Nemolizumab in moderate to severe atopic dermatitis: An exploratory analysis of work productivity and activity impairment in a randomized phase II study.

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.

Prolonged severe hemorrhagic shock at a mean arterial pressure of 40 mmHg does not lead to brain damage in rats.

AIM: To examine whether prolonged hemorrhagic shock (HS) at a mean arterial pressure (MAP) of 40 mmHg leads to brain damage. METHODS: Rats were anesthetized with sevoflurane. The HS model consisted of the following phases: I, pressure-controlled HS at a MAP of 40 mmHg; II, fluid resuscitation to normalize blood pressure; III, observations with outcome evaluations in terms of survival, overall performance categories, and neurological deficit scores, as well as evaluation of apoptosis in the hippocampus at 96 h. Each group of six rats was randomized into 60 min (group 1) or 75 min (group 2) each of phases I and II. Three sham rats were anesthetized for 150 min, and then awakened during phase III. RESULTS: The three sham rats as well as five and two of the six rats in groups 1 and 2 (P < 0.05), respectively, survived for up to 96 h. All survivors were functionally normal with overall performance category = 1 and neurological deficit score = 0 at 96 h. Apoptotic neurons were not found in the hippocampus. CONCLUSIONS: The higher mortality in group 2 suggested a more profound effect of HS compared with group 1. However, prolonged HS for 60 or 75 min did not cause functional damage or apoptosis in the hippocampus. These findings suggest that prolonged HS at a MAP of 40 mmHg, as a level at which cerebral blood flow seems preserved by autoregulatory mechanisms, does not lead to brain damage.

Nemolizumab in patients with moderate-to-severe atopic dermatitis: Randomized, phase II, long-term extension study.

BACKGROUND: Nemolizumab, an anti-IL-31 receptor A mAb, improved pruritus, dermatitis, and sleep in adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments in a phase II, 12-week, randomized, double-blind, placebo-controlled study (part A; NCT01986933). OBJECTIVE: We sought to assess the long-term efficacy and safety of nemolizumab injected subcutaneously every 4 weeks (Q4W) or every 8 weeks (Q8W) in a 52-week, double-blind extension (part B). METHODS: During part B, patients continued the previous nemolizumab dose (0.1, 0.5, or 2.0 mg/kg Q4W or 2.0 mg/kg Q8W). Part B end points included percentage improvement from baseline in pruritus visual analog scale and dermatitis scores (including the Eczema Area and Severity Index). RESULTS: Overall, 216 of 264 patients completed part A, and 191 entered part B; 131 completed part B. In 153 patients randomized to nemolizumab in part A, improvement from baseline in pruritus visual analog scale score was maintained/increased from weeks 12 to 64, with greatest improvement in the 0.5-mg/kg Q4W group (percentage change from baseline at week 64: -73.0, -89.6, -74.7, and -79.1 in the 0.1-, 0.5-, and 2.0-mg/kg Q4W and 2.0-mg/kg Q8W groups, respectively). Improvement from baseline in dermatitis scores was also maintained/increased to week 64 (percentage change in Eczema Area and Severity Index score: -68.5, -75.8, -78.9, and -69.3 in the 0.1-, 0.5-, and 2.0-mg/kg Q4W and 2.0-mg/kg Q8W groups, respectively). Over 64 weeks, 83% to 89% had 1 or more adverse events, with no new safety concerns identified. CONCLUSION: 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.

Effect of Cricoid Pressure on the Insertion Efficacy of Six Supraglottic Devices: A Crossover Randomized Simulation Trial.

BACKGROUND: No study has ever compared the efficacy of various types of supraglottic devices (SGDs) for securing the airway under cricoid pressure. OBJECTIVE: This study aimed to evaluate the efficacy of six SGDs, LMA-ProSeal (ProSeal), LMA-Classic (Classic), Laryngeal Tube (LT), LMA-Supreme (Supreme), air-Q (air-Q), and i-gel (i-gel), in airway management under cricoid pressure using a manikin. METHODS: Fifteen novice doctors and 16 experienced doctors used the six SGDs under cricoid or sham pressure on an adult manikin. Insertion time, successful ventilation rate, and subjective insertion difficulty on a visual analogue scale (VAS) were measured. RESULTS: Both novice and experienced doctors had a significantly lower ventilation success rate under cricoid pressure than under sham pressure when using the ProSeal, Classic, and LT, but not when using the other three SGDs. Novice doctors required a significantly longer insertion time under cricoid pressure than under sham pressure with all SGDs. Experienced doctors required a significantly longer insertion time under cricoid pressure than with sham pressure when using the ProSeal, Classic, and LT, but not when using the other three SGDs. Subjective insertion difficulty on VAS was significantly higher under cricoid pressure than under sham pressure with all six SGDs. CONCLUSION: Ventilation success rate under cricoid pressure was significantly lower than under sham pressure when using the ProSeal, Classic, and LT, but not when using the other three SGDs in both novice and experienced doctors.

Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis.

