8 research outputs found
Understanding the experience of ethnic tourism from the needs of domestic and international tourists: A case study of Sade Rembitan, Indonesia
No full textThe case study of this research is Sade Rembitan, one of the only two ethnic villages on Lombok still inhabited by its original people, and which has been increasingly promoted as a tourist attraction and instrument to improve welfare for ethnic communities. Since different tourist groups may differ in the experience they seek in an ethnic tourism destination, it is important for a destination to understand how tourists are likely to respond to their products and to contribute to a profitable and successful attraction. The goal of this research is to investigate how to offer a more successful ethnic tourist experience to both domestic and international tourists, in the context of a fast-growing tourism destination. The research is based on the concept of ethnic tourism and its elements. By using desk research, observations, unstructured interviews, questionnaires, photography and semi-structured interviews, the research has been divided into three phases: the context and problem statement, the measurement of the tourist experience and differences between nationalities and finally the deeper understanding of the difference in tourist experience. The analysis reveals that the tourist experience in Sade Rembitan indeed differs for the domestic and international tourist. Indonesian tourists rate the overall tourist experience higher than international tourists. The gap seems to arise from the missing element of the experience of activities, which is seen as a crucial element in an ethnic tourism experience. For the international tourist, there is a need for more interaction, a mediator between the visitor and local community and to become part of the real lifestyle; something that is currently missing in Sade Rembitan
Effective interventions for micro and small enterprises to reach the preferable future of the Canggu area in Bali
No full textAs tourist arrivals to Bali have increased steadily over the past 40 years, the crowds from Kuta and
Seminyak have started to shift towards the now booming area of Canggu. Rapid developments
present the community with the challenge of preservation vs. economic growth that will impact
the destination’s future. The objective of this study is to assess, analyze and evaluate the present
and future situation of the Canggu area in order to give advice on the match between the area's
supply and demand. The study provides Micro and Small Enterprises (MSEs) with
recommendations on effective interventions in order to strengthen their strategic position to
achieve the destination’s preferable future. This study used four different research methods: desk
research, participant observations, surveys with tourists, and semi-structured interviews with
enterprises. Results show that the most impactful difference between MSEs lies in the level of
strategy refinement, which suggests that creating a circular model between MSEs could
strengthen the area of Canggu
Corresponding author. Tel.: 41-22-76-73788; fax.: 41-22-76-73394.
No full textHybrid assemblies of LHC1 read-out chips and 300 #m thick silicon pixel detectors have been tested with a 120 GeV/c pion beam at the CERN SPS. The equivalent noise charge at the input of the preampli"er is &200 e#. The particle detection eciency plateau is reached for a 60 ns wide trigger pulse applied after a &2 #s delay. The 50 #m#50 #m pixels yield a spatial precision of #"129.40.2 #m in the large pitch direction. In the other direction the precision is #"12.20.2 #m for single-pixel clusters and #"8.20.2 #m for double-pixel clusters, yielding an average of #"11.40.2 #m. Three di!erent detector layouts on the same pitch were characterized. # 2000 Elsevier Science B.V. All rights reserved
Strange baryon production in Pb-Pb collisions at 158 GeV/c
No full textDocument engineering considers content as a recorded resource on one hand and several dynamically computed views on the other. Since the resource as such is inaccessible and views are multiple and unordered, we argue that content objectivity is lost and document as such disappears. We propose to consider published views as a folder or a collection in which author and reader can navigate by the means of a particular and conventional view, the canonical form, that constitutes an objective reference for the content
Strange baryon production in Pb-Pb collisions at 158 GeV/c
No full textDocument engineering considers content as a recorded resource on one hand and several dynamically computed views on the other. Since the resource as such is inaccessible and views are multiple and unordered, we argue that content objectivity is lost and document as such disappears. We propose to consider published views as a folder or a collection in which author and reader can navigate by the means of a particular and conventional view, the canonical form, that constitutes an objective reference for the content
Strange baryon production in Pb-Pb collisions at 158 GeV/c
No full textDocument engineering considers content as a recorded resource on one hand and several dynamically computed views on the other. Since the resource as such is inaccessible and views are multiple and unordered, we argue that content objectivity is lost and document as such disappears. We propose to consider published views as a folder or a collection in which author and reader can navigate by the means of a particular and conventional view, the canonical form, that constitutes an objective reference for the content
