Algorithmic approach to finding people with multiple sclerosis using routine healthcare data in Wales.

BACKGROUND: Identification of multiple sclerosis (MS) cases in routine healthcare data repositories remains challenging. MS can have a protracted diagnostic process and is rarely identified as a primary reason for admission to the hospital. Difficulties in identification are compounded in systems that do not include insurance or payer information concerning drug treatments or non-notifiable disease. AIM: To develop an algorithm to reliably identify MS cases within a national health data bank. METHOD: Retrospective analysis of the Secure Anonymised Information Linkage (SAIL) databank was used to identify MS cases using a novel algorithm. Sensitivity and specificity were tested using two existing independent MS datasets, one clinically validated and population-based and a second from a self-registered MS national registry. RESULTS: From 4 757 428 records, the algorithm identified 6194 living cases of MS within Wales on 31 December 2020 (prevalence 221.65 (95% CI 216.17 to 227.24) per 100 000). Case-finding sensitivity and specificity were 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% for the self-declared registry population. DISCUSSION: The algorithm successfully identified MS cases within the SAIL databank with high sensitivity and specificity, verified by two independent populations and has important utility in large-scale epidemiological studies of MS.

Contemporary study of multiple sclerosis disability in South East Wales.

BACKGROUND: A contemporary understanding of disability evolution in multiple sclerosis (MS) is an essential tool for individual disease management and planning of interventional studies. We have used prospectively collected longitudinal data to analyse disability progression and variation in a British MS cohort. METHODS: Cox proportional hazards regression was used to estimate hazard of Expanded Disability Status Scale (EDSS) 4.0 and 6.0. A continuous Markov model was used to estimate transitional probabilities for individual EDSS scores. Models were adjusted for age at MS onset, sex and disease-modifying treatments (DMTs) exposure. RESULTS: 2135 patients were included (1487 (70%) female, 1922 (89%) relapsing onset). 865 (41%) had used DMTs. Median time to EDSS 4.0 and 6.0 was 18.2 years (95% CI 16.3 to 20.2) and 22.1 years (95% CI 20.5 to 24.5). In the Markov model, the median time spent at EDSS scores of <6 (0.40-0.98 year) was shorter than the time spent at EDSS scores of ≥6 (0.87-4.11 year). Hazard of change in EDSS was greatest at EDSS scores <6 (HR for increasing EDSS: 1.02-1.33; decreasing EDSS: 0.34-1.27) compared with EDSS scores ≥6 (HR for increasing EDSS: 0.08-0.61; decreasing EDSS: 0.18-0.54). CONCLUSIONS: These data provide a detailed contemporary model of disability outcomes in a representative population-based MS cohort. They support a trend of increasing time to disability milestones compared with historical reference populations, and document disability variation with the use of transitional matrices. In addition, they provide essential information for patient counselling, clinical trial design, service planning and offer a comparative baseline for assessment of therapeutic interventions.

Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached.

Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cancer cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. Excess FAs are toxic to non-transformed cells but surprisingly not to cancer cells. Molecules underlying this cancer adaptation may provide alternative drug targets. Here, we demonstrate that diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, is frequently up-regulated in melanoma, allowing melanoma cells to tolerate excess FA. DGAT1 over-expression alone transforms p53-mutant zebrafish melanocytes and co-operates with oncogenic BRAF or NRAS for more rapid melanoma formation. Antagonism of DGAT1 induces oxidative stress in melanoma cells, which adapt by up-regulating cellular reactive oxygen species defenses. We show that inhibiting both DGAT1 and superoxide dismutase 1 profoundly suppress tumor growth through eliciting intolerable oxidative stress.

Virtual Health Care for Community Management of Patients With COVID-19 in Australia: Observational Cohort Study.

BACKGROUND: Australia has successfully controlled the COVID-19 pandemic. Similar to other high-income countries, Australia has extensively used telehealth services. Virtual health care, including telemedicine in combination with remote patient monitoring, has been implemented in certain settings as part of new models of care that are aimed at managing patients with COVID-19 outside the hospital setting. OBJECTIVE: This study aimed to describe the implementation of and early experience with virtual health care for community management of patients with COVID-19. METHODS: This observational cohort study was conducted with patients with COVID-19 who availed of a large Australian metropolitan health service with an established virtual health care program capable of monitoring patients remotely. We included patients with COVID-19 who received the health service, could self-isolate safely, did not require immediate admission to an in-patient setting, had no major active comorbid illness, and could be managed at home or at other suitable sites. Skin temperature, pulse rate, and blood oxygen saturation were remotely monitored. The primary outcome measures were care escalation rates, including emergency department presentation, and hospital admission. RESULTS: During March 11-29, 2020, a total of 162 of 173 (93.6%) patients with COVID-19 (median age 38 years, range 11-79 years), who were diagnosed locally, were enrolled in the virtual health care program. For 62 of 162 (38.3%) patients discharged during this period, the median length of stay was 8 (range 1-17) days. The peak of 100 prevalent patients equated to approximately 25 patients per registered nurse per shift. Patients were contacted a median of 16 (range 1-30) times during this period. Video consultations (n=1902, 66.3%) comprised most of the patient contacts, and 132 (81.5%) patients were monitored remotely. Care escalation rates were low, with an ambulance attendance rate of 3% (n=5), emergency department attendance rate of 2.5% (n=4), and hospital admission rate of 1.9% (n=3). No deaths were recorded. CONCLUSIONS: Community-based virtual health care is safe for managing most patients with COVID-19 and can be rapidly implemented in an urban Australian setting for pandemic management. Health services implementing virtual health care should anticipate challenges associated with rapid technology deployments and provide adequate support to resolve them, including strategies to support the use of health information technologies among consumers.

Shrub establishment favoured and grass dominance reduced in acid heath grassland systems cleared of invasive Rhododendron ponticum.

Rhododendron ponticum L. is a damaging invasive alien species in Britain, favouring the moist, temperate climate, and the acidic soils of upland areas. It outshades other species and is thought to create a soil environment of low pH that may be higher in phytotoxic phenolic compounds. We investigated native vegetation restoration and R. ponticum regeneration post-clearance using heathland sites within Snowdonia National Park, Wales; one site had existing R. ponticum stands and three were restoring post-clearance. Each site also had an adjacent, uninvaded control for comparison. We assessed whether native vegetation restoration was influenced post-invasion by soil chemical properties, including pH and phytotoxic compounds, using Lactuca sativa L. (lettuce) bioassays supported by liquid chromatography-mass spectroscopy (LC-MSn). Cleared sites had higher shrub and bare ground cover, and lower grass and herbaceous species cover relative to adjacent uninvaded control sites; regenerating R. ponticum was also observed on all cleared sites. No phenolic compounds associated with R. ponticum were identified in any soil water leachates, and soil leachates from cleared sites had no inhibitory effect in L. sativa germination assays. We therefore conclude that reportedly phytotoxic compounds do not influence restoration post R. ponticum clearance. Soil pH however was lower beneath R. ponticum and on cleared sites, relative to adjacent uninvaded sites. The lower soil pH post-clearance may have favoured shrub species, which are typically tolerant of acidic soils. The higher shrub cover on cleared sites may have greater ecological value than unaffected grass dominated sites, particularly given the recent decline in such valuable heathland habitats. The presence of regenerating R. ponticum on all cleared sites however highlights the critical importance of monitoring and re-treating sites post initial clearance.