BACKGROUND: Interleukin-31 may play a role in the pathobiologic mechanism of atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks. The primary end point was the percentage improvement from baseline in the score on the pruritus visual-analogue scale (on which a negative change indicates improvement) at week 12. Secondary end points included changes in the score on the Eczema Area and Severity Index (EASI, on which a negative change indicates improvement), and body-surface area of atopic dermatitis. RESULTS: Of 264 patients who underwent randomization, 216 (82%) completed the study. At week 12, among the patients who received nemolizumab every 4 weeks, changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, -59.8% in the 0.5-mg group, and -63.1% in the 2.0-mg group, versus -20.9% in the placebo group (P<0.01 for all comparisons). Changes on the EASI were -23.0%, -42.3%, and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in the placebo group. Respective changes in body-surface area affected by atopic dermatitis were -7.5%, -20.0%, and -19.4% with nemolizumab, versus -15.7% with placebo. Among the patients receiving nemolizumab every 4 weeks, treatment discontinuations occurred in 9 of 53 patients (17%) in the 0.1-mg group, in 9 of 54 (17%) in the 0.5-mg group, and in 7 of 52 (13%) in the 2.0-mg group, versus in 9 of 53 (17%) in the placebo group. CONCLUSIONS: 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 .).

Manual laryngeal fixation facilitates tracheal intubation during chest compression: A randomized crossover manikin study.

PURPOSE: We compared the effectiveness of external manual laryngeal fixation (MLF) for tracheal intubation during chest compression using three laryngoscopes, the Macintosh laryngoscope (McL), McGRATH® MAC (McGRGTH), and Pentax-AWS Airwayscope® (AWS) on an adult manikin. METHODS: Sixteen novice doctors and 15 experienced anesthesiologists performed tracheal intubation during chest compression on an adult manikin using the McL, McGRATH, and AWS with or without MLF. Tracheal intubation time and intubation success rate were measured. RESULTS: In the AWS trial, all novice and experienced doctors successfully secured the airway with or without MLF during chest compression. In McL and McGRATH trials, MLF significantly improved the rate of successful intubation during chest compression compared to without MLF for novice doctors. While intubation time did not significantly differ with or without MLF in the AWS trial, MLF significantly shortened intubation time in McL and McGRATH trials for both novice and experienced doctors. CONCLUSION: These findings suggest that MLF facilitates tracheal intubation with the McL and McGRATH during chest compression.

Evaluation of gum-elastic bougie combined with direct and indirect laryngoscopes in vomitus setting: A randomized simulation trial.

PURPOSE: Videolaryngoscopes may not be useful in the presence of vomitus due to blurred images on the monitor. The objective of our study is to compare the utility of gum-elastic bougie (GEB) application for tracheal intubation with the Macintosh laryngoscope (McL), which is a direct laryngoscope, with that of the Pentax-AWS Airwayscope® (AWS) and McGRATH® MAC (McGRATH) in simulated vomitus settings. METHODS: Sixteen novice doctors performed tracheal intubation on an adult manikin using McL, AWS, and McGRATH with or without GEB under normal and vomitus simulations. RESULTS: In the normal setting the tracheal intubation was successful with the three laryngoscopes regardless of GEB application. In the vomitus setting, the intubation success rate did not significantly improve using McL, while it did using McGRATH or AWS. In the normal settings, GEB application significantly lengthened the intubation time in all three laryngoscopes. By contrast, in the vomitus settings, GEB application significantly shortened the intubation time in all three laryngoscopes. For the comparison of three laryngoscopes, the intubation time did not differ significantly in normal setting, while it was significantly longer in McG and AWS trials than McL trial. CONCLUSION: The GEB application facilitates the tracheal intubation in the vomitus setting using McGRATH and AWS in adult simulation.

Gum-Elastic Bougie Efficacy for Tracheal Intubation During Continuous Chest Compression in Infants-A Crossover Simulation Trial.

BACKGROUND: Recent guidelines for infant cardiopulmonary resuscitation emphasize that all rescuers should minimize interruption of chest compression, even for endotracheal intubation. OBJECTIVE: We compared the utility of application of a gum-elastic bougie (GEB) plus Miller laryngoscope (Mil) with the Mil alone during chest compression on an infant mannequin. METHODS: Sixteen anesthesiologists with more than 2 years of experience performed tracheal intubation on an infant mannequin using the Mil or Mil plus 6Fr GEB, with or without chest compression. Intubation success rate, intubation time, and subjective difficulty scores of laryngoscopy and tube passage through the glottis were measured. RESULTS: In Mil trials, none of the participants failed without compression, whereas four failed with compression (p = 0.03). In Mil-plus-GEB trials, all participants succeeded regardless of chest compression. Intubation time was significantly longer with chest compression in both Mil and Mil-plus-GEB trials (p < 0.001). The intubation time during chest compression was significantly longer in Mil than in Mil-plus-GEB trials (p < 0.001). Difficulty of operation on a visual analog scale (VAS) for laryngoscopy did not significantly differ between Mil and Mil-plus-GEB trials during chest compression, whereas the VAS for tube passage through the glottis was significantly higher in Mil than in Mil-plus-GEB trials. CONCLUSIONS: GEB use shortened the intubation time and improved the success rate of infant tracheal intubation during chest compression by anesthesiologists in simulations.

