Concept: Subcutaneous injection
To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes.
We assessed whether fully closed-loop insulin delivery (the so-called artificial pancreas) is safe and effective compared with standard subcutaneous insulin therapy in patients with type 2 diabetes in the general ward.
Object Previous studies of systemic and intralesional administration of nonpegylated interferon have shown efficacy against craniopharyngioma. Pegylaion of interferon-α-2b (PI) prolongs the half-life, allowing sustained exposure of the drug over time, and enhances efficacy. The authors report the results of the use of PI in 5 children with recurrent craniopharyngiomas. Methods Five children, ranging in age from 9 to 15 years, with recurrent craniopharyngiomas were treated for up to 2 years with subcutaneous injections of PI at a dose of 1-3 μg/kg/week. Tumor response was assessed using MRI. Results All patients had stable disease or better in response to PI. One patient experienced a recurrence after gross-total resection (GTR). She initially showed an increase in the predominantly cystic tumor after 3 months of treatment, followed by a complete response. She required no further intervention and remains without evidence of disease 10 years after starting treatment. Another patient experienced recurrence 3.3 years after subtotal resection (STR) and radiation therapy. He had complete disappearance of the predominantly cystic component after 4 months of treatment, and a small residual calcified mass remains 5 years later. The third patient experienced recurrence after 3 GTRs. He had a complete response after 7 months of treatment and remains without evidence of disease 19 months after starting treatment. The fourth patient experienced recurrence after 2 STRs. He had a 30% decrease in tumor size after 4 months of treatment, which was maintained for 12 months at which point the cyst began to increase in size. The final patient experienced recurrence after GTR and has stable disease 6 months after starting treatment with PI. Conclusions The use of PI in children with recurrent craniopharyngiomas can result in significant and durable responses and potentially delay or avoid the need for radiation therapy.
The purpose of this study was to directly compare the pharmacokinetic (PK) profile of 22-mg sumatriptan powder delivered intranasally with a novel Breath Powered™ device (11 mg in each nostril) vs a 20-mg sumatriptan liquid nasal spray, a 100-mg oral tablet, and a 6-mg subcutaneous injection.
Abstract Background: Many diabetes patients who require insulin perform multiple subcutaneous injections every day that often cause pain, discomfort, and anxiety. We compared efficacy (glycemic control) and patient preference for two types of needle: a shorter straight needle (32 gauge×4 mm, straight wall; Nippon Becton Dickinson Co., Ltd., Tokyo, Japan; hereafter referred to as BD32S4) and a thinner microtapered needle (33-gauge tip and 28-gauge base×5 mm, double-tapered wall; Terumo Corp., Tokyo, Japan; hereafter referred to as TR33T5) in a single-center study. Patients and Methods: Eighty-four patients with diabetes were enrolled in a randomized, open-label crossover trial. The patients injected their usual insulin dosage with one type of needle for 4 weeks and then switched to the other type for the next 4 weeks. The serum glycated albumin level was measured before and after each 4-week period. Each patient assessed pain during injection on a 150-mm visual analog scale (VAS). Needle preference, perceptions of handling, and acceptance were assessed by the patients, who completed a questionnaire after using each type of needle for 4 weeks. Results: In total, 79 patients completed the study. There was no difference of glycemic control between the two needles. The mean VAS score was -14.5 mm (95% confidence interval, -20.9, -8.0 mm), indicating that the patients perceived less pain with the BD32S4 needle. In the overall evaluation, a significantly higher percentage of patients selected the BD32S4 as the better needle compared with the TR33T5 (60.3% vs. 19.2%; P<0.0001). Conclusions: The BD32S4 needle was more highly evaluated and was preferred by the patients with respect to pain during injection, usability, and visual impression, without having a negative impact on glycemic control. The overall preference of patients for the shorter needle in this study suggests that needle length may be one of the major contributing factors for patients' comfort in insulin injection, although the other relevant factors of needles still need to be considered.
Amyloid is characterized by its fibrillary ultrastructure, and more than 20 proteins have been described to date as possible precursors. Among them, insulin is and enfuvirtide represent the only medications described as amyloidogenic substances. We describe two diabetic patients, who were undergoing long-standing subcutaneous insulin treatment, who developed subcutaneous nodules at the sites of insulin injections. Histopathologic examination demonstrated the presence of eosinophilic and amorphous masses in deep dermis, which stained positive with Congo red, amyloid P substance and anti-human insulin antibody. Whether the type of injected insulin played or not a role in the pathogenesis of the process is still uncertain, since all described patients used both fast-acting and slow acting insulins at the same injection sites. Our second case demonstrated nodular insulin-derived amyloid tumors only at the sites where exclusively fast-acting insulin was injected, which supports the notion that fast-acting insulin may also be the cause of this disorder. Insulin derived nodular amyloidosis is probably underdiagnosed due to the small body of literature in comparison with the prevalence of insulin dependent diabetic patients. This underdiagnosis probably is due to its clinical similarity with the lesions of lipohypertrophy at the sites of insulin injections, which is rarely biopsied.
