Agne Ulyte

Background: Chronic obstructive pulmonary disease affects around 2% United Kingdom population. Timely identification of patients at risk of deterioration is crucial. Technology-enabled remote monitoring may help prevent deterioration, support chronic obstructive pulmonary disease patients at home and appropriate use of National Health Service services. Evidence on the adoption, use and experience of technology-enabled remote monitoring in the chronic obstructive pulmonary disease pathway is currently limited, impeding efforts to inform effective technology-enabled remote monitoring design and implementation. Objective: To understand what supports good practice in the implementation and use of technology-enabled remote monitoring in the chronic obstructive pulmonary disease care pathway and draw transferable lessons that can inform spread and scale up. Design and methods: Rapid evaluation, combining qualitative interviews, focused case studies and stakeholder workshops. Patient and public voices informed evaluation design, conduct and co-design of resources. Setting and participants: Scoping interviews with a purposive sample of 29 national and regional stakeholders informed selection of four case study sites involved in delivering technology-enabled remote monitoring for chronic obstructive pulmonary disease. Case studies combined interviews with 19 staff and review of 18 documents. Analysis was informed by the non-adoption, abandonment and challenges to scale-up, spread and sustainability of technology framework. A stakeholder workshop ( n = 23 participants) refined emerging findings. Interviews with respiratory patients and a co-design workshop informed development of patient-facing resources. Results: Technology-enabled remote monitoring for chronic obstructive pulmonary disease occurs along a continuum of scope and scale. Technology-enabled care pathways have some common overarching features, but variation is seen across contexts and patient cohorts. Technology-enabled remote monitoring services influence care provision on a system level. Effective implementation is underpinned by service characteristics affecting its use, technology functionalities and organisational capabilities and capacities. Technology-enabled remote monitoring success also depends on defining the data-driven purpose and value proposition, ensuring buy-in, organising the workforce and workload in sustainable ways, data and IT platform interoperability, support for patients in using the service safely and appropriately, utilising existing resources, team buy-in, financial resourcing and clear policy incentives, and openness to ongoing learning. Patients value technology-enabled remote monitoring services that help them feel more connected to healthcare providers and provide timely information and support. Healthcare staff value high-quality patient care, services value affordability and sustainable workload impact. Limitations: Small-scale qualitative evaluation conducted at pace. Conclusions: Technology can support remote monitoring but is only one aspect of an effective technology-enabled remote monitoring service. It needs to be embedded in the chronic obstructive pulmonary disease pathway and align with service needs and existing capacity in cost-effective ways and with proportionate oversight of quality and safety. Decision-makers need to consider which aspects of the technology are essential, how they can be effectively embedded and supported by an appropriately equipped workforce, and needs of different patient cohorts. Future work: There is a need for evidence on longer-term effectiveness and cost-effectiveness of technology-enabled remote monitoring for chronic obstructive pulmonary disease, impact on patient and staff experience, and issues of equity of access. Qualitative and quantitative approaches are needed to appreciate varied technology and evolving use in different settings/groups. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR154231.

STUDY AIMS: The prevalence of Long COVID in children and adolescents is heterogeneous, ranging from 1% to 51%, depending on the population studied. The lack of a standardised approach for establishing a Long COVID diagnosis in children and adolescents complicates the accurate assessment of prevalence, risk factors and outcomes. The present study aimed to examine the value of standardised interviews and an adjudication process to better understand self- or proxy-reported symptoms lasting longer than 12 weeks compatible with Long COVID in children and adolescents during the COVID-19 pandemic. METHODS:We conducted a school-based, prospective cohort study (Ciao Corona) from March 2020 to July 2022 in the Canton of Zurich, Switzerland. Of 156 invited schools, 55 agreed to participate. Primary schools were randomly selected across all 12 districts of the Canton of Zurich, with nearby secondary schools subsequently invited. Within participating schools, classes were randomly selected, stratified by school level, and all students aged 6–17 years in selected classes were eligible. At three different time points (March/April 2021, November/December 2021 and June/July 2022), school-aged children and adolescents underwent serology testing and completed online questionnaires, including questions on symptoms lasting ≥12 weeks compatible with Long COVID. We invited those with persisting symptoms and who were seropositive for SARS-CoV-2 – whether “infected” i.e. infection and no vaccination or having “hybrid immunity” i.e. infection and vaccination – to participate in interviews to allow us to better understand the pattern, severity and timing of the reported symptoms. An adjudication process with experts then followed to assess the probability of Long COVID. RESULTS: 39/1120 (3.5%) seropositive children and adolescents (i.e. infected or with hybrid immunity) reported persisting symptoms (≥12 weeks). The most frequently reported symptoms were headache, tiredness and stomach ache. In 20/39 (51%) with persisting symptoms who agreed to be interviewed, the adjudication committee concluded that Long COVID was unlikely in 13 (65%), possible in 7 (35%) and likely in 0 participants. CONCLUSIONS: Relying exclusively on self- or proxy-reported questionnaire data, without more detailed information may overestimate Long COVID in children and adolescents. Implementing standardised interviews and an adjudication process helps to contextualise self- or proxy-reported symptoms compatible with Long COVID. Trial registration: https://clinicaltrials.gov NCT04448717.

