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Abstract: Insights into the pathophysiology of autoimmune inflammatory diseases including psoriasis have advanced considerably in recent years, and in parallel, so too have the available treatment options. Current clinical paradigms for the treatment of psoriasis have evolved to include targeted biologic therapies, starting with tumour necrosis factor‐alpha (TNF‐α) inhibitors and later, agents targeting interleukin (IL)‐12/23 and IL‐17. The most recent evidence suggests that IL‐23 might be an even more potent target for the effective treatment of psoriasis and other autoimmune inflammatory disorders. This review will describe recent developments leading to the current understanding of the key role of IL‐23 as a ‘master regulator’ of autoimmune inflammation and the clinical evidence for agents that specifically target this modulator in the context of treating psoriasis, spondyloarthropathy and inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: Long-term, real-word data are needed to help manage patients with hidradenitis suppurativa (HS) through this recurrent, painful and debilitating disease., Objectives: To primarily measure real-world effectiveness of adalimumab in HS and to secondarily observe clinical course of HS in the light of patients' response., Methods: In SOLACE, adults with moderate-to-severe HS in need for change in ongoing therapy were treated with adalimumab for up to 52 weeks as per physician's medical practice. Treatment effectiveness was measured by Hidradenitis Suppurativa Clinical Response (HiSCR). Inflammatory nodules, abscesses and draining fistulas were counted, Hurley stage was assessed, and disease severity was rated using the International HS Severity Scoring System (IHS4). A post hoc analysis further explored the HiSCR response by abscess and inflammatory nodule (AN) count at baseline (low, medium and high) and gender. Spontaneously reported safety events were collected., Results: From 23 Canadian centres, 69% of the 138 patients achieved HiSCR at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN counts, respectively. Gender (4 times the odds for female) and age at HS onset (5% decrease with each additional year) had an effect on achieving HiSCR. Treatment with adalimumab led to an important decrease in number of lesions in responders, with most gains observed in inflammatory nodules, more frequently in the lower body area of patients in the high AN count group. The IHS4 scores of responders were substantially lowered, with a larger decrease in patients of the high AN count group. No new safety signal was detected., Conclusions: The effectiveness of adalimumab was maintained during this 1-year period, and an optimal gain was documented for patients with medium and high AN counts. These real-world data support a prompt treatment of HS patients and the use of IHS4 to monitor treatment., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Chronic hand dermatitis is a debilitating inflammatory dermatosis that has a significant impact on the quality of life of those affected. Alitretinoin is an oral retinoid which has proven efficacy and safety in the treatment of chronic hand dermatitis through randomized controlled trials. Real-world evidence, information gathered in the clinic or community setting, as opposed to a research environment, can complement knowledge gained from clinical trials. Herein, real-world evidence supporting the safety and effectiveness of alitretinoin in the management of chronic hand dermatitis will be reviewed., Competing Interests: Melinda Gooderham has been a speaker for Actelion and an investigator, speaker and advisor for Janssen.

Background: OX40 (CD134) is expressed in lesional but not healthy skin of patients with psoriasis. KHK4083 is a fully human monoclonal antibody against OX40., Objective: The primary aim of this first-in-human phase 1 study was to determine the safety and tolerability of ascending single doses of KHK4083 in patients with mild to moderate plaque psoriasis. Secondary aims were to determine the pharmacokinetics and immunogenicity of KHK4083, and an exploratory objective was to assess clinical activity., Methods: In phase 1a, single doses of KHK4083 0.003 and 0.001 mg/kg IV were administered open label in two cohorts (each n = 6). Phase 1b had a multicentre, randomized, double-blind, placebo-controlled, ascending single-dose design in seven cohorts. Randomization was performed 3 : 1 to KHK4083 (n = 6) or placebo (n = 2) within each cohort. Ascending doses of KHK4083 were 0.03, 0.1, 0.3, 1.0, 3.0 and 10 mg/kg IV, and 1.0 mg/kg SC., Results: There were no severe or serious adverse events (AEs), or discontinuations because of AEs. The most frequent treatment-related AEs in the 55 patients who received KHK4083 were mild or moderate chills (9.1%), and infusion/injection site reactions (7.3%). No clinically meaningful or dose-related changes from baseline in laboratory values, vital signs, ECG recordings or physical examinations were observed. Some KHK4083 recipients (10/54) developed anti-KHK4083 antibodies following treatment. Mean elimination half-life (t 1/2 ) increased with dose, maximum serum concentration increased in a dose-proportional manner, and area under the serum concentration-time curve increased in a more than dose-proportional manner with increasing IV dose. Absolute bioavailability following SC administration was 73%. There was some indication of improvement in Psoriasis Area Severity Index (PASI) and sPGA scores at the highest IV doses (1.0 and 10 mg/kg) and the SC dose (1.0 mg/kg). The largest PASI 50 response and improvement in sPGA score ≥2 occurred with KHK4083 1.0 mg/kg SC., Conclusion: KHK4083 administration as a single dose up to 10 mg/kg IV or 1.0 mg/kg SC was generally safe and well tolerated in patients with mild to moderate plaque psoriasis with no dose-limiting AEs., (© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Research suggests that childhood exposure to ultraviolet radiation is a significant risk factor for the development of melanoma and nonmelanoma skin cancers. Sun awareness education programs for children can positively influence children's sun protective practices to decrease the risk of skin cancer., Objective: The purpose of this study was to evaluate a sun awareness education program, entitled "Sun and the Skin" that had recently been developed and implemented in London, Ontario., Method: The study uses a pre- and posttest design to evaluate both knowledge and behaviour of Grade 4 students participating in the program at baseline, immediately after, and 1 month after the program., Results: The students demonstrated a significant increase in their sun-protective practices after participation in the "Sun and the Skin" program. There was a significant improvement in the students' level of knowledge after the program. Improvement in both behaviour and knowledge were maintained weeks after completion of the program. Minor differences in knowledge due to demographic characteristics were detected after the program., Conclusions: A sun awareness education program for Grade 4 students can improve both their knowledge and behaviour over time. This format should be used in conjunction with changes in school policy in order to make a significant longterm impact.

