Sustained patient use and improved outcomes with digital transformation of a COPD service: RECEIVER trial and DYNAMIC-SCOT COVID-19 scale-up response.

IntroductionLenusCOPD has been co-designed to enable digital transformation of COPD services for proactive preventative care. Patient-facing progressive web application, clinician dashboard and support website integrate patient-reported outcomes (PROs), self-management resources, structured clinical summary, wearable and home NIV data with asynchronous patient-clinician messaging. We commenced the implementation-effectiveness observational cohort RECEIVER trial in September 2019, with the primary endpoint of sustained patient usage and secondary endpoints including admissions, mortality, exacerbations, service workload and quality of life. We paused recruitment in March 2021 and provided LenusCOPD as routine care in the "DYNAMIC-SCOT" COVID-19 response service scale-up. Methods83 RECEIVER trial participants and 142 DYNAMIC-SCOT participants had completed minimum 1 year follow-up when we censored data on 31st August 2021. We established a control cohort with 5 patients matched per RECEIVER participant from de-identified contemporary routine clinical data. ResultsSustained patient app utilisation was noted in both cohorts. Median time to admission or death was 43 days in control, 338 days in RECEIVER and 400 days in DYNAMIC-SCOT participants who had had a respiratory-related admission in the preceding year. The 12-month risk of admission or death was 74% in control patients, 53% in RECEIVER and 47% in the DYNAMIC-SCOT sub-cohort participants. There was a median of 2.5 COPD exacerbations per patient per year with stable quality of life across follow up and a manageable workload for clinical users. ConclusionsA high proportion of people continued to use the co-designed LenusCOPD application during extended follow-up. Outcome data supports scale-up of this digital service transformation. Key messages What is the key question?Can sustained patient interaction and improved patient outcomes be achieved with digital transformation of a COPD service? What is the bottom line?Participants continue to use the LenusCOPD patient app, with an average of 3-3.5 interactions per person per week sustained >1-year post-onboarding. COPD- related hospital admissions and occupied bed days were reduced following LenusCOPD onboarding in participants with a history of a severe exacerbation in the previous year, with a median time to readmission of 380 days compared with 50 days in a contemporary matched control patient cohort. Why read on?Feasibility and utility results support scale-up adoption of these digital tools, to support optimised co-management of COPD and other long-term conditions within a continuous implementation-evaluation framework. This will establish a test-bed infrastructure for additional innovations including artificial intelligence-insights for MDT decision support.

The protein kinase LKB1 promotes self-renewal and blocks invasiveness in glioblastoma.

The role of liver kinase B1 (LKB1) in glioblastoma (GBM) development remains poorly understood. LKB1 may regulate GBM cell metabolism and has been suggested to promote glioma invasiveness. After analyzing LKB1 expression in GBM patient mRNA databases and in tumor tissue via multiparametric immunohistochemistry, we observed that LKB1 was localized and enriched in GBM tumor cells that co-expressed SOX2 and NESTIN stemness markers. Thus, LKB1-specific immunohistochemistry can potentially reveal subpopulations of stem-like cells, advancing GBM patient molecular pathology. We further analyzed the functions of LKB1 in patient-derived GBM cultures under defined serum-free conditions. Silencing of endogenous LKB1 impaired 3D-gliomasphere frequency and promoted GBM cell invasion in vitro and in the zebrafish collagenous tail after extravasation of circulating GBM cells. Moreover, loss of LKB1 function revealed mitochondrial dysfunction resulting in decreased ATP levels. Treatment with the clinically used drug metformin impaired 3D-gliomasphere formation and enhanced cytotoxicity induced by temozolomide, the primary chemotherapeutic drug against GBM. The IC50 of temozolomide in the GBM cultures was significantly decreased in the presence of metformin. This combinatorial effect was further enhanced after LKB1 silencing, which at least partially, was due to increased apoptosis. The expression of genes involved in the maintenance of tumor stemness, such as growth factors and their receptors, including members of the platelet-derived growth factor (PDGF) family, was suppressed after LKB1 silencing. The defect in gliomasphere growth caused by LKB1 silencing was bypassed after supplementing the cells with exogenous PFDGF-BB. Our data support the parallel roles of LKB1 in maintaining mitochondrial homeostasis, 3D-gliomasphere survival, and hindering migration in GBM. Thus, the natural loss of, or pharmacological interference with LKB1 function, may be associated with benefits in patient survival but could result in tumor spread.

