Effectiveness and Safety of Long-Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real-Life Observational Study.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. METHODS: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. RESULTS: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. CONCLUSIONS: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Traditional Chinese medicine auricular point acupressure for the relief of pain, fatigue, and gastrointestinal adverse reactions after the injection of novel coronavirus-19 vaccines: a structured summary of a study protocol for a multicentre, three-arm, single-blind, prospective randomized controlled trial.

OBJECTIVES: To investigate if traditional Chinese medicine (TCM) auricular point acupressure (APA) can alleviate and (or) reduce the pain (including injection site pain, headache, other muscle and joint pain), fatigue, and gastrointestinal adverse reactions (including nausea, vomiting, diarrhea), after the injection of novel coronavirus-19 vaccines (NCVs). TRIAL DESIGN: The study is designed as a multicentre, parallel-group, three-arm, single-blind, prospective, randomized (1:1:1 ratio) study. PARTICIPANTS: More than 360 participants will be recruited from healthy people who vaccinate NCVs in 5 community healthcare centres in the Sichuan province of China and 1 university hospital (Hospital of Chengdu University of Traditional Chinese Medicine). INCLUSION CRITERIA: ①Vaccinators meets the conditions of NCVs injection and have no contraindications to it. The details shall be subject to the instructions of the NCVs used and the statement of medical institutions. The first dose of NCVs injection shall be completed within 24 hours from the time of injection to the time of enrolment; ②No redness, swelling, injury or infection of the skin or soft tissue of both ears, which is not suitable for APA; ③No history of alcohol and adhesive tape contact allergy; ④18-59 years old, regardless of gender; ⑤Those who were able to complete the questionnaire independently at the time of the first and second dose of NCVs and on the 3rd, 7th and 15th day after the first and second dose of NCVs respectively; ⑥Those who agree to participate in the trial and sign the informed consent, and can seriously abide by the precautions after the injection of NCVs and the requirements of traditional Chinese medicine auricular point plasters sticking and acupressure. EXCLUSION CRITERIA: ①Those who are not suitable to be vaccinated because they belong to the contraindication or cautious population; ②Those who have participated in other clinical trials within 4 weeks before the start of this study; ③No chronic/habitual/persistent headache, Muscle or joint pain, fatigue, diarrhea, nausea, retching or vomiting before the injection of NCVs, and no related diseases present (details of this item is listed in full protocol); ④Those who are in use or have received TCMAPA within 2 weeks before the trial; ⑤Pregnant or lactating women; ⑥Participants with other serious primary diseases and psychosis. INTERVENTION AND COMPARATOR: ①Auricular point acupressure group: participants receive bilateral, symptom-specific TCMAPA in 5 auricular points (per side, 10 points bilateral) for 5 days, 3-4 times (about 1 min each time) of self-acupressure per day, after each NCVs injection (10 days in total). ②Sham auricular point acupressure group: participants receive bilateral, none symptom-specific, sham APA in 5 auricular points (per side, 10 points bilateral) for 5 days, 3-4 times (about 1 min each time) of self-acupressure per day, after each NCVs injection (10 days in total). ③Blank control group: Non-intervention blank control. The Hebei medical device Co. Ltd, Hebei, China manufactured the auricular point sticking plasters. MAIN OUTCOMES: Primary outcomes are all scores of visual analogue scale (VAS) based on subjective judgment of the participants included, including VAS score of pain at injection site, headache, muscle and joint pain, fatigue, nausea, retching, vomiting and diarrhea. Time points for outcomes above are the same: ①Immediately after first and second injection of the vaccine (Baseline assessment); ②Three days after first and second injection of the vaccine; ③Seven days after first and second injection of the vaccine; ④Fifteen days after first and second injection of the vaccine. RANDOMISATION: Participants will be randomized in 1:1:1 ratio to each group by computerized random number generator, and independently in each sub-centre. BLINDING (MASKING): Participants, information collectors and statistical evaluators will be blinded between APA group and sham APA group. No blinding in the control group. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): No less than 360 participants will be randomized in 1:1:1 ratio to each group. TRIAL STATUS: Protocol version 2.0 of February 3rd, 2021. Recruitment is expected to start on February 18th, 2021, and to finish on March 12th, 2021. TRIAL REGISTRATION: This trial was registered in the China Clinical Trial Registry (ChiCTR) ( ChiCTR2100043210 ) on 8th February, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Residual strain effects in needle-induced cavitation.

Needle-induced cavitation (NIC) locally probes the elastic and fracture properties of soft materials, such as gels and biological tissues. Current NIC protocols tend to overestimate properties when compared to traditional techniques. New NIC methods are needed in order to address this issue. NIC measurements consist of two distinct processes, namely (1) the needle insertion process and (2) the cavitation process. The cavitation process is hypothesized to be highly dependent on the initial needle insertion process due to the influence of residual strain below the needle. Retracting the needle before pressurization to a state in which a cylindrical, tube-like fracture is left below the needle tip is experimentally demonstrated to reduce the impact of residual strain on NIC. Verification of the critical cavitation pressure equation in this new geometry is necessary before implementing this retraction NIC protocol. Complementary modeling shows that the change in initial geometry has little effect on the critical cavitation pressure. Together, these measurements demonstrate that needle retraction is a viable experimental protocol for reducing the influence of residual strain, thus enabling the confident measurement of local elastic and fracture properties in soft gels and tissues.

Mesotherapy: Safety profile and management of complications.