Objective: To report a case of a clarithromycin-associated warfarin interaction and digoxin toxicity in a patient., Case Summary: A 72-year-old white woman with chronic atrial fibrillation receiving long-standing therapy with digoxin 0.25 mg/d and warfarin 22.5 mg/wk was prescribed clarithromycin 500 mg three times daily for eradication of Helicobacter pylori. The patient presented to the emergency department with gastrointestinal symptoms, weakness, dizziness, and visual changes 12 days after initiation of clarithromycin. Laboratory results revealed a serum digoxin concentration of 4.6 ng/mL (normal 1.0-2.6) and an international normalized ratio of 7.3 (2.0-3.0). Digoxin, warfarin, and clarithromycin were discontinued and the patient was admitted to the hospital for treatment to resolve the symptoms and to return laboratory values to a safe range. Reduced dosages of digoxin (0.125 mg/d) and warfarin (17.5 mg/wk) were restarted on day 7 of hospitalization. The patient was discharged on day 11 in good condition., Discussion: Several reports of clarithromycin-induced drug interactions with digoxin and with warfarin have been published. Previously, case reports of macrolide-associated interactions mainly involved erythromycin, but more recently have implicated clarithromycin. The interaction between clarithromycin and warfarin is thought to occur from an inhibition of the cytochrome P450 drug metabolizing system. Clarithromycin is thought to cause digoxin toxicity by an alteration of the digoxin-metabolizing gut flora, thereby causing an increase in the digoxin concentration in susceptible individuals. Drug interactions can occur by different mechanisms in the same patient., Conclusions: Potential drug interactions can occur between commonly prescribed medications. It is important to monitor patients for symptoms and alterations in laboratory values to prevent not only serious complications, but also unnecessary hospitalizations.

Background: Physicians teach sun awareness to their patients, but frequently have no formal training in this area. A week-long dermatology curriculum during Sun Awareness Week that included skin cancer and sun awareness education to first-year medical students was introduced in May 1998 at the University of Western Ontario, London, Canada., Objective: The purpose of this study was to determine the baseline knowledge, attitudes, and behaviour of the first-year medical students towards sun awareness before and after the new curriculum., Method: This study used a pre- and post-test design to determine the impact of the curriculum on the medical students' knowledge, attitudes, and intent to change behaviour. It also reports any influence of demographic variables on these parameters., Results: The students demonstrated a substantial improvement in their knowledge of sun-related topics despite some baseline knowledge. Many students reported unhealthy behaviour prior to the curriculum, but demonstrated an intent to adopt more healthy behaviour after the curriculum. Minor differences in knowledge and behaviour due to demographic characteristics disappeared upon completion of the curriculum., Conclusions: An undergraduate medical curriculum with skin cancer and sun awareness education can improve the medical students' knowledge, attitudes, and behaviour towards sun awareness.

A gas chromatographic-mass spectrometric assay has been developed for the measurement of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in food. Stable isotope-labelled analogues of MeIQx and PhIP are used as internal standards and the synthesis of deuterated PhIP is described. The mass spectrometer is operated in the electron-capture negative ion chemical ionisation mode and the amines are chromatographed as their di-3,5-bistrifluoromethylbenzyl derivatives. All three compounds can be measured in a single chromatographic run and detection limits of 0.05, 0.1 and 0.2 ng/g for MeIQx, DiMeIQx and PhIP, respectively, in food are obtained. Various home-cooked and commercially prepared foodstuffs were analysed with this assay and several were found to contain measurable amounts of one or more of the three amines. These results are presented and discussed.