Needle guides for venous catheter insertion during chest compressions: a crossover simulation trial.

PURPOSE: Recent guidelines for cardiopulmonary resuscitation emphasize that all rescuers should minimize the interruption of chest compressions, even for intravenous access. We assessed the utility of needle guides during ultrasound-guided central venous catheterization (US-CVC) with chest compressions via simulation. METHODS: Twenty-five anesthesiologists with more than 2years of experience performed US-CVC on a manikin with or without a needle guide and with or without chest compressions. Insertion success rate within 2minutes, insertion time, and subjective difficulty of venous puncture or guide wire insertion were measured. RESULTS: In normal trials, 1 participant failed US-CVC without compressions, whereas 6 failed with compressions (P=.04). In needle-guided trials, all participants succeeded without compressions, whereas only 1 failed with compressions (P=.31). Insertion time was significantly longer with chest compressions in both normal and needle-guided trials (P<.001, each). Ultrasound-guided central venous catheterization insertion time in normal trials was significantly longer than in needle-guided trials with compressions (P<.001). Difficulty of operation on a visual analog scale for venous puncture or guide wire insertion was significantly higher in normal trials than in needle-guided trials with compressions. CONCLUSION: Needle guides shortened the insertion time and improved the success rate of US-CVC during chest compressions by anesthesiologists in simulations.

[Significance of Multi-center Obstetrics Perioperative Team Training Including Various Medical Staffs].

We report the development of a multi-center/multispecialist obstetrics perioperative team training program. Participants were members of the team, including anesthesiologists, obstetricians, and operation nurses. A questionnaire survey was conducted prior to course participation to clarify any questions team members had. The courses included a lecture and simulation training with scenario-based discussions or the use of a simulator. Scenarios included massive bleeding during cesarean section, massive bleeding after vaginal delivery, and emergency cesarean section for premature placental abruption. After each course, participants discussed problems associated with obstetrics medical safety in the context of each theme. Simulation-based perioperative team training with anesthesiologists, obstetricians, and operation nurses may serve as a vehicle to promote perioperative obstetrics patient safety.

Tracheal Tube Position Shift During Infant Resuscitation by Chest Compression: A Simulation Comparison by Fixation Method and With or Without Cuff.

BACKGROUND: Tracheal tube placement during infant resuscitation is essential for definite airway protection. Accidental extubation due to tracheal tube displacement is a rare event, but it results in severe complications, especially in infants. OBJECTIVE: The present study evaluated how infant tracheal tube displacement is affected by tape vs. tube holder fixation using a manikin. METHODS: A tracheal tube with internal diameter of 3.5 mm was placed 10 cm from the gum ridge in an advanced life support (ALS) Baby(®) simulator (Laerdal, Stavanger, Norway). In the first trial, cuff pressure was set at 15, 20, and 25 cmH2O and trials were performed at each setting with no fixation, Durapore(®) (3M, St Paul, MN) tape fixation, Multipore(®) (3M) tape fixation, and Thomas(®) Tube Holder (Laerdal) fixation. After 5 min of chest compression, the tracheal tube shift was measured. In the second trial, we compared the tube shift by chest compression with or without cuff in the same way. RESULTS: Relative to no fixation, tracheal tube shift was significantly less in the Durapore, Multipore, and tube holder groups (p < 0.05) at all cuff settings. Of the three fixation methods, the tube holder showed significantly less shift (p < 0.05) relative to tape, regardless of the initial cuff pressure. The positional shift after chest compressions was significantly larger in the trials with cuff than in those without cuff in Durapore or Multipore fixation (p < 0.05), but did not in tube holder fixation. CONCLUSIONS: There is less tracheal tube displacement with tube holder fixation than with tape during continuous infant chest compression simulation. The tube cuff can contribute to the positional shift of the tube during infant chest compression.

Utility of gum-elastic bougie for tracheal intubation during chest compressions in a manikin: a randomized crossover trial.

PURPOSE: The utility of the gum-elastic bougie (GEB) as an assistive device for tracheal intubation during chest compressions has not been sufficiently validated. This study aimed to compare the utility of the GEB during chest compressions on an adult manikin. METHODS: Seventeen novice physicians performed tracheal intubation on an adult manikin using the GEB with or without chest compressions. Intubation success rate, intubation time, subjective difficulty of laryngoscopy, and tube passage through the glottis were measured. P < .05 was considered as significantly different. RESULTS: All novice physicians successfully secured the airway without chest compression with and without the GEB. In contrast, during chest compressions, 7 failed without the GEB, whereas only 1 failed with the GEB (P = .007). Intubation time was significantly longer with chest compressions regardless of GEB use (P < .001). Both laryngoscopy and tube passage through the glottis were perceived as significantly more difficult with chest compressions, regardless of GEB use (P < .001). Subjective difficulty of tube passage through the glottis during chest compression was perceived as significantly more easy by GEB application (P < .001). CONCLUSIONS: These findings suggest that the GEB facilitates tracheal intubation during chest compressions performed by novice physicians in adult simulations.