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The only causative treatment for IgE-mediated allergies is allergen-specific immunotherapy. However, fewer than 5% of allergy patients receive immunotherapy because of its long duration and risk of allergic side effects. We aimed at enhancing s.c. immunotherapy by direct administration of allergen into s.c. lymph nodes. The objective was to evaluate safety and efficacy compared with conventional s.c. immunotherapy. In a monocentric open-label trial, 165 patients with grass pollen-induced rhinoconjunctivitis were randomized to receive either 54 s.c. injections with pollen extract over 3 years [cumulative allergen dose 4,031,540 standardized quality units (SQ-U)] or 3 intralymphatic injections over 2 months (cumulative allergen dose 3,000 SQ-U). Patients were evaluated after 4 months, 1 year, and 3 years by nasal provocation, skin prick testing, IgE measurements, and symptom scores. Three low-dose intralymphatic allergen administrations increased tolerance to nasal provocation with pollen already within 4 months (P < 0.001). Tolerance was long lasting and equivalent to that achievable after standard s.c. immunotherapy (P = 0.291 after 3 years). Intralymphatic immunotherapy ameliorated hay fever symptoms (P < 0.001), reduced skin prick test reactivity (P < 0.001), decreased specific serum IgE (P < 0.001), caused fewer adverse events than s.c. immunotherapy (P = 0.001), enhanced compliance (P < 0.001), and was less painful than venous puncture (P = 0.018). In conclusion, intralymphatic allergen administration enhanced safety and efficacy of immunotherapy and reduced treatment time from 3 years to 8 weeks.

Background Polynucleotide (PN) filler often causes pain and can lead to delivery inaccuracies when applied via intradermal injection using a traditional needle. Aims To evaluate the efficacy of treatment and the pain during the procedure using conventional needle injection versus a needle‐free jet system for intradermal PN filler application. Methods In this split‐face clinical trial, 10 Korean subjects were enrolled. Each subject received an intradermal injection of PN filler on one side of the face and a needle‐free jet injection using CureJet on the other side. Assessments included global and 3D skin imaging at each visit. Pain intensity was evaluated using visual analogue scale (VAS) scores during the injection. Additionally, patient satisfaction and adverse events were documented. Results Findings revealed that Global Aesthetic Improvement Scale scores and patient satisfaction were significantly higher with the CureJet compared to the needle injection method. VAS scores were notably lower on the CureJet side. Improvements in both pore and wrinkle indices were observed from baseline, with a more pronounced improvement rate on the CureJet side compared to the needle injection side. Conclusions Needle‐free injection of PN for aging skin was found to be effective in enhancing pore and wrinkle improvement, while reducing associated discomfort.

Intradermal bacille Calmette-Guérin (BCG) vaccination by needle-free, disposable-syringe jet injectors (DSJI) is an alternative to the Mantoux method using needle and syringe (NS). We compared the safety and immunogenicity of BCG administration via the DSJI and NS techniques in adults and newborn infants at the South African Tuberculosis Vaccine Initiative (SATVI) research site in South Africa. Thirty adults and 66 newborn infants were randomized 1:1 to receive intradermal BCG vaccine (0.1mL in adults; 0.05mL in infants) via DSJI or NS. Wheal diameter (mm) and skin fluid deposition at the site of injection (SOI) were measured immediately post-vaccination. Adverse events and SOI reactogenicity data were collected 30min and 1, 2, 4, and 12 weeks after vaccination for adults and at 30min and 4, 10, and 14 weeks for infants. Blood was collected in infants at 10 and 14 weeks to assess BCG-specific T-cell immune responses. More infant BCG vaccinations by DSJI deposited >5μL fluid on the skin surface, compared to NS (49% versus 9%, p=0.001). However, all 12 infant vaccinations that did not produce any SOI wheal occurred in the NS group (36%, p<0.001). Median wheal diameter, in participants for which an SOI wheal formed, did not differ significantly between groups in infants (combined 3.0mm IQR 2.0 to 4.0, p=0.59) or in adults (combined 9.0mm IQR 7.0 to 10.0, p=0.13). Adverse events were similar between study arms. Proportion of participants with BCG scars after three months did not differ in adults (combined 97%, p=0.67) or infants (combined 62%, p=0.13). Frequencies of BCG-specific clusters of differentiation 4 (CD4) and clusters of differentiation 8 (CD8) T-cells co-expressing IFN-γ, TNF-α, IL-2, and/or IL-17 were not different in the DSJI and NS groups. BCG vaccination of newborn infants via DSJI was more likely to deliver an appropriate intradermal wheal at the SOI as compared to NS, despite leaving more fluid on the surface of the skin. Safety, reactogenicity, and antigen-specific T-cell immune responses did not differ between DSJI and NS techniques.

