Comparison of sedation with dexmedetomidine/atipamezole administered subcutaneously at GV20 acupuncture point with usual routes of administration in dogs presented for orthopaedic radiographs.

OBJECTIVES: To evaluate the efficacy of subcutaneous administration of dexmedetomidine/atipamezole at the Governing Vessel 20 (GV20) acupuncture point compared with other administration routes (intramuscular and intravenous) in dogs presented for orthopaedic radiographs. MATERIALS AND METHODS: Prospective, randomised, blinded, controlled clinical study. Sixty-four client-owned dogs were randomly injected with 200 µg/m2 of dexmedetomidine intramuscular (lumbar muscles) (n=20), intravenous (n=23) or subcutaneous at the GV20 point (n=21). Following radiographs, dogs received 2000 µg/m2 of atipamezole intramuscular (n=31), or subcutaneous at the GV20 point (n=27). Degree and time to sedation and recovery were assessed using a sedation scale and a Dynamic and Interactive Visual Analog Scale (DIVAS). Clinical physiological variables and adverse events were used. Statistical linear mixed-effect models (analysis of variance) and Cox models were performed. Significance was set at P-value <0.05. RESULTS: Sedation was insufficient to perform orthopaedic radiographs in six dogs in the intramuscular group. The time to sedation was significantly longer, and sedation scale and DIVAS scores were significantly lower in the intramuscular group. The intravenous group had significantly higher sedation scale and DIVAS scores than the GV20 group. No significant differences were observed between the intramuscular and GV20 recovery groups, although the time effect was significantly more pronounced in the GV20 recovery group. CLINICAL SIGNIFICANCE: Subcutaneous administration of dexmedetomidine and atipamezole at GV20 provided effective sedation and recovery in dogs undergoing orthopaedic radiographic studies. GV20 administration provided a clinically similar level of sedation to the intravenous route, and greater and faster sedation and similar recovery to intramuscular.

A 52 weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world.

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety.

Self-injectable extended release formulation of Remdesivir (SelfExRem): A potential formulation alternative for COVID-19 treatment.

There has been a growing and evolving research to find a treatment or a prevention against coronavirus 2019 (COVID-19). Though mass vaccination will certainly help in reducing number of COVID-19 patients, an effective therapeutic measure must be available too. Intravenous remdesivir (RDV) was the first drug receiving Food and Drug Administration (FDA) approval for the treatment of COVID-19. However, in a pandemic like COVID-19, it is essential that drug formulations are readily available, affordable and convenient to administer to every patient around the globe. In this study, we have developed a Self-injectable extended release subcutaneous injection of Remdesivir (SelfExRem) for the treatment of COVID-19. As opposed to intravenous injection, extended release subcutaneous injection has the benefits of reducing face-to-face contact, minimizing hospitalization, reducing dosing frequency and reducing overall health care cost. SelfExRem was developed using a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), dissolved in a biocompatible vehicle. Six different batches were formulated using 2 different grades of low molecular weight PLGA and 3 different PLGA concentration. The force of injection of various polymeric solutions through 23-30-gauge needles were analyzed using a TA.XTplus texture analyzer. The time required for injection was evaluated both manually and by using an autoinjector. In vitro release of all the batches were carried out in 1% v/v tween 80 in phosphate buffer saline. The study indicated that SelfExRem developed with15% w/v PLGA(75:25) provided a steady release of drug for 48 h and may be a breakthrough approach for the treatment of COVID-19.

Pain-less injection: principles and pearls.

There has been an exponential growth in the number of dermatologic procedures performed over the past two decades. This surge in procedural volumes is accompanied by increasing utilization of local anesthetics. A proper technique in administering local anesthesia is necessary to minimize pain and promote comfort, as it is often regarded as the most painful part of cutaneous procedures. Pain is a psychophysiological phenomenon that involves attention, cognitive appraisal, and emotion. Sensory feedback and anxiety are two important aspects of pain perception. This article aims to introduce a novel way that minimizes pain and discomfort associated with local anesthetics. It is the authors' experience that painless injection is achievable by keeping syringes/needles out of sight, proceeding with injection without pre-procedure warning, and engaging patients in a conversation or simple tasks.