Background There is considerable interest in technology-enabled remote monitoring in the UK. The aim is to respond to system pressures and improve access, experience and quality of care. There is an urgent need for process, outcome and impact evaluations of interventions at various stages of development and implementation to address evidence gaps around adoption, spread, sustainability and inequalities. Aim DECIDE (Digitally Enabled Care in Diverse Environments) is a centre for rapid evaluation of technology-enabled remote monitoring funded by the National Institute for Health and Care Research (2023 to 2026). It aims to support service users, service commissioners and providers of remote monitoring services, to enable high quality care. Example questions include: Is the technology-enabled remote monitoring innovation needed and, if so, for whom? How are technology-enabled care pathways implemented, and what are associated outcomes and impacts? What are the opportunities and challenges for sustainability, scale-up and spread? Methods A range of qualitative, quantitative and economic methods will be used. Exact methods and questions will be dependent on the focus, scope and scale of each evaluation. Evaluations will be informed by relevant theory, including the Non-Adoption, Abandonment and the challenges to Spread, Scale-up and Sustainability of technological innovation in health and care (NASSS) framework. A User Advisory Group and External Steering Committee, both with diverse voices, will help shape evaluation design, implementation and dissemination. Project-led dissemination will ensure timely sharing of insights and support impact. Conclusion Evaluations will advance understanding of when and for whom technology-enabled remote monitoring innovation is needed; how it works and how factors related to the intervention, implementation process and wider context influence adoption; associated outcomes and impacts, whether and how these tackle inequalities; and potential challenges to scale and spread. We aim to inform decision-making by policymakers, commissioners, providers, patients/service users and researchers.

Objective: To examine whether regions participating in the NHS-Galleri trial of a cell-free DNA-based multi-cancer early detection (MCED) test experienced changes in cancer diagnostic delay rates that could indicate the presence of spillover due to constraints on care delivery. Design: Quasi-experimental difference-in-differences analysis. Setting: England, April 2021-September 2024. Participants: All 21 cancer alliance regions in England, 8 of which participated in the trial. Main outcomes: Cancer diagnostic delay rates (primary outcome) and referral rates (secondary outcome). Primary analysis focused on the group of three cancer types (head and neck, lung, upper gastrointestinal) that are prespecified in the trial protocol, have higher signal detection for cell-free DNA-based testing, and were not subject to routine screening. A difference-in-differences analysis was used to compare outcomes in regions participating in NHS-Galleri to regions that did not participate, before and after the start of the trial. Results: Diagnostic delay rates increased in the first six months of the trial for the primary group of three cancer types in participating regions compared to non-participating regions (adjusted difference-in-differences 3.4 percentage points, 95% CI: 1.9-5.0, p<0.001). These differences persisted from 6 to 12 months after trial start and receded over the following two years. No significant change in referral rates for this group of cancer types was observed. Conclusions: Participation in the NHS-Galleri trial was associated with increased diagnostic delay rates for the primary group of high-detection cancer types. The trial may have led to higher demand for limited diagnostic resources (e.g. imaging, endoscopy) required for follow-up of suspected cancer arising from positive MCED test results or usual care processes. If patients in the control group faced delayed diagnosis as a result, this would represent spillover during the first year of the trial and could lead to overestimation of MCED benefit. Summary Box: What is already known on this topic: The NHS-Galleri trial randomized over 140,000 adults to receive usual cancer screening or usual screening plus a new cell-free DNA-based multi-cancer early detection test in 8 out of 21 regions in England. During the trial, higher use of scarce cancer diagnostic services by the intervention group could have led to reduced availability of services for members of the control group and patients not enrolled in the trial. The potential for this form of spillover to bias trial results and affect patient access to care is not addressed in the medical literature, guidance on clinical trial methods, or the NHS-Galleri trial protocol. What this study adds: In the first year of the trial, participating regions experienced a modest increase in region-wide diagnostic delay rates for cancer types having higher signal detection for cell-free DNA-based testing. Increased diagnostic delays could contribute to stage shift for some control group patients and lead to overestimation of the Galleri test’s effect on early detection of cancer. Future trials of multi-cancer early detection tests and other interventions that affect utilization of limited healthcare resources should address the potential for spillover due to constraints on care delivery to affect patient outcomes and trial results.

Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological, and social factors in a large longitudinal population-based sample. Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort study Ciao Corona in Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc.), psychological (sadness, anxiousness, stress), and social (nationality, parents’ education, etc.) factors, were assessed in 2020 and 2021 and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level. Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness, and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions, or nationality, were determinants only in individual subscales.Conclusion: Recent mental health, more than biological, physical, or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group. What is Known:• Assessing health-related quality of life (HRQOL) in children and adolescents aids in understanding how life circumstances impact their well-being.• HRQOL is a complex construct, involving biological, psychological, and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples. What is New:• Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors.• Public health strategies to improve mental health may be effective in improving HRQOL in children.

Knowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020–2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.

Purpose: Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological and social factors in a large longitudinal population-based sample. Methods: Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort study Ciao Corona in Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc), psychological (sadness, anxiousness, stress) and social (nationality, parents’ education, etc) factors, were assessed in 2020 and 2021, and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level. Results: Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions or nationality, were determinants only in individual subscales. Conclusion: Recent mental health, more than biological, physical or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group. What is known: Assessing health-related quality of life (HRQOL) in children and adolescents aids in under- standing how life circumstances impact their well-being. HRQOL is a complex construct, involving biological, psychological and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples. What is new: Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors. Public health strategies to improve mental health may be effective in improving HRQOL in children.

Objectives To assess the longitudinal development of humoral immunity in children and adolescents during the COVID-19 pandemic, with a particular focus on how anti-spike IgG antibodies and neutralising response changed during the first Omicron peak (December 2021 to May 2022). Design Prospective school-based study during the COVID-19 pandemic (June 2020 to July 2022) including five testing rounds with corresponding cross-sectional cohorts and a longitudinal cohort who participated in at least four rounds. Setting 55 randomly selected schools in the Canton of Zurich, Switzerland. Participants Between 1875 to 2500 children and adolescents per testing round and 751 in the longitudinal cohort. Main outcome measures Development of SARS-CoV-2 seroprevalence, anti-spike IgG antibodies and neutralising antibody response over time, persistence of antibodies and variation of antibody levels in individuals only infected, vaccinated or with hybrid immunity during the early Omicron period. Results By July 2022 96.9% (95% credible interval [CrI] 95.2 to 98.1%) of children and adolescents had anti-spike IgG antibodies against SARS-CoV-2. The substantial increase in seroprevalence during the first peak of the Omicron wave was largely driven by primary infections in mostly unvaccinated children under the age of 12 (28.4% [95% CrI 24.2 to 33.2%] in December 2021, to 95.7% [95% CrI 93.4 to 97.4%] in July 2022). This stands in contrast to adolescents aged 12 years and older (69.4% [95% CrI 64.0 to 75.4%] in December 2021 to 98.4% [95% CrI 97.3 to 99.2%] in July 2022), who were eligible for vaccination since June 2021. Children and adolescents with hybrid immunity or immunity from vaccination had high anti-spike IgG titres (median Mean Fluorescence Intensity (MFI) ratio of 136.2 [Inter Quartile Range [IQR]: 121.9 to 154.3] and 127.6 [IQR: 114.1 to 151.0]) and strong neutralising responses (e.g., anti-Omicron 98.9% [95% Confidence Interval [CI] 96.0 to 99.7%] and 81.6% [95% CI 74.9 to 86.9%]). Meanwhile, infected but unvaccinated children and adolescents had substantially lower anti-spike IgG titres (median MFI ratio of 54.8 [IQR: 22.8 to 89.8]) and neutralising responses (e.g., anti-Omicron 64.9% [95% CI 59.8 to 