Harrogate and District NHS Foundation Trust

Dengue is a climate-sensitive infectious disease and the world's fastest-growing vector-borne disease. It disproportionately affects low- and middle-income countries (LMICs), with children most severely affected. Dengvaxia (CYD-TDV) and Qdenga (TAK-003) are the only two licensed dengue vaccines currently available, while Butantan-DV (TV003) is an advanced candidate with promising Phase 3 clinical trial results. Despite the commercial availability of dengue vaccines, coverage remains low in areas with the greatest need. This is driven by technical, social, and geopolitical challenges, as well as growing vaccine hesitancy. There is also an added layer of clinical complexity associated with vaccination against dengue due to the antibody-dependent enhancement (ADE) phenomenon, which can lead to vaccine-enhanced disease. Here, we review the current global landscape of dengue vaccine licensure and coverage, focusing on countries with the highest disease burden. We show that in many countries with a high dengue incidence, dengue vaccines have yet to be licensed, particularly in parts of Africa and South Asia. Even in regions where licensure is more widespread, such as Latin America and Southeast Asia, dengue vaccines are not well integrated into national immunisation programmes and can only be obtained through out-of-pocket payment. We therefore identify several state and market-driven systemic factors, as well as declining vaccine confidence, as barriers to scaling up dengue vaccine access in LMICs. These barriers must be addressed through creative solutions to ensure the equitable distribution of dengue vaccines to the populations and countries that need them the most.

A 50-year-old man with a background of idiopathic CD4+ lymphocytopenia (ICL) was successfully treated with acitretin monotherapy for recalcitrant viral warts on the hands and right cheek. Treatment duration was 35 months, with sustained effects at 15 months post-acitretin therapy. Side-effects were mild and included mild cheilitis and dryness of nasal mucosa. CD4+ lymphocytes play an important role in enabling host responses to human papillomavirus (HPV) and, consequently, lower CD4 counts correspond to a higher risk of chronic HPV infection, including viral warts. HPV represents the most common opportunistic infection in patients with ICL. Acitretin is an oral retinoid with affinity for retinoic acid and retinoid X receptors, and works through downregulation of signal transducer and activator of transcription (STAT)1- and STAT3-dependent signalling, with resultant increases in keratinocyte differentiation. As HPV evades the Janus kinase/STAT pathway to promote keratinocyte proliferation, acitretin may work through reversal of this mechanism. This case demonstrates effectiveness of acitretin in treating recalcitrant viral warts, specifically in a patient with ICL.

The foot and ankle are frequently affected in rheumatic and musculoskeletal diseases (RMDs), yet there is a lack of high-quality evidence to determine the effectiveness of treatments. Outcomes in research are often inconsistently measured, impeding evidence synthesis. Additionally, clinical decisions are based on research outcomes, but these are not always regarded as important by people with RMDs. This study aimed to determine domains of importance to people with RMDs who have experienced foot and ankle disorders, and aid in developing a standardised core outcome set (COS) to address these issues. Participants from four continents (Europe, Africa, Australia, North America) were recruited to semi-structured interviews through clinical departments and electronic mailing lists. Analysis was conducted using a mixed deductive/inductive approach to the framework method. Patient research partners co-produced the interview schedule and recruitment materials, and co-interpreted results. Fifty-six participants (age range 27 to 76 years; 66 % female), with foot and ankle disorders in a variety of RMDs (including inflammatory arthritis, osteoarthritis, crystal arthropathies, connective tissue diseases), were interviewed. Sixteen domains were described by participants: pain, physical function, fatigue, deformity, skin and nail health, swelling, temperature, numbness, poor circulation, cramping, activities/participation, footwear impact, psychological impact, sleep, healthcare utilisation and personal expenses. Most domains were considered important to participants regardless of RMD or geographic location. Foot and ankle disorders have far-reaching consequences for people with RMDs. This large qualitative study provides a foundation for achieving international consensus on a core outcome set for foot and ankle disorders in RMDs, to improve the quality of evidence demonstrating effectiveness of treatments.

