Real-world experience of dupilumab treatment for atopic dermatitis in adults: a retrospective analysis of patients' records.

BACKGROUND: Clinical trial data for dupilumab, a monoclonal antibody against the interleukin-4 receptor (IL-4Rα), have shown that it is safe and effective for the treatment of moderate to severe atopic dermatitis in patients whose disease is resistant to other therapies. However, little real-world experience with dupilumab use has been reported thus far. The aim of this retrospective study was to assess overall outcomes in adult patients with atopic dermatitis (AD) treated with dupilumab. METHODS: A retrospective review of electronic medical records was conducted for patients treated with dupilumab in the Department of Dermatology at the University of California, Irvine. RESULTS: We analyzed the medical records of 77 AD patients who received dupilumab according to standard dosing and had at least one documented follow-up visit. In 66 patients (86%), dupilumab improved clinical disease severity, with 23 patients (30%) experiencing complete clearance on dupilumab. Dupilumab was generally well-tolerated and caused no serious adverse events. The most common side effects included dry eyes, conjunctivitis, and keratitis. The most common reason for discontinuation of treatment was lack of substantial clinical improvement or progression of disease severity, followed by ophthalmologic side effects. CONCLUSIONS: Overall, dupilumab was well-tolerated and resulted in clinical improvement in our patient population. These results provide additional important information on the safety and utility of dupilumab treatment for moderate to severe atopic dermatitis in the real-world clinical setting.

Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody-negative pemphigus vulgaris.

Pemphigus vulgaris (PV) is a potentially lethal mucocutaneous blistering disease characterized by IgG autoantibodies (AuAbs) binding to epidermal keratinocytes and inducing this devastating disease. Here, we observed that non-desmoglein (Dsg) AuAbs in the sera of patients with Dsg1/3 AuAb-negative acute PV are pathogenic, because IgGs from these individuals induced skin blistering in neonatal mice caused by suprabasal acantholysis. Serum levels of AuAbs to desmocollin 3 (Dsc3), M3 muscarinic acetylcholine receptor (M3AR), and secretory pathway Ca2+/Mn2+-ATPase isoform 1 (SPCA1) correlated with the disease stage of PV. Moreover, AuAb absorption on recombinant Dsc3, M3AR, or SPCA1 both prevented skin blistering in the passive transfer of AuAbs model of PV in BALB/c mice and significantly decreased the extent of acantholysis in a neonatal mouse skin explant model. Although acantholytic activities of each of these immunoaffinity-purified AuAbs could not induce a PV-like phenotype, their mixture produced a synergistic effect manifested by a positive Nikolskiy sign in the skin of neonatal mice. The downstream signaling of all pathogenic non-Dsg AuAbs involved p38 mitogen-activated protein kinase (MAPK)-mediated phosphorylation and elevation of cytochrome c release and caspase 9 activity. Anti-Dsc3 and anti-SPCA1 AuAbs also activated SRC proto-oncogene, nonreceptor tyrosine kinase (SRC). Of note, although a constellation of non-Dsg AuAbs apparently disrupted epidermal integrity, elimination of a single pathogenic AuAb could prevent keratinocyte detachment and blistering. Therefore, anti-Dsg1/3 AuAb-free PV can be a model for elucidating the roles of non-Dsg antigen-specific AuAbs in the physiological regulation of keratinocyte cell-cell adhesion and blister development.

Effect of dyad training on medical students' cardiopulmonary resuscitation performance.