Comparing local anesthetic infiltration of the peritonsillar region and glossotonsillar sulcus for post-tonsillectomy pain management.

PURPOSE: The objective of this study was to compare the efficacy of peritonsillar and glossotonsillar sulcus infiltration with bupivacaine to manage postoperative pain and odynophagia in children undergoing tonsillectomy. METHODS: Fifty children (5-10 years of age) undergoing tonsillectomy due to recurrent tonsillar infections were enrolled in the study and assigned into two groups receiving either pre-incisional peritonsillar (Group 1, n = 25) or glossotonsillar sulcus (Group 2, n = 25) infiltration with 1 mg/kg bupivacaine (0.5%) totaling 5 mL in volume. At different time intervals following arrival to the post-anesthesia care unit (PACU), the participants in each group were evaluated for pain using the modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) and for odynophagia using a four-point scale (1-none, normal or no difficulty with swallowing, 2-mild, mild difficulty with swallowing, 3-moderate, moderate difficulty with swallowing, and 4-severe, no swallowing or swallowing only with maximal effort). Additional parameters were assessed for 24 h post-surgery, including time to first administration of analgesic, additional analgesic requirements, nausea/vomiting, allergic reaction, and bleeding. RESULTS: Infiltration of either region with bupivacaine yielded similar analgesic effects at different times following the surgery (P = 0.065). Time to first analgesic treatment and additional analgesic requirements were not significantly different between groups (P = 0.181). Compared to the Group 1, Group 2 was associated with significantly lower odynophagia scores at different times after the surgery (P = 0.020). CONCLUSION: Present results indicate that the infiltration of local anesthetics to glossotonsillar sulcus is a safe, practical, and effective pain management intervention without risk of significant side effects for children undergoing tonsillectomy.

The Calvarial Injection Assay.

This chapter describes the calvarial injection method, whereby the effect of a substance on bone is tested by subcutaneous injection over the calvarium of a mouse. This assay allows testing of the effect of substances on both bone resorption and bone formation in a relatively simple in vivo model. The analysis is carried out by histological means, usually in glycolmethacrylate-embedded tissue, allowing for histochemical analysis and for a variety of different histological staining methods which are also described in detail.

GM1 Acupoint Injection Improves Mental Retardation in Children with Cerebral Palsy.

To study the clinical effectiveness and mechanism of GM1 acupoint injection therapy on mental retardation for children with cerebral palsy (CP). A total of 90 children with CP were divided into acupoint injection group (group A), subcutaneous injection group (group B), and control group (group C). Another 30 healthy children were set as a healthy control group (group D). The Mental Developmental Index (MDI), Psychomotor Developmental Index (PDI), and hemodynamic parameters in the cerebral arteries were measured before and after treatment. After three treatment courses, the MDI and PDI in groups A, B, and C were increased, and the increase in group A was most obvious (P < 0.05). Peak systolic velocity, mean velocity, and end-diastolic velocity were also elevated in group A, and after three treatment courses, resistance index decreased with a statistical significance (P < 0.05). However, there were no significant changes in groups B and C (P > 0.05). For all groups, neuron-specific enolase levels decreased and total superoxide dismutase increased after treatment. Acupoint injection therapy combined with conventional rehabilitation therapy demonstrated significant effects on cerebral hemodynamic conditions for children with CP.

Knowledge and use of sterile water injections amongst midwives in the United Kingdom: A cross-sectional study.