Off-Label Combination Therapies for the Management of Atopic Dermatitis: A Protocol for a Scoping Review
No full textIntroduction:
Atopic dermatitis (AD) is a chronic, heterogeneous and relapsing inflammatory skin disease that presents a significant global health burden, affecting up to 20% of the paediatric population and 2-10% of adults worldwide.1–3 AD is considered the skin disease with the highest non-fatal health burden due to its profound negative impact on patient quality of life, sleep and mental health.1,4–6 AD is characterised by severe pruritus and xerosis, the pathogenesis of which is multifactorial, including an interplay between genetic predisposition, immune dysregulation with aberrant Th2 responses, skin barrier disruption and cutaneous dysbiosis; each of which may be modulated by environmental factors.2,7 These cytokines play a central role in B-cell maturation, IgE class switching and the down-regulation of essential skin barrier proteins such filaggrin, loricrin and involucrin.8
Current Therapeutic Landscape:
The current management of AD follows a step-wise approach based on disease severity.9 For mild forms, the cornerstone of therapy includes trigger avoidance, regular use of emollients to combat xerosis and the application of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI).9 However, patients with moderate-to-severe disease that remains recalcitrant to topical interventions often require second-line treatments, including phototherapy or systemic immunomodulatory agents.5,9
Historically, systemic options were limited to conventional immunosuppressants such as ciclosporin A (CsA), methotrexate (MTX), azathioprine (AZA) and mycophenolate mofetil (MMF).10,11 Despite extensive clinical experience for use in management of moderate-severe AD, the above therapies are not licensed by the FDA/EMA/Japan for management of moderate to severe AD. Their long-term application is often curtailed by an unfavourable risk-benefit ratio, potential organ toxicity (e.g., nephrotoxicity with CsA or bone-marrow suppression with MTX), and a lack of robust long-term data.10,12
The therapeutic landscape was revolutionised in 2017 with the approval of dupilumab, the first biologic targeting the IL-4 receptor alpha chain to inhibit the signalling of IL-4 and IL-13.13 Since then the therapeutic landscape has expanded to include other biologics such as lebrikizumab, nemolizumab and tralokinumab, as well as oral small molecule drugs such as Janus kinase (JAK) inhibitors (e.g., abrocitinib, baricitinib, and upadacitinib).14 Despite these advancements, a subset of patients, demonstrates an inadequate response or resistance to biologic monotherapy.14,15
The Challenge of Recalcitrant Disease and Off-Label Combinations:
In clinical practice, dermatologists often encounter patients whose disease is not adequately controlled by a single systemic agent.16 While phase III clinical trials typically evaluate these drugs as monotherapy (or with limited TCS use), daily practice sometimes involves an off-label combination of systemic therapies.1,3,17
There are two primary clinical scenarios where these combinations occur:
1. Transitioning and tapering: patients starting a new biologic like dupilumab may continue a conventional immunosuppressant (such as CsA) for several weeks to prevent disease flares during the transition period or to induce faster clinical remission.18
2. Rescue therapy: In patients experiencing a lack of response or loss of disease control on biologic monotherapy, a second systemic agent or phototherapy may be added as a "rescue" or ‘combination’ strategy to enhance effectiveness and maintain long-term control.3
Observational data indicate that up to 45% of patients in real-world settings may continue systemic immunosuppressants during the initiation of dupilumab.1 Common combinations reported in the literature include dupilumab paired with methylprednisolone, ciclosporin, methotrexate or azathioprine.3
Rationale for a Scoping Review:
Despite the increasing use of combined systemic regimens, there is neither standardized guidelines nor comprehensive evidence mapping regarding their safety and effectiveness.3 Most clinical trials exclude patients with complex histories of multiple systemic failures, meaning trial data may not reflect real-world effectiveness in the most severe patients.1 While some studies suggest that combining dupilumab with conventional drugs can be an effective and safe way to transition to monotherapy or salvage treatment, these findings are often limited by small sample sizes, retrospective designs, and short follow-up durations.1,3 With ongoing expansion of the therapeutic armamentarium for management of moderate-severe AD, this adds further complexity to potential combination strategies.5,7 As such, a scoping review is necessary to map the existing literature on the off-label use of combination systemic therapies for AD. By synthesizing data from available studies, this protocol aims to clarify the evidence base and identify critical research gaps that must be addressed to optimise personalised management for patients with recalcitrant AD.
