Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Skin delivery is an exciting and challenging field. It is a promising approach for effective drug delivery due to its ease of administration, ease of handling, high flexibility, controlled release, prolonged therapeutic effect, adaptability, and many other advantages. The main associated challenge, however, is low skin permeability. The skin is a healthy barrier that serves as the body's primary defence mechanism against foreign particles. New advances in skin delivery (both topical and transdermal) depend on overcoming the challenges associated with drug molecule permeation and skin irritation. These limitations can be overcome by employing new approaches such as lipid nanosystems. Due to their advantages (such as easy scaling, low cost, and remarkable stability) these systems have attracted interest from the scientific community. However, for a successful formulation, several factors including particle size, surface charge, components, etc. have to be understood and controlled. This review provided a brief overview of the structure of the skin as well as the different pathways of nanoparticle penetration. In addition, the main factors influencing the penetration of nanoparticles have been highlighted. Applications of lipid nanosystems for dermal and transdermal delivery, as well as regulatory aspects, were critically discussed.

BackgroundCatastrophic antiphospholipid syndrome (CAPS) is characterized by the rapid onset of widespread or multifocal large and/or small vessel thrombosis associated with multi-organ failure in patients meeting the serological criteria for antiphospholipid syndrome [1]. Mortality in CAPS approaches 50% [2].ObjectivesThe RARE-BestPractices project group identified CAPS as a rare disease condition of interest in which to develop a clinical practice guideline. The project was run in partnership with McMaster University, and used the GIN-McMaster Guideline Development checklist and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to develop guidelines on rare diseases [3].MethodsThe CAPS guideline was coordinated by a steering committee including representatives from RARE-BP and methodologists from McMaster University. The CAPS guideline panel consisted of 19 international members, including patient representation. The panel used the GradePro software to brainstorm and prioritize potential questions and outcomes. Systematic reviews were performed for each question. To supplement the published evidence, we compiled raw data for mortality from the CAPS Registry, and systematically elicited expert opinion from the panel members using a systematic observation form. For each question an evidence profile and evidence to decision table was generated and shared.ResultsThe question prioritization step generated 47 questions, which were ranked to identify the top priorities. The top 10 questions were chosen for guideline development, yielding 7 therapy and 3 diagnostic questions. The outcome generation step yielded 7 outcomes.The questions were addressed during an in-person panel meeting, held on April 27, 2016 in Barcelona, Spain, with follow-up via webinar on June 3, 2016, and with web-based voting completed July 31, 2016.Recommendations were developed for all questions and will be discussed in detail.ConclusionsTen recommendations were issued by the CAPS Guideline Panel to assist clinicians in diagnosis and management of suspected CAPS patients. Future research is needed to improve evidence quality in rare diseases such as CAPS. The GIN-McMaster Guideline Development Checklist and the GRADE methodology were effective in producing a rigorous guideline in this rare disease.References Asherson R. The catastrophic antiphospholipid syndrome. J Rheumatol 1992.Cervera R, Bucciarelli S, Plasín M, et al. Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the “CAPS Registry”. J Autoimmun 2009;32:240–5.Guyatt G, Oxman A, Vist G, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924–6. Disclosure of InterestNone declared