BACKGROUND: The use of sterile water injections (SWI) for the relief of pain in labour is popular amongst midwives in countries such as Sweden and Australia. Anecdotal reports suggest the procedure is used less commonly in the United Kingdom (UK) and that a number of barriers to introducing the practice may exist. OBJECTIVE: The objective of this study was to explore the awareness and use of SWI amongst midwives in the UK. DESIGN: A cross-sectional study using an internet-based questionnaire. PARTICIPANTS: Midwives with Nursing and Midwifery Council Registration and currently practicing. SETTING: The questionnaire was distributed via the Royal College of Midwives Facebook page and Twitter account. Invitations to participate were also sent to Heads of Midwifery to distribute to staff. FINDINGS: Three hundred and ninety-eight midwives completed the survey. Eighty-two percent of midwives did not use SWI in practice although 69% would consider learning the procedure. There was considerable variation in techniques amongst midwives that did provide SWI. The lack of available practice guidelines and the advice from the National Institute for Health and Care Excellence to not use SWI were cited as the main barriers. KEY CONCLUSIONS: SWI use is uncommon in the UK although midwives are interested in incorporating the procedure into practice. IMPLICATIONS FOR PRACTICE: National guidance on SWI and the lack of information and training is restricting the use of the procedure in practice, despite SWI being widely used in other countries and being effective in the treatment of pain in labour.

Differentiating Nonpermanent Injectable Fillers: Prevention and Treatment of Filler Complications.

Though the incidence of complications and adverse events with dermatological fillers is inherently low, practitioners should be well versed in both prevention of filler complications and the treatment algorithms for addressing "granulomas," nodules, infection, and vascular compromise. Appropriate preventative measures, coupled with timely and effective treatment, are critically important for patient safety and satisfaction. In addition to the preventive measures and treatment algorithms outlined here, the authors emphasize that the broad classification and treatment of nodules as "granulomas" is likely to lead to ineffective treatment, or worse, unnecessary exposure to incorrect treatment. In practice, nodules are classified and treated based on clinical manifestation (eg, late vs early or noninflammatory vs inflammatory) rather than on histology. Indeed, classification of a nodule as a granuloma requires a histological examination, rarely available (or necessary) in clinical practice to guide treatment. Thus, the apparent inflammatory nature of the nodule and the time of onset should drive treatment approach. The treatment algorithms presented here are based on these clinically meaningful parameters.

Reduced pain when injecting lidocaine. / Mindre smerte ved lokalbedøvelse.

Pain on injection of lidocaine is often considered a necessary evil, but it can be reduced by simple means.

Subcutaneous and Sublingual Immunotherapy in a Mouse Model of Allergic Asthma.

Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2 inflammatory response with involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high production of immunoglobulin E (IgE) antibodies. Consequently, renewed allergen exposure results in a classic allergic response with a distinct early and late phase, both resulting in bronchoconstriction and shortness of breath. Allergen specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma and both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have proven clinical efficacy in long term suppression of the allergic response. Although these treatments are very successful for rhinitis, application of AIT in asthma is hampered by variable efficacy, long duration of treatment, and the risk of severe side-effects. A more profound understanding of the mechanisms by which AIT achieves tolerance to allergens in sensitized individuals is needed to improve its efficacy. Mouse models have been very valuable as a preclinical model to characterize the mechanisms of desensitization in AIT and to evaluate novel approaches for improved efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen absorbed to aluminum hydroxide to induce allergic sensitization, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of the allergen as immunotherapy treatment. Finally, mice are challenged by three intranasal allergen administrations. We will describe the protocols as well as the most important read-out parameters including measurement of invasive lung function measurements, serum immunoglobulin levels, isolation of broncho-alveolar lavage fluid (BALF), and preparation of cytospins. Moreover, we describe how to restimulate lung single cell suspensions, perform flow cytometry measurements to identify populations of relevant immune cells, and perform ELISAs and Luminex assays to measure the cytokine concentrations in BALF and lung tissue.

Antioxidative and Neuroprotective Effects of Curcumin in an Alzheimer's Disease Rat Model Co-Treated with Intracerebroventricular Streptozotocin and Subcutaneous D-Galactose.

