The Effect of Remote Digital Services on Health Care Inequalities Among People Under Long-Term Dermatology Follow-Up: Cross-Sectional Questionnaire Study.

BACKGROUND: Given the expansion of remote digital dermatology services from the National Health Service, particularly during the COVID-19 pandemic, there is a need for methods that identify patients at risk of digital exclusion to guide equitable representation in service co-design processes and tailor remote services to the needs of their patient population. OBJECTIVE: This quality improvement project aims to inform the redesign of remote services to optimally support the ongoing needs of patients with chronic skin diseases, ensuring that the services are tailored to patients' digital health literacy requirements. METHODS: We profiled the digital health literacy of 123 people with chronic skin conditions who require long-term surveillance in 2 specialist clinics (London, United Kingdom) using the Multidimensional Readiness and Enablement Index for Health Technology (READHY) questionnaire alongside the Optimizing Health Literacy and Access (Ophelia) process for hierarchical cluster analysis. RESULTS: The cluster analysis of READHY dimensions in responding participants (n=116) revealed 7 groups with distinct digital and health literacy characteristics. High READHY scores in groups 1 (n=22, 19%) and 2 (n=20, 17.2%) represent those who are confident with managing their health and using technology, whereas the lower-scoring groups, 6 (n=4, 3.4%) and 7 (n=12, 10.3%), depended on traditional services. Groups 3 (n=27, 23.3%), 4 (n=23, 19.8%), and 5 (n=8, 6.9%) had varying digital skills, access, and engagement, highlighting a population that may benefit from a co-designed dermatology service. CONCLUSIONS: By identifying patient groups with distinguishable patterns of digital access and health literacy, our method demonstrates that 63.8% (n=74) of people attending specialist clinics in our center require support in order to optimize remote follow-up or need an alternative approach. Future efforts should streamline the READHY question profile to improve its practicality and use focus groups to elicit strategies for engaging patients with digital services.

Topical treatment of actinic keratoses in organ transplant recipients: a feasibility study for SPOT (Squamous cell carcinoma Prevention in Organ transplant recipients using Topical treatments).

BACKGROUND: The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5-fluorouracil (5-FU) may be chemoprotective in immunocompetent patients. OBJECTIVES: To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs. METHODS: OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5-FU, 5% imiquimod (IMIQ) or sunscreen (sun-protective factor 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re-treated. AK activity [AK clearance, new AK development, patient-centred outcomes (toxicity, health-related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed. RESULTS: Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re-treated). AK activity analyses found 5-FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5-FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5-FU, HRQoL outcomes were similar. CONCLUSIONS: Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5-FU-based treatments in future phase III trials. What is already known about this topic? Cutaneous squamous cell carcinoma (cSCC) is significantly more common in immunocompromised individuals including organ transplant recipients (OTRs) compared with immunocompetent populations. cSCC chemoprevention activity of sunscreen and 5-fluorouracil-based (5-FU) actinic keratosis (AK) treatments has been demonstrated in randomized controlled trials (RCTs) in immunocompetent populations but not in OTRs. AKs are cSCC precursors and their clearance and prevention are generally regarded as surrogate endpoint biomarkers for potential cSCC chemoprevention activity. What does this study add? SPOT (SCC Prevention in OTRs using Topical treatments) has confirmed that RCTs of OTR-cSCC chemoprevention with topical AK treatments are feasible. It also suggests that topical 5-FU may be superior to 5% imiquimod and sunscreen in AK clearance and prevention. Together with recent evidence from several RCTs in the general population, these data provide a compelling rationale for further studies of intervention with 5-FU-based topical chemoprevention approaches in OTR-cSCC prevention.

Deletion of SenX3-RegX3, a key two-component regulatory system of Mycobacterium smegmatis, results in growth defects under phosphate-limiting conditions.

Two component regulatory systems are key elements in the control of bacterial gene expression in response to environmental perturbations. The SenX3-RegX3 system is implicated in the control of phosphate uptake in Mycobacterium smegmatis and Mycobacterium tuberculosis. regX3 is reported to be essential in M. smegmatis, but not in M. tuberculosis. We attempted to construct complete senX3-regX3 operon deletion strains of M. smegmatis; initially we found that the operon could only be deleted when another functional copy was provided. Using a strain in which the only functional copy of the operon was present on an integrating plasmid, we attempted to replace the functional copy with an empty vector. Surprisingly, we obtained strains in which the functional copy had been deleted from the chromosome at a low frequency. We deleted the senX3 gene in a similar fashion, but it was not possible to delete regX3 alone. To identify possible compensatory mutations we sequenced the whole genome of two deletion strains and the wild-type. A synonymous single nucleotide polymorphism (SNP) in a lipoprotein was found in all deletion strains, but not the parental strains, and a frameshift mutation in nhaA was identified in three of the four deletion strains. Operon deletion strains were more sensitive to phosphate limitation, showing a reduced ability to grow at lower phosphate concentrations. The M. tuberculosis operon was able to functionally complement the growth phenotype in M. smegmatis under phosphate-replete conditions, but not under low phosphate conditions, reinforcing the difference between the two species. Our data show that, in contrast with previous reports, it is possible to delete the operon in M. smegmatis, possibly due to the accumulation of compensatory mutations, and that the deletion does affect growth in phosphate.