In this phase 2 trial, nemolizumab at all monthly doses significantly improved pruritus in patients with moderate-to-severe atopic dermatitis, which showed the efficacy of targeting interleukin-31 receptor A. The limited size and length of the trial preclude conclusions regarding adverse events. (Funded by Chugai Pharmaceutical; XCIMA ClinicalTrials.gov number, NCT01986933 .).

Nemolizumab for up to 64 weeks was efficacious and overall well tolerated in patients with moderate-to-severe atopic dermatitis inadequately controlled by topical therapy.

SummaryBackground The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. Objectives To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. Methods In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. Results No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about À50% at week 4 with CIM331 compared with À20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. Conclusions A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone. CIM331 may become a novel therapeutic option for AD by inhibiting IL-31.

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The present study compared changes in cuff pressure by head and neck position between high-volume low-pressure (HVLP) and taper-shaped (taper) cuffs in a prospective randomized clinical trial. Methods. Forty patients were intubated using tracheal tubes with either HVLP (n = 20; HVLP group) or taper-shaped (n = 20; Taper group) cuffs. Initial cuff pressure was adjusted to 15, 20, or 25 cmH2O in the neutral position. Cuff pressure was evaluated after changing the head and neck positions to flexion, extension, and rotation. Results. Cuff pressure significantly increased with flexion in both HVLP and Taper groups at all initial cuff pressures. It significantly increased with extension in the HVLP group, but not in the Taper group. Cuff pressure did not significantly differ with rotation in either group and was significantly smaller in the Taper group during flexion and extension than in the HVLP group, regardless of initial cuff pressure. Conclusion. Cuff pressure changes with head and neck flexion and extension were smaller in the Taper group than in the HVLP group. Our results highlight the potential for taper cuffs to prevent excessive cuff pressure increases with positional changes in the head and neck. This trial is registered with UMIN000016119.

Atopic dermatitis negatively impacts work productivity. This study investigated the impact of nemolizumab on work productivity and activity impairment in adults with moderate to severe atopic dermatitis inadequately controlled by topical treatments in a two‐part, phase II, randomized control trial. The Work Productivity and Activity Impairment – Atopic Dermatitis questionnaire was an exploratory end‐point. Part A was a 12‐week, placebo‐controlled study in which patients received s.c. nemolizumab 0.1, 0.5 or 2.0 mg/kg every 4 weeks or 2.0 mg/kg every 8 weeks. Part B was a 52‐week extension in which all patients received active treatment. A total of 138 patients had Work Productivity and Activity Impairment – Atopic Dermatitis data; 104 were employed at baseline. At week 12, patients receiving nemolizumab every 4 weeks showed greater mean (standard error) Work Productivity and Activity Impairment – Atopic Dermatitis improvement (score reduction) from baseline versus placebo: Percent Work Time Missed (0.1, 0.5 or 2.0 mg/kg vs placebo): –4.0% (3.9%), –1.7% (4.2%) and –1.6% (4.2%) versus 4.9% (4.5%); Percent Impairment While Working, –15.8% (6.0%), –24.1% (6.5%) and –34.3% (6.4%) versus –16.5% (7.1%); Percent Overall Work Impairment, –16.3% (6.0%), –23.1% (6.5%) and –34.5% (6.3%) versus –16.6% (7.1%); and Percent Activity Impairment, –13.4% (5.3%), –23.5% (5.3%) and –41.9% (5.5%) versus –10.9% (5.7%). Improvements were sustained through week 64. Nemolizumab‐treated patients with moderate to severe atopic dermatitis reported improvements in Work Productivity and Activity Impairment through week 64.

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BackgroundDuring resuscitation, when it is difficult or impossible to establish peripheral venous access, intraosseous route (IO) is considered as an alternative to a central venous line. However, it is sometimes difficult for obtain IO access with conventional manual bone puncture needle. Recently, powered mechanical bone marrow needle was developed. We compared the performance of the manual and mechanical bone marrow puncture needle for adult, child and infant simulation.Methods22 anesthesiologists, who has never used bone marrow puncture needle, performed manual (Dickman™, Cook Medical) or mechanical (EZ-IO™, Teleflex) bone marrow puncture to simulated adult, child and infant tibia. Puncture success rate, insertion time, and subjective difficulty utilizing visual analogue scale was assessed.ResultsIn adult settings, with the manual bone marrow needle, only 3 of 22 participants could succeed in the IO route keep, while all participants did in the mechanical bone marrow puncture needle (P < 0.001). In child and infant settings, all trials were successful in both manual and mechanical bone marrow puncture needles (P = 1.00). In adult simulations, IO insertion took significantly longer with manual bone marrow puncture (54.8 ± 15.8 s) than without compressions (3.7 ± 2.1 s; P < 0.001). In child and infant simulations, the IO insertion time was significantly smaller in mechanical trials than in manual ones (child simulation; manual 9.3 ± 4.6 s, mechanical 2.2 ± 0.8 s, P < 0.001, infant simulation; manual 2.0 ± 1.1 s, mechanical 1.5 ± 0.8 s, P = 0.003).Although the VAS score was not significantly higher with manual trials than in mechanical trials among the three simulations (adult simulation, P < 0.001, child simulation, P < 0.001, infant simulation P = 0.006).ConclusionsWe conclude that in simulations managed by anesthesiologists who had no clinical experiences with bone marrow puncture, the mechanical bone puncture needle performed better than the manual one for emergency IO route access.