Epidemiological data imply links between the increasing incidences of Alzheimer's disease (AD) and type 2 diabetes mellitus. In this study, an AD rat model was established by combining treatments with intracerebroventricular streptozotocin (icv-STZ) and subcutaneous D-galactose, and the effects of curcumin on depressing AD-like symptoms were investigated. In the AD model group, rats were treated with icv-STZ in each hippocampus with 3.0 mg/kg of bodyweight once and then were subcutaneously injected with D-galactose daily (125 mg/kg of bodyweight) for 7 weeks. In the curcumin-protective group, after icv-STZ treatment, rats were treated with D-galactose (the same as in the AD model group) and intraperitoneally injected with curcumin daily (10 mg/kg of bodyweight) for 7 weeks. Vehicle-treated rats were treated as control. Compared with the vehicle control, the amount of protein carbonylation and glutathione in liver, as well as malondialdehyde in serum, were upregulated but glutathione peroxidase activity in blood was downregulated in the AD model group. The shuttle index and locomotor activity of rats in the AD model group were decreased compared with the vehicle control group. Furthermore, AD model rats showed neuronal damage and neuron loss with formation of amyloid-like substances and neurofibrillary tangles, and the levels of both ß-cleavage of AßPP and phosphorylation of tau (Ser396) were significantly increased compared with the vehicle control group. Notably, compared with the AD model group, oxidative stress was decreased and the abilities of active avoidance and locomotor activity were improved, as well as attenuated neurodegeneration, in the curcumin-protective group. These results imply the applications of this animal model for AD research and of curcumin in the treatment of AD.

Double-dorsal versus single-volar digital subcutaneous anaesthetic injection for finger injuries in the emergency department: A randomised controlled trial.

OBJECTIVE: The objective of this present study is to compare pain associated with the double-dorsal versus a single-volar subcutaneous injection in the provision of digital anaesthesia for finger injuries presenting to the ED. METHODS: A randomised controlled trial from November 2012 to January 2014 at a single adult tertiary-referral hospital. ED patients with finger injuries requiring digital anaesthesia was randomised to either the double-dorsal or a single-volar subcutaneous injection technique. The primary outcome was patient reported injection pain measured on a 100 mm visual analogue scale with the assessor blinded to the injection technique. The secondary outcome was success of anaesthesia defined as ability to perform the assessment and treatment without further anaesthetic supplementation after 5 min. RESULTS: Eighty-six patients were enrolled. Median (IQR) age was 34 (24-47) years and 79% were men. The majority (66.3%) had distal phalanx injuries. Forty patients were randomised to the double-dorsal and 46 to a single-volar subcutaneous injection technique. The mean (standard deviation) pain score of the double-dorsal injection was 39.1 (24.2) and a single-volar injection was 37.3 (24.5) with a difference of 1.8 (95% CI -8.8 to 12.3). Digital anaesthesia was successful in 64.9% of the double-dorsal and 71.7% of the single-volar subcutaneous injections, a difference of 6.8% (95% CI -12.7 to 26.3). CONCLUSION: In ED patients with finger injuries requiring digital anaesthesia, both the double-dorsal or single-volar subcutaneous injection techniques have similar pain of injection and success rates of anaesthesia. Single-volar injection appears suitable alternative to the commonly performed double-dorsal injection in the ED.

Evaluation of mesotherapy as a transdermal drug delivery tool.

BACKGROUND: There has been no research about the exact mechanism of transdermal drug delivery during mesotherapy. OBJECTIVE: We aimed to evaluate whether the commercial mesogun can be an appropriate technique for a transdermal drug delivery. MATERIALS AND METHODS: We injected blue ink into the polyurethane foam or pig skin with three types of mesotherapy using a commercial mesogun, or local made intradermal injector, or a manual injection of syringe. To assess the internal pressure of the cylinder and drug delivery time, we designed the evaluation setup using a needle tip pressure transducer. RESULT: All types of injectors induced adequate penetration of blue ink into the polyurethane foam without backflow. In the pig skin, blue ink leaked out rapidly with the backward movement of the needle in the commercial mesogun in contrast to the local made injector or the manual injection of syringe. When the time for backward movement of the syringe approaches 1000 ms, the cylinder pressure of the syringe is saturated at around 25 mmHg which can be translated into the dermal pressure of the pig skin. CONCLUSION: There should be sufficient time between the insertion and withdrawal of the needle of injector for the adequate transdermal drug delivery and it must be considered for mesotherapy.

Minimizing the pain of local anesthesia injection.

BACKGROUND: Local anesthetic injection is often cited in literature as the most painful part of minor procedures. It is also very possible for all doctors to get better at giving local anesthesia with less pain for patients. The purpose of this article is to illustrate and simplify how to inject local anesthesia in an almost pain-free manner. METHODS: The information was obtained from reviewing the best evidence, from an extensive review of the literature (from 1950 to August of 2012) and from the experience gained by asking over 500 patients to score injectors by reporting the number of times they felt pain during the injection process. RESULTS: The results are summarized in a logical stepwise pattern mimicking the procedural steps of an anesthetic injection-beginning with solution selection and preparation, followed by equipment choices, patient education, topical site preparation, and finally procedural techniques. CONCLUSIONS: There are now excellent techniques for minimizing anesthetic injection pain, with supporting evidence varying from anecdotal to systematic reviews. Medical students and residents can easily learn techniques that reliably limit the pain of local anesthetic injection to the minimal discomfort of only the first fine needlestick. By combining many of these conclusions and techniques offered in the literature, tumescent local anesthetic can be administered to a substantial area such as a hand and forearm for tendon transfers or a face for rhytidectomy, with the patient feeling just the initial poke.

Mesotherapy for local fat reduction.

Mesotherapy, which is the injection of substances locally into mesodermally derived subcutaneous tissue, developed from empirical observations of a French physician in the 1950s. Although popular in Europe for many medical purposes, it is used for local cosmetic fat reduction in the United States. This paper reviews manuscripts indexed in PubMed/MEDLINE under 'mesotherapy', which pertains to local fat reduction. The history of lipolytic mesotherapy, the physiology of body fat distribution, the mechanism of action of different lipolytic stimulators and their increased efficacy in combination are reviewed. Mesotherapy falls into two categories. Lipolytic mesotherapy using lipolytic stimulators requires more frequent treatments as the fat cells are not destroyed and can refill over time. Ablative mesotherapy destroys fat cells with a detergent, causes inflammation and scarring from the fat necrosis, but requires fewer treatments. The historic and empiric mixing of sodium channel blocking local anaesthetics in mesotherapy solutions inhibits the intended lipolysis. Major mesotherapy safety concerns include injection site infections from poor sterile technique. Cosmetic mesotherapy directs the area from which fat is lost to improve self-image. Studies were of relatively small number, many with limited sample sizes. Future research should be directed towards achieving a Food and Drug Administration indication rather than continuing expansion of off-label use.

[Methodology for preclinical assay of pseudoallergy of injectable drugs (II) rat model for assay of cutaneous pseudoallergy induced by injections].

OBJECTIVE: To develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs. METHOD: Rats cutaneous anaphylactoid reaction model was developed by intravenous injection of 0. 6% Evans blue(EB) followed by intracutaneous injection of test substance solutions 50 microL. Diameters of subcutaneous blue spots and EB exudation were assayed. RESULT: Rat anaphylactoid reaction was characterized as vascular hyperpermeability which was measured by diameters of blue spots inside the skin and the EB exudation of the blue spots. Compound 48/80 caused severe bluing and EB exudation in the skin by inducing obvious vascular hyperpermeability which indicated that it can induce rat skin pseudoallergy. Normal saline or 5% glucose injection showed no obvious reactions. The rat pseudoallergy model was validated by intracutaneous injections of western drug injections and Chinese medicine. CONCLUSION: Rats could be developed into skin pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.

Increasing local blood flow by warming the application site: beneficial effects on postprandial glycemic excursions.

The absorption profile of rapid-acting insulin analogs delivered subcutaneously is slow compared with physiological insulin. Shorter time to peak and shorter duration of insulin action are important steps toward reducing high postprandial blood glucose concentrations in diabetes therapy and are critical for the development of a closed-loop insulin delivery system. Many attempts have been made to develop more rapid-acting insulins. Since the 1950s, different approaches, such as jet injectors and sprinkler needles, which try to increase the absorption areas of injected insulin, have been developed; however, none of them are commonly used in diabetes therapy. Massage and heat increase tissue blood perfusion and, thereby, the absorption of subcutaneously applied insulin. The main focus of this article is a novel device that allows local application of heat to human skin. The device can be connected to a regular insulin pump. This device could demonstrate a significant effect on insulin absorption and postprandial glucose excursions in multiple clinical trials.