We investigated the effects of dyadic training on medical students' resuscitation performance during cardiopulmonary resuscitation (CPR) training.We provided students with a 2-hour training session on CPR for simulated cardiac arrest. Student teams were split into double groups (Dyad training groups: Groups A and B) or Single Groups. All groups received 2 CPR simulation rounds. CPR simulation training began with peer demonstration for Group A, and peer observation for Group B. Then the 2 groups switched roles. Single Groups completed CPR simulation without peer observation or demonstration. Teams were then evaluated based on leadership, teamwork, and team member skills.Group B had the highest first simulation round scores overall (P = 0.004) and in teamwork (P = 0.001) and team member skills (P = 0.031). Group B also had the highest second simulation round scores overall (P < 0.001) and in leadership (P = 0.033), teamwork (P < 0.001), and team member skills (P < 0.001). In the first simulation, there were no differences between Dyad training groups with those of Single Groups in overall scores, leadership scores, teamwork scores, and team member scores. In the second simulation, Dyad training groups scored higher in overall scores (P = 0.002), leadership scores (P = 0.044), teamwork scores (P = 0.005), and team member scores (P = 0.008). Dyad training groups also displayed higher improvement in overall scores (P = 0.010) and team member scores (P = 0.022).Dyad training was effective for CPR training. Both peer observation and demonstration for peers in dyad training can improve student resuscitation performance.

Using multimedia tools and high-fidelity simulations to improve medical students' resuscitation performance: an observational study.

OBJECTIVES: The goal of our study was to shed light on educational methods to strengthen medical students' cardiopulmonary resuscitation (CPR) leadership and team skills in order to optimise CPR understanding and success using didactic videos and high-fidelity simulations. DESIGN: An observational study. SETTING: A tertiary medical centre in Northern Taiwan. PARTICIPANTS: A total of 104 5-7th year medical students, including 72 men and 32 women. INTERVENTIONS: We provided the medical students with a 2-hour training session on advanced CPR. During each class, we divided the students into 1-2 groups; each group consisted of 4-6 team members. Medical student teams were trained by using either method A or B. Method A started with an instructional CPR video followed by a first CPR simulation. Method B started with a first CPR simulation followed by an instructional CPR video. All students then participated in a second CPR simulation. OUTCOME MEASURES: Student teams were assessed with checklist rating scores in leadership, teamwork and team member skills, global rating scores by an attending physician and video-recording evaluation by 2 independent individuals. RESULTS: The 104 medical students were divided into 22 teams. We trained 11 teams using method A and 11 using method B. Total second CPR simulation scores were significantly higher than first CPR simulation scores in leadership (p<0.001), teamwork (p<0.001) and team member skills (p<0.001). For methods A and B students' first CPR simulation scores were similar, but method A students' second CPR simulation scores were significantly higher than those of method B in leadership skills (p=0.034), specifically in the support subcategory (p=0.049). CONCLUSIONS: Although both teaching strategies improved leadership, teamwork and team member performance, video exposure followed by CPR simulation further increased students' leadership skills compared with CPR simulation followed by video exposure.

Why we do caesars: a comparison of the trends in caesarean section delivery over a decade.

INTRODUCTION: In the United Kingdom, caesarean section (CS) rates have increased from 9% of deliveries in 1980 to 21% in 2001. A similar increase in CS rates has been seen in many developed countries. This is beyond the World Health Organisation's (WHO's) recommended level of 15%. This is a worrying trend as the risks of placenta previa, placenta accreta, hysterectomies, bladder and bowel injuries are increased with subsequent CS. We aim to ascertain the commonest indications for CS in a tertiary hospital and make recommendations to decrease future CS rates. MATERIALS AND METHODS: This retrospective analysis compares the 5 most common indications for CS in 1999 and 2009. CS rates in the 2 study periods are tabulated and analysed as well. RESULTS: In the first study period between January and December 1999, there were 2048 deliveries of which 365 were via CS. In the second study period of a decade later from January to December 2009, there were 1572 deliveries of which 531 were via CS. This gives an increase in CS rate from 17.8% in 1999 to 34% in 2009. The main indications for CS in 1999 were: cephalopelvic disproportion (18.6%), breech (14.2%), non-reassuring fetal status (11.8%), 1 previous CS (11.2%) and pregnancy-induced hypertension/pre-eclampsia/eclampsia (6.6%). The main indications for CS in 2009 were: 1 previous CS (18.1%), non-reassuring fetal status (12.2%), cephalopelvic disproportion (10.5%), 2 or more previous CS (7.9%) and breech (7.7%). CONCLUSION: There is a significant increase in CS rates over the last decade with an increased percentage of CS done because of a previous CS. This is associated with increased risk of complications as well. Recommendations are suggested with the view to decrease future CS rates.