Objective:
The primary objective of this scoping review is to identify and map the evidence concerning the off-label use of combination systemic therapies in the treatment of moderate-to-severe atopic dermatitis in adults and children. This review will identify the types of combinations currently utilised, the clinical rationales for their use (e.g., rescue/combination vs. bridging), and the reported outcomes regarding physician-rated severity, patient-reported outcome measures, and safety concerns.
Methods and Analysis
Search strategy:
A comprehensive electronic search of MEDLINE, the Cochrane Library, and Web of Science will be conducted from database inception to January 2026. The search strategy will combine controlled vocabulary (i.e. MeSH terms) and free-text keywords relating to atopic dermatitis and systemic therapies, including but not limited to: systemic therapy, immunosuppressive agent, atopic dermatitis, eczema, methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, abrocitinib, baricitinib, dupilumab, tralokinumab, lebrikizumab, nemolizumab, and upadacitinib. Synonyms and alternative spellings will be incorporated as appropriate.
The search will not be restricted by language; however, studies will only be included if an English translation is available, either locally or through artificial intelligence–assisted translation. Reference lists of included studies will be hand-searched to identify additional relevant publications. Corresponding authors of included studies will be contacted where necessary to identify further published or unpublished data relevant to the review question.
Grey literature will be searched by reviewing published online abstracts from the British Association of Dermatologists Annual Scientific Meeting, American Academy of Dermatology Annual Meeting, and the European Academy of Dermatology and Venereology Biannual Symposium and Congress.
Draft search strategy:
(systemic therapy OR immunosuppressive agent) AND (atopic dermatitis OR eczema) AND (methotrexate OR cyclosporine OR azathioprine OR mycophenolate mofetil OR abrocitinib OR baricitinib OR dupilumab OR tralokinumab OR lebrikizumab OR nemolizumab OR upadacitinib)
Types of studies to be included:
Experimental and observational study designs will be eligible, including randomised controlled trials, cohort studies, case–control studies, cross-sectional studies, and case series.
Condition or domain being studied:
This scoping review will examine the off-label use of combination systemic therapies for the management of moderate-severe atopic dermatitis. Currently, there are no head-to-head trials evaluating the efficacy of different combinations of systemic treatments, and evidence in this area remains limited. Despite this, anecdotal reports suggest such combinations are commonly used in patients with severe or treatment-refractory disease.
Participants or population:
Children and adults aged 0–99 years with a diagnosis of atopic dermatitis made by a medical practitioner will be eligible. Participants must be receiving at least one systemic agent for the management of atopic dermatitis. Studies from all geographical regions and both hospital and community settings will be included.
Interventions and exposures:
Combination systemic therapies used for the management of atopic dermatitis.
Comparator:
Single-agent systemic therapy or standard systemic treatment where applicable.
Outcomes:
Primary outcome
Efficacy of combination systemic therapies in the management of atopic dermatitis.
Secondary outcomes
• Identification of the most effective combination systemic therapies
• Safety and tolerability of combination systemic therapies in patients with atopic dermatitis.
Risk of bias:
The Joanna Briggs Institute (JBI) critical appraisal tools will be used to assess methodological quality and risk of bias for cohort, case–control, cross-sectional, and case series studies. The Cochrane Risk of Bias tool will be used for randomised controlled trials.
Eligibility criteria:
Inclusion criteria
• Studies including male and/or female participants aged 0–99 years with atopic dermatitis.
• Participants receiving systemic therapy for the management of atopic dermatitis.
Exclusion criteria:
• Studies in which participants are not treated with systemic agents.
• Studies for which no English-language translation is available.
Study selection:
Two reviewers will independently screen titles and abstracts for eligibility. Full-text articles will be obtained for any study deemed potentially relevant by either reviewer. Full-text screening will be conducted independently by both reviewers. Disagreements will be resolved through discussion or adjudication by a third reviewer if necessary.
Data extraction:
Two reviewers will independently chart data from included studies using a standardised data extraction form. Discrepancies will be resolved by reference to the original publication. Where applicable, studies published in languages other than English will be assessed and data extracted using AI-assisted translation tools. Additional information will be sought from study authors when required.
Data will be managed using scoping review software such as Covidence and will include:
• Author(s)
• Year of publication
• Country of origin
• Study aims
• Population characteristics and sample size
• Study design and methodology
• Details of interventions and comparators (including duration)
• Outcomes and outcome measures
• Key findings relevant to the review question
Data extraction will be iterative, with any modifications documented and reported in the final review.
Data synthesis:
Included studies will be analysed descriptively to map the characteristics and extent of existing literature. Results will be summarised narratively and presented in tables and charts as appropriate. As a scoping review, the emphasis will be on mapping the breadth of evidence rather than synthesising effect estimates or drawing conclusions regarding efficacy.
Subgroup analysis:
Where sufficient data are available, subgroup analyses may be undertaken to explore heterogeneity, including:
• Age group (paediatric vs adult)
• Type of systemic therapy combination
• Conventional immunosuppressant plus biologic vs biologic plus JAK inhibitor
• Disease severity
Ethics and dissemination:
As this study involves the analysis of publicly available data, ethical approval is not required. Findings will be disseminated through publication in a peer-reviewed medical journal and presentation at relevant scientific meetings.
References:
1. Wijs LEM, Bosma AL, Erler NS, Hollestein LM, Gerbens LAA, Middelkamp‐Hup MA, et al. Effectiveness of dupilumab treatment in 95 patients with atopic dermatitis: daily practice data. Br J Dermatol. 2020 Feb;182(2):418–26.
2. Calabrese G, Licata G, Gambardella A, De Rosa A, Alfano R, Argenziano G. Topical and Conventional Systemic Treatments in Atopic Dermatitis: Have They Gone Out of Fashion? Dermatol Pract Concept. 2022 Feb 2;e2022155.
3. Gori N, Chiricozzi A, Malvaso D, D’Urso DF, Caldarola G, De Simone C, et al. Successful Combination of Systemic Agents for the Treatment of Atopic Dermatitis Resistant to Dupilumab Therapy. Dermatology. 2021;237(4):535–41.
4. Drucker AM, Ellis AG, Bohdanowicz M, Mashayekhi S, Yiu ZZN, Rochwerg B, et al. Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis: A Systematic Review and Network Meta-analysis. JAMA Dermatol. 2020 June 1;156(6):659.
5. Drucker AM, Lam M, Prieto-Merino D, Malek R, Ellis AG, Yiu ZZN, et al. Systemic Immunomodulatory Treatments for Atopic Dermatitis: Living Systematic Review and Network Meta-Analysis Update. JAMA Dermatol. 2024 Sept 1;160(9):936.
6. Fasseeh AN, Elezbawy B, Korra N, Tannira M, Dalle H, Aderian S, et al. Burden of Atopic Dermatitis in Adults and Adolescents: a Systematic Literature Review. Dermatol Ther. 2022 Dec;12(12):2653–68.
7. Silverberg JI, Hong HC ho, Calimlim BM, Lee WJ, Teixeira HD, Collins EB, et al. Comparative Efficacy of Targeted Systemic Therapies for Moderate-to-Severe Atopic Dermatitis without Topical Corticosteroids: An Updated Network Meta-analysis. Dermatol Ther. 2023 Oct;13(10):2247–64.
8. Furue M. Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis. Int J Mol Sci. 2020 July 29;21(15):5382.
9. Wollenberg A, Kinberger M, Arents B, Aszodi N, Barbarot S, Bieber T, et al. European Guideline ( EUROGUIDERM ) on atopic eczema: Living update. J Eur Acad Dermatol Venereol. 2025 Sept;39(9):1537–66.
10. Drucker AM, Eyerich K, De Bruin-Weller MS, Thyssen JP, Spuls PI, Irvine AD, et al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018 Mar;178(3):768–75.
11. Frampton JE, Blair HA. Dupilumab: A Review in Moderate-to-Severe Atopic Dermatitis. Am J Clin Dermatol. 2018 Aug;19(4):617–24.
12. Simpson EL, Bruin-Weller M, Flohr C, Ardern-Jones MR, Barbarot S, Deleuran M, et al. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol. 2017 Oct;77(4):623–33.
13. Van Der Schaft J, Thijs JL, De Bruin-Weller MS, Balak DMW. Dupilumab after the 2017 approval for the treatment of atopic dermatitis: what’s new and what’s next? Curr Opin Allergy Clin Immunol. 2019 Aug;19(4):341–9.
14. Silverberg JI, Bieber T, Paller AS, Beck L, Kamata M, Puig L, et al. Lebrikizumab vs Other Systemic Monotherapies for Moderate-to-Severe Atopic Dermatitis: Network Meta-analysis of Efficacy. Dermatol Ther. 2025 Mar;15(3):615–33.
15. Wu JJ, Lafeuille MH, Emond B, Fakih I, Duh MS, Cappelleri JC, et al. Real-World Effectiveness of Newly Initiated Systemic Therapy for Atopic Dermatitis in the United States: A Claims Database Analysis. Adv Ther. 2022 Sept;39(9):4157–68.
16. Zhang L, Peng G, Wang M, Niyonsaba F, Gao X. Beyond the blockade: unmet needs in systemic targeted atopic dermatitis therapy. Front Immunol. 2025 Nov 27;16:1712757.
17. Strizzolo R, Seneschal J, Soria A, Staumont-Sallé D, Barbarot S, Viguier M, et al. Real-life management of atopic dermatitis patients with an inadequate response to on-label use of dupilumab. World Allergy Organ J. 2024 July;17(7):100923.
18. Ludwig CM, Krase JM, Price KN, Lio PA, Shi VY. A practical guide for transitioning from classical immunosuppressants to dupilumab in atopic dermatitis. J Dermatol Treat. 2021 July 4;32(5):503–6
Baseline characteristics of atopic eczema patients enrolled in seven European registries united in the TREatment of ATopic eczema (TREAT) registry taskforce
No full text\ua9 2025 The Author(s). 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: The TREAT Registry Taskforce is a collaborative effort of international registries aiming to provide real-world data on the long-term efficacy, cost-effectiveness and safety of systemic treatments and phototherapy for atopic eczema (AE). Objectives: This study seeks to present a comprehensive overview of the demographics, prior systemic treatments, clinical characteristics and disease severity and burden at baseline among patients enrolled in seven TREAT registries. Moreover, the aim is to gain insight into the differences between the registries and to explore the current prescribing practices of various therapies for patients with AE across Europe. Methods: Data from June 2016 to 31 October 2022, were collected from seven observational cohorts: A-STAR (UK/Ireland), AtopyReg (Italy), Biobadatop (Spain), SCRATCH (Denmark), SwedAD (Sweden), TREATgermany (Germany) and TREAT NL/BE (Netherlands/Belgium). Results: The analysis included 5337 patients, with a mean age of 39.1 years (6.3% paediatric, 54.4% male). Of these, 84.1% had previously received systemic treatments, primarily systemic corticosteroids (58.8%) and ciclosporin (39.0%), while 30.1% had undergone phototherapy. At enrolment, dupilumab was the most prescribed treatment (75.0%), followed by ciclosporin (7.8%) and Janus Kinase inhibitors (5.9%); only 1.7% started phototherapy. Baseline assessments showed that most patients had moderate (41.9%) to severe (30.1%) AE, with an average Eczema Area and Severity Index (EASI) score of 17.6. The Patient-Oriented Eczema Measure (POEM) score averaged 17.2, indicating severe disease impact. The Dermatology Life Quality Index (DLQI) score averaged 13.4, and the Numerical Rating Scale (NRS) for itch was 6.4. Conclusions: This pooled analysis from the TREAT Registry Taskforce highlights the variability and similarities in data collection across national registries, providing significant insights into the baseline characteristics of the patient population. It establishes a robust foundation for future analyses of key effectiveness and safety outcomes