BackgroundThe integration of artificial intelligence (AI) in radiology has the potential to improve diagnostic accuracy and efficiency. Medical students and junior doctors will likely use AI more frequently in the future, making their perceptions essential for identifying educational gaps.PurposeTo explore the perceptions of UK medical students and junior doctors regarding AI in radiology.Material and MethodsA cross-sectional survey was distributed across UK medical schools and foundation programs. A total of 250 responses were analyzed using descriptive statistics and non-parametric tests, focusing on career impact, clinical effectiveness, educational development, and ethical concerns.ResultsMost respondents (55.2%) were undeterred by career uncertainties related to AI, with 64% confident that AI would not replace radiologists. Up to 80.6% supported AI's clinical benefits, and 63.2% endorsed its educational integration. However, there were concerns about job displacement and insufficient AI training. Medical students were more worried about job security than junior doctors, while those committed to radiology were less apprehensive and viewed AI as complementary.ConclusionEducational programs and regulatory frameworks are essential to facilitate AI integration in radiology. Addressing concerns about job displacement and improving AI education will be key to preparing future radiologists for technological advancements.

Metastatic basal cell carcinomas (mBCCs) are exceedingly rare, with an estimated variable prevalence rate between 0.003 and 0.55% among all basal cell carcinomas. Although there are hundreds of reported cases of mBCCs, a dearth of evidence exists of mBCCs in patients with Gorlin syndrome-an autosomal dominant genetic disorder. The purpose of this article was to present the first and largest case series of patients with mBCC in Gorlin. A literature review (LR) compares our data with the existing evidence base to underscore the importance of early surveillance, diagnosis and surgical intervention of suspicious lesions as distant metastases significantly reduce survival rates.

The practice of dentistry contributes to 3% of the carbon footprint of the NHS. As awareness and concern about climate change increases, all dental care professionals must play their part in reducing the environmental impact of the care they provide. This paper aims to describe a novel method of teaching, both the theory and practical application of sustainable dentistry, by integrating sustainable quality improvement methods into the existing management and leadership requirements of dental core training.

Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5 + -DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus. This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018-December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5 + -DM outbreak. Sixty new anti-MDA5+, but not other MSAs surged between 2020-2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. Few (8/60) had a prior history of COVID-19, whereas 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Abstract Background The use of decentralised clinical trials (which bring trials to patients through remote processes and technology versus central on-site visits) has been thought to be a potential solution to common recruitment and retention barriers. However, there is a lack of evidence to understand the experiences, needs and preferences of the public to inform trial methodologies that appeal to different populations. We report participant experiences of SAFA, a partially decentralised randomised clinical trial, to inform the methodology used in future dermatology trials that aim to appeal to women aged 18 and over. Methods Participants of the SAFA (Spironolactone for Adult Female Acne) trial were invited to take part in a qualitative semi-structured interview to explore their experience and perspectives of taking part in the trial. Questions focused on their experience of using decentralised methods to access and enrol in the trial (e.g. social media advertising), in addition to the decentralised trial visit and data collection methods used throughout. Interviews were conducted remotely, recorded, and transcribed. Data were analysed using reflexive Thematic Analysis. Results Twelve SAFA participants (all women, age range 22-36) were interviewed. Initially, participants were influenced to enrol by trusted online information, the feeling of validation the trial provided and the convenience and flexibility offered by the decentralised methods and research staff made participants feel valued and enabled them to engage in the trial with minimal interference to existing commitments. SAFA participants were generally accepting of trial demands, such as the text-heavy paperwork and on-site visits for blood collection and highlighted several areas relevant for trial conduct going forwards including where decentralised methods may (and may not) be accepted and how trial accessibility and understanding could be improved. Conclusions The study has shown that decentralised methods used by responsive and approachable staff were widely accepted in the SAFA trial. Interviewees found the methods adopted in the SAFA trial helped the trial to fit with their needs and promoted a sense of feeling valued that encouraged ongoing trial engagement. Decentralised methods should be considered favourably when designing a dermatology trial as they can potentially enhance both recruitment and retention. Trial registration number: ISRCTN number: 12892056