pathogenetic role of excess catecholamine secretion in the development of the takotsubo syndrome. A review of the literature reveals that both exogenous catecholamine administration (adrenaline injection in the context of anaphylaxis or infiltrative anaesthesia) and excess endogenous catecholamine (phaechromocytoma) secretion has been associated with the takotsubo syndrome. Local infiltrative anaesthesia with the addition of adrenaline is commonly used as a vasoconstrictor in a wide variety of surgical procedures. To reduce the risk of adverse events, the lowest effective concentration of adrenaline to provide pain control and vasoconstriction is recommended.

Project description:AimTo prospectively assess toxicities of curative-intent intensity-modulated conformal radiotherapy (IMRT) in patients with extremity soft tissue sarcomas (ESTS).MethodsData from 59 consecutive patients with ESTS between 2014 and 2019 were both retrospectively and prospectively analysed. Toxicity data were collected both by confidential mailed survey (39% completed) and medical charts, and graded according to CTCAE v5.0. Normal tissues dosimetric data (healthy soft tissue segment, joint and bone) were included. The healthy soft tissue segment was created by adding 5 cm on either side of the PTV on CT axial slices, the PTV and bone (and articulation if present) were then removed from the generated volume.ResultsIMRT was delivered post-operatively for nearly half of patients (n = 24, 41%), preoperatively for 18 (31%) and exclusively for 17 (28%; salvage: 13% or immediately inoperable: 15%). The median total dose delivered to the planned target volume (PTV) was 50.4 Gy (36-68 Gy) and 13 patients (22%) received a boost. With a median follow-up of 27 months (6-94 months), a total of 87 late effects were identified in 44/59 (75%) patients: 89% G1-2, and 11% G3-4. The main G1-2 toxicities were: functional limitation (36%), oedema (29%), gait disorders (20%), neurological disorders (20%) and chronic pain (32%). G3-4 toxicities were pain (n = 2), arterial stricture (n = 1) and a chronic wound requiring skin graft (n = 2). No bone fracture was observed. Quality of life was rated as good or very good in 70% patients who completed the survey. Larger (>3500 cm3) healthy soft tissue segment volume was associated with decreased late toxicities (p = 0.02). No other predictive factor of toxicity was identified. The 2-year rates of local control, overall survival and recurrence-free survival were 90%, 90% and 64%, respectively.ConclusionHealthy soft tissue segment volume influenced toxicity. Long-term prospective monitoring in a homogeneous population remains critical to assess the impact of IMRT induced chronic toxicity in ESTS patients. This should ideally lead to a validated normal tissue dose constraint (e.g.: healthy soft tissue segment volume > 3500 cm3) to recommend for practitioners to help reduce the late toxicity risk.

Project description:ObjectivesExpanding contraceptive options through self-injection may improve access and confidentiality. There are few published studies on contraceptive self-injection in sub-Saharan Africa and none in West Africa, a region with high unmet need. This study was performed to assess feasibility of subcutaneous DMPA self-injection in Senegal; objectives were to (1) measure the proportion of participants who self-injected competently 3 months after training, (2) measure the proportion who self-injected on time (defined conservatively as within 7 days of reinjection date), and (3) assess acceptability of self-injection.Study designIn this prospective cohort study, 378 women aged 18-49 years were trained to self-inject by study nurses. Three months later, women returned unprompted to the clinic to self-inject, and technique and visit timing were evaluated. Women continuing with a third self-injection were followed up at home after their next scheduled injection date. At each interaction, participants were interviewed to learn about their experience; additional questions during the final home visit focused on storage and disposal practices, and acceptability.ResultsAmong the 337 participants followed up 3 months post-training, 310 self-injected, and 87% did so competently. Factoring in women who declined to self-inject, electing to have the provider administer the injection instead, a total of 80% [95% confidence interval (CI)=75-84%] self-injected competently 3 months post-training, and 84% [95% CI=80-88%] reinjected on time, while 72% [95% CI=67-77%] were both on time and competent. The vast majority (93%) expressed a desire to continue.ConclusionsSelf-injection is feasible and acceptable among most study participants in Senegal.ImplicationsThese first research results on contraceptive self-injection in West Africa indicate initial feasibility and acceptability of the practice. Results underscore the importance of designing self-injection programs that empower and support women, including those with limited education.

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Clinical evaluation of large volume subcutaneous injection tissue effects, pain, and acceptability in healthy adults.

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