Greater mechanistic understanding of the cutaneous pathogenesis of Stevens-Johnson syndrome/toxic epidermal necrolysis can shed light on novel therapeutic strategies: a comprehensive review.

PURPOSE OF REVIEW: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (SCARs) characterized by widespread epithelial detachment and blistering, which affects the skin and mucocutaneous membranes. To date, therapeutic interventions for SJS/TEN have focused on systematic suppression of the inflammatory response using high-dose corticosteroids or intravenous immunoglobulin G (IgG), for example. No targeted therapies for SJS/TEN currently exist. RECENT FINDINGS: Though our understanding of the pathogenesis of SJS/TEN has advanced from both an immunological and dermatological perspective, this knowledge is yet to translate into the development of new targeted therapies. SUMMARY: Greater mechanistic insight into SJS/TEN would potentially unlock new opportunities for identifying or repurposing targeted therapies to limit or even prevent epidermal injury and blistering.

TNF-α induced extracellular release of keratinocyte high-mobility group box 1 in Stevens-Johnson syndrome/toxic epidermal necrolysis: Biomarker and putative mechanism of pathogenesis.

Decreased epidermal high-mobility group box 1 (HMGB1) expression is an early marker of epidermal injury in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Etanercept, an anti-tumor necrosis factor therapeutic, is effective in the treatment of SJS/TEN. The objective was to characterize antitumor necrosis factor-alpha (TNF-α)-mediated HMGB1 keratinocyte/epidermal release and etanercept modulation. HMGB1 release from TNF-α treated (± etanercept), or doxycycline-inducible RIPK3 or Bak-expressing human keratinocyte cells (HaCaTs) was determined by western blot/ELISA. Healthy skin explants were treated with TNF-α or serum (1:10 dilution) from immune checkpoint inhibitor-tolerant, lichenoid dermatitis or SJS/TEN patients ± etanercept. Histological and immunohistochemical analysis of HMGB1 was undertaken. TNF-α induced HMGB1 release in vitro via both necroptosis and apoptosis. Exposure of skin explants to TNF-α or SJS/TEN serum resulted in significant epidermal toxicity/detachment with substantial HMGB1 release which was attenuated by etanercept. Whole-slide image analysis of biopsies demonstrated significantly lower epidermal HMGB1 in pre-blistered SJS/TEN versus control (P < 0.05). Keratinocyte HMGB1 release, predominantly caused by necroptosis, can be attenuated by etanercept. Although TNF-α is a key mediator of epidermal HMGB1 release, other cytokines/cytotoxic proteins also contribute. Skin explant models represent a potential model of SJS/TEN that could be utilized for further mechanistic studies and targeted therapy screening.

Factors impeding the supply of over-the-counter medications according to evidence-based practice: A mixed-methods study.

OBJECTIVE: Despite the positive attitudes pharmacists have toward evidence-based practices (EBPs), its application in community pharmacies in Saudi Arabia is lacking. Therefore, this study aimed to explore and assess EBPs by community pharmacists in Saudi Arabia when they dispense over-the-counter (OTC) medications for three minor ailments: diarrhea, cough, and the common cold. RESEARCH DESIGN AND METHODS: We used a mixed-methods approach consisting of two study parts. The first was a quantitative investigation that used mystery shoppers. Four researchers, posing as mystery shoppers, visited 214 randomly selected pharmacies in the Riyadh region of Saudi Arabia. They used 14 questions from a standardized checklist to examine EBPs by community pharmacists. The qualitative part of the study entailed three focus-group discussions with 13 pharmacists from different community practice settings and explored factors that affected the application of EBPs when supplying OTC medications from the pharmacists' point of view. RESULTS: The analysis indicated that 40% of pharmacists dispensed OTC medications according to EBPs. Logistic regression analysis showed that one question, "Describe your symptoms", predicted the correct supply of OTC medications (p = 0.021). The qualitative section of the study identified nine factors that affected EBP. Some of these factors facilitated EBP, such as established patient-pharmacist relationships, some acted as barriers such as conflicts between available evidence, while other factors could either facilitate or hinder EBPs, such as the health literacy of the patient. CONCLUSION: Given that dispensing OTC medication is a core function of pharmacists, this study uncovered low adherence to EBPs by community pharmacists in Saudi Arabia when dispensing OTC medication for three minor ailments: diarrhea, cough, and the common cold. Furthermore, this study identified a number of explanatory factors for this low adherence. Targeting these factors could help change the behavior of pharmacists and decrease undesirable outcomes.

Analysis of medication errors at a large tertiary care hospital in Saudi Arabia: a retrospective analysis.

Background Medication errors (MEs) are common in health care settings and pose a threat for the hospitalized population. Therefore, aspects of MEs were explored in a tertiary setting serving a diverse population. Objective To examine the occurrence, severity and reporting of MEs in hospitalized patients. Methods This retrospective analysis included 10,683 ME report forms that were received by the Medication Safety Unit of King Saud Medical City (KSMC) in 2015. ME outcomes were determined according to the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Index for categorizing MEs algorithm. Results A total of 13,677 MEs in 912,500 prescriptions were reported. The incidence rate of MEs was 1.5% (13,677/912,500). The highest percentage (42.2%) of MEs occurred during the transcription stage, and 70.0% of MEs were reported as near misses. Wrong frequency and wrong concentration accounted for nearly half of the MEs. Conclusion We found 1.5 MEs per 100 prescriptions; more than two-thirds of the MEs were preventable and were intercepted before reaching the patients. Most MEs reported by pharmacists occurred at the transcription stage while wrong frequency was the most common error type encountered. Further studies should explore the clinical consequences of MEs at a healthcare institution.