Implementation of novel and conventional outbreak control measures in managing a COVID-19 outbreak in a large UK prison

BackgroundSARS-CoV-2 can spread rapidly within correctional facilities. On, following identification of a confirmed COVID-19 case in a prisoner in Prison A (UK), an Outbreak Control Team was convened consisting of prison staff and public health experts from Public Health England and the UK National Health Service. MethodsAt the start of the outbreak, four prisoners and 40 staff were isolating with COVID-19 symptoms. An outbreak was declared and full prison lockdown implemented. Prompt implementation of novel outbreak control measures prevented an explosive prison outbreak, specifically establishment of dedicated isolation and cohorting units, including (i) Reverse Cohorting Units (RCUs) for accommodating new detainees; (ii) Protective Isolation Units (PIUs) for isolating symptomatic prisoners (new detainees and existing residents), and (iii) Shielding Units (SUs) to protect medically vulnerable prisoners. FindingsIn total, 120 probable and 25 confirmed cases among prisoners and staff were recorded between. Among prisoners, there were six possible, 79 probable, and three confirmed cases. Among staff, there were 83 possible, 79 probable, and 22 confirmed cases. Testing of symptomatic prisoners was limited for most of the outbreak, with only 33% of probable cases tested. This explains the low number of confirmed cases (three) among prisoners despite the large number of probable cases (n=81; 92%). Over 50% of the initial cases among prisoners were on the two wings associated with the index case. InterpretationRapid transmission of SARS-COV-2 was prevented through proactive steps in identifying and isolating infected prisoners (and staff), cohorting new admissions and shielding vulnerable individuals. These novel and cost-effective approaches can be implemented in a wide range of correctional facilities globally and proved effective even in the absence of mass testing. Funding Sourcenone Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA systematic literature search on Pubmed from database inception to October 2020 was conducted. The broad terms included were "COVID-19" OR "SARS-COV-2" OR "coronavirus" AND "prison" OR "correctional facility" OR "place of detention" OR "penitentiary" OR "detention centre". There were no language restrictions. We reviewed reference lists and forward citations of all articles pertinent to the study objectives. We identified 122 results. Only two prison outbreak reports were identified, both focusing on prisons in the USA. Outbreak guidance identified during the literature review was typically adapted from other institutional settings such as care homes and hospital, with a focus on self-isolation, social distancing, reduced admissions and rapid testing. Many of these features form the basis of CDC, WHO and ECDC prison outbreak guidance. However, these measures have not proven effective in many countries, resulting in major and sustained COVID-19 outbreaks in regions such as the USA and South America. Therefore, alternative and cost-effective approaches need to be considered to reduce the transmission of SARS-COV-2. Added value of this studyThis study outlines novel outbreak control measures (not reported elsewhere in the literature), that were clearly efficacious in preventing the rapid transmission of SARS-COV-2 in a large UK prison. These include: (1) the timely establishment of "Reverse Cohorting Units" to accommodate new prison admissions, allowing emergent infectious cases to be detected before entering the general population; (2) "Protective Isolation Units" for accommodating confirmed / suspected cases and (3) "Shielding Units" to protect prisoners most at risk from COVID-19. Implications of all the available evidenceThe innovative and cost-effective interventions presented here proved effective in controlling the spread of SARS-COV-2, even in the absence of mass testing. The best defence against incursions of future infection into global prisons is implementation of strict outbreak control measures, specifically the screening and quarantining of new prison admissions.