Nanocarrier administration has primarily been restricted to intermittent bolus injections with limited available options for sustained delivery in vivo. Here, we demonstrate that cylinder-to-sphere transitions of self-assembled filomicelle (FM) scaffolds can be employed for sustained delivery of monodisperse micellar nanocarriers with improved bioresorptive capacity and modularity for customization. Modular assembly of FMs from diverse block copolymer (BCP) chemistries allows in situ gelation into hydrogel scaffolds following subcutaneous injection into mice. Upon photo-oxidation or physiological oxidation, molecular payloads within FMs transfer to micellar vehicles during the morphological transition, as verified in vitro by electron microscopy and in vivo by flow cytometry. FMs composed of multiple distinct BCP fluorescent conjugates permit multimodal analysis of the scaffold’s non-inflammatory bioresorption and micellar delivery to immune cell populations for one month. These scaffolds exhibit highly efficient bioresorption wherein all components participate in retention and transport of therapeutics, presenting previously unexplored mechanisms for controlled nanocarrier delivery.
A needle-free delivery system may lead to improved satisfaction and compliance, as well as reduced anxiety among patients requiring frequent or ongoing injections. This report describes a first-in-man assessment comparing Portal Instruments' innovative needle-free injection system with subcutaneous injections using a 27G needle. Forty healthy volunteer participants each received a total of four injections of 1.0 mL sterile saline solution, two with a standard subcutaneous injection using a 27G needle, and two using the Portal injection system. Perception of pain was measured using a 100-mm visual analog scale (VAS). Injection site reactions were assessed at 2 min and at 20-30 min after each injection. Follow-up contact was made 24-48 h after the injections. Subject preference regarding injection type was also assessed. VAS pain scores at Portal injection sites met the criteria to be considered non-inferior to the pain reported at 27G needle injection sites (i.e., upper 95% confidence bound less than +5 mm). Based on a mixed effects model, at time 0, accounting for potential confounding variables, the adjusted difference in VAS scores indicated that Portal injections were 6.5 mm lower than the 27G needle injections (95% CI -10.5, -2.5). No clinically important adverse events were noted. Portal injections were preferred by 24 (60%) of the subjects (P = 0.0015). As an early step in the development of this new needle-free delivery system, the current study has shown that a 1.0-mL saline injection can be given with less pain reported than a standard subcutaneous injection using a 27G needle.
Hyperkalemia is a common electrolyte disorder that can result in fatal cardiac arrhythmias. Despite the importance of insulin as a lifesaving intervention in the treatment of hyperkalemia in an emergency setting, there is no consensus on the dose or the method (bolus or infusion) of its administration. Our aim was to review data in the literature to determine the optimal dose and route of administration of insulin in the management of emergency hyperkalemia.
Whereas amphibians regenerate lost appendages spontaneously, mammals generally form scars over the injury site through the process of wound repair. The MRL mouse strain is an exception among mammals because it shows a spontaneous regenerative healing trait and so can be used to investigate proregenerative interventions in mammals. We report that hypoxia-inducible factor 1α (HIF-1α) is a central molecule in the process of regeneration in adult MRL mice. The degradation of HIF-1α protein, which occurs under normoxic conditions, is mediated by prolyl hydroxylases (PHDs). We used the drug 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), a PHD inhibitor, to stabilize constitutive expression of HIF-1α protein. A locally injectable hydrogel containing 1,4-DPCA was designed to achieve controlled delivery of the drug over 4 to 10 days. Subcutaneous injection of the 1,4-DPCA/hydrogel into Swiss Webster mice that do not show a regenerative phenotype increased stable expression of HIF-1α protein over 5 days, providing a functional measure of drug release in vivo. Multiple peripheral subcutaneous injections of the 1,4-DPCA/hydrogel over a 10-day period led to regenerative wound healing in Swiss Webster mice after ear hole punch injury. Increased expression of the HIF-1α protein may provide a starting point for future studies on regeneration in mammals.