To draw up evidence-based guidelines to make injections safer. A development group summarized evidence-based best practices for preventing injection-associated infections in resource-limited settings. The development process included a breakdown of the WHO reference definition of a safe injection into a list of potentially critical steps, a review of the literature for each of these steps, the formulation of best practices, and the submission of the draft document to peer review. Eliminating unnecessary injections is the highest priority in preventing injection-associated infections. However, when intradermal, subcutaneous, or intramuscular injections are medically indicated, best infection control practices include the use of sterile injection equipment, the prevention of contamination of injection equipment and medication, the prevention of needle-stick injuries to the provider, and the prevention of access to used needles. The availability of best infection control practices for intradermal, subcutaneous, and intramuscular injections will provide a reference for global efforts to achieve the goal of safe and appropriate use of injections. WHO will revise the best practices five years after initial development, i.e. in 2005.

Background. Individuals infected with human immunodeficiency virus (HIV) are at increased risk for severe influenza, yet immune responses to standard-dose intramuscular (IM) influenza vaccine are suboptimal in this population. Intradermal (ID) delivery of influenza vaccine might improve immune response through enhanced stimulation of dendritic cells. Methods. We conducted a randomized, double-blind, controlled trial to compare the immunogenicity of off-lable standard-dose (15 μg) ID vs standard-dose (15 μg) IM inactive influenza vaccine in HIV-infected men in Bangkok, Thailand. The primary study outcome was seroconversion (minimum titer of 1:40 and ≥4-fold rise in antibody titer) at 1 month postvaccination based on serum hemagglutination inhibition antibody titers against each vaccine strain. Adverse events (AEs) in the 7 days following vaccination were also assessed. Results. We enrolled 400 HIV-infected participants; 200 were randomly assigned to receive IM and 200 ID vaccine. Vaccine arms were well-balanced with respect to age, CD4 cell count, HIV RNA load, and antiretroviral treatment. Percentage of seroconversion to all (ID 14% vs IM 15%; P = .8) or at least 1 (ID 69% vs IM 68%; P = .7) of the 3 vaccine strains did not differ significantly between ID vs IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection-site AEs compared with participants who received IM vaccine (77% vs 27%). Conclusions. There were no significant differences in the immunogenicity of standard-dose ID vs IM influenza vaccine in this HIVinfected population in Thailand. Additional strategies to enhance immune responses to influenza vaccine among HIV-infected persons are needed. Clinical Trials Registration. NCT01538940.

Vaccinating healthcare workers against influenza takes tens of thousands of hours of work annually. This study was undertaken to determine the acceptability, success rate, and time to vaccinate healthcare workers in nurse-led groups that self-vaccinated with intradermal influenza vaccine compared with nurse-administered intramuscular vaccine. Volunteer hospital workers were randomly assigned to groups that either self-administered intradermal influenza vaccine (Intanza®) in a nurse-led group or received nurse-administered intramuscular vaccine (Vaxigrip®). Research assistants timed vaccination procedures; pre- and post-injection questionnaires assessed acceptability and reactogenicity. 810 adults, 21–69 years of age, from two study sites were vaccinated: 401 self-administered the intradermal vaccine while 409 received their intramuscular vaccine from a nurse. Of those who self-administered for the first time, 98.5% were successful on their first attempt with an additional 1.5% on their second attempt. Acceptability was high: 96% were very or somewhat certain that they administered the vaccine correctly, 83% would choose intradermal influenza vaccine again and of those, 75% would choose self-administration again, if given the choice. It took 51.3–72.6s per person for the nurses to guide the groups through the self-administration process, which was significantly less time than it took to individually administer the intramuscular vaccines (93.6s). Self-administration of intradermal influenza vaccine by people working in healthcare settings is a possible alternative to nurse administered vaccinations, with nurse-led group sessions a good way of teaching the technique while being available to respond to unanticipated problems (NCT01665807).

ObjectivesTo compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response.MethodsMONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24.ResultsSarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (−3.28 vs −2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences.ConclusionsSarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects.Trial registration numberNCT02332590.

Abstract Purpose The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). Methods In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Results Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. Conclusions OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.

In this randomized, controlled trial involving women in South Africa and Uganda, twice-yearly subcutaneous lenacapavir was superior to daily oral emtricitabine–tenofovir disoproxil fumarate in preventing HIV infection.

The present study was undertaken with controls using equal doses ID and IM plus the standard full dose IM to assess the role of route of vaccine in immunogenicity of inactivated influenza vaccine. The study was a prospective, randomized, active-controlled, open label clinical trial conducted in healthy young adult outpatients to compare the effect of route (IM versus ID) on antibody responses to influenza vaccine. Volunteers received 3, 6 or 9 μg of vaccine by ID or IM route; 15 μg IM was also studied. Low doses of vaccine given by either route were almost as immunogenic as the standard 15 μg IM dose of influenza vaccine. ID route was not superior to IM vaccine at inducing antibodies. ID vaccine induced significantly more local inflammatory response than IM vaccine.