BACKGROUND: Mesotherapy is a procedure that involves the injection of active substances into the dermis and subcutaneous tissue in order to treat several local medical and cosmetic conditions. Despite being considered as a relatively safe method, a series of adverse reactions can occur due to its wide application and lack of standardization processes. OBJECTIVES: The aim of this paper is to summarize all the mesotherapy-related complications published so far, and to provide an insight into their management. PATIENT/METHODS: Articles derived from the databases, PubMed, EMBASE, and SCOPUS, and published between 1992 and 2018, were analyzed for this review. The study was conducted according to the PRISMA guidelines. RESULTS: In this literature, there is a number of case series and isolated case reports describing various side effects of different severities. The therapeutic management of these complications is-in most cases-individualized. CONCLUSIONS: Larger systematic studies are needed in order to adequately evaluate the safety profile of mesotherapy, and in order to determine standardized therapy parameters, so as to minimize the risk of potential adverse reactions.

Acute Histopathologic Findings Related to Needle Puncture Trauma during Subcutaneous Injection in the Sprague-Dawley Rat Model.

It is important to detect injection site reactions during the nonclinical phases of drug development. However, differentiating between normal changes following needle trauma and changes due to the toxicity of injected drugs can be challenging. Therefore, we used the Sprague-Dawley rat model to evaluate the pathological findings expected following a single subcutaneous injection of normal saline. Rats were subcutaneously administered with normal saline, and the injection sites were examined microscopically. Inflammation was evident in most of the injection sites, mostly in minimal severity. Parakeratosis/epithelial crust was also seen in several sites, and necrosis was observed in a minority of the cases. These findings indicate that needle puncture trauma can present with some degree of inflammation and necrosis. Although limited to a specific time point and strain, this study shows that inflammation following subcutaneous injection can be attributed in part to the needle trauma and not necessarily to the drug itself.

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.

Ninety-day Local Tolerability and Toxicity Study of ND0612, a Novel Formulation of Levodopa/Carbidopa, Administered by Subcutaneous Continuous Infusion in Minipigs.

A 90-day study in Göttingen minipigs was conducted to test the local tolerability and systemic toxicity of ND0612, a novel aqueous solution of carbidopa (CD)/levodopa (LD) intended for the treatment of Parkinson's disease by continuous subcutaneous administration using a discrete infusion pump. To evaluate tissue site reactions, we used a unique study design involving multiple infusion sites to evaluate the effect of dose per site (270/63, 360/45, and 360/84 mg LD/CD), volume of infusion per site (4.5 and 6 ml per site), formulation concentration (60/14 and 60/7.5 mg/ml LD/CD), daily rate of infusion per site (240 µl/hr for16 hr and 80 µl/hr for 8 hr, 320 µl/hr for 16 hr and 100 µl/hr for 8 hr, or 750 µl/hr for 8 hr), frequency (once every 5, 10, 15, or 20 days), and number of infusions (4, 6, or 9) to the same infusion site. No systemic adverse effects were observed. Histopathological changes at infusion sites started with localized minimal necrosis and acute inflammation that progressed to subacute and chronic inflammatory and reparative changes with evidence of progressive recovery following the final infusion. None of the infusion site effects were judged to be adverse, and clinical exposures to ND0612 are not expected to result in adverse responses.

Hair loss at injection sites of mesotherapy for alopecia.

BACKGROUND: The side effects of mesotherapy for treatment of various forms of alopecia are often underreported, while scientific data for its efficacy are severely lacking. OBJECTIVE: To demonstrate the late onset side effects of mesotherapy for alopecia. METHODS: Three patients with androgenetic alopecia showed hair loss after previously uneventful mesotherapy sessions up to 1 year. RESULTS: Clinical, dermoscopic, and histopathological findings suggested an inflammatory scaring process at sites of mesotherapy injections. CONCLUSION: Mesotherapy for androgenetic alopecia may paradoxically induce hair loss and scarring. Proper regulation and monitoring of the use of mesotherapy products for treating hair loss in women, needs to be addressed.

Non-clinical safety assessment of single and repeated administration of gE/AS01 zoster vaccine in rabbits.

HZ/su is an investigational recombinant subunit vaccine for the prevention of shingles, a disease resulting from the reactivation of varicella zoster virus. The vaccine is composed of recombinant varicella zoster virus glycoprotein E (gE), and liposome-based Adjuvant System AS01. To evaluate the potential local and systemic effects of this vaccine, three studies were performed in rabbits. In the first two studies, rabbits received a single intramuscular (IM; study 1) or subcutaneous (SC; study 2) dose of gE/AS01, AS01 alone (in study 2 only) or saline, and the local tolerance was evaluated up to 3 days after administration. Under these conditions, only local inflammatory reactions at the injection sites were detected by microscopic evaluation. In the third study, gE/AS01, AS01 alone or saline, were injected SC or IM on four occasions at 2 week intervals. General health status, local tolerance, ophthalmology, haematology and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed after termination of the study. The only treatment-related changes included a transient increase in neutrophils, C-reactive protein and fibrinogen levels and microscopic signs of inflammation at the injection sites, which are expected observations related to the elicited inflammatory reaction. The SC and IM routes of administration produced similar systemic effects. However, microscopic findings at the injection sites differed. One month after the last injection, recovery was complete in all groups. In conclusion, the single and repeated SC and IM administration of the gE/AS01 vaccine were locally and systemically well-tolerated in rabbits and support the clinical development of the vaccine. Copyright © 2016 John Wiley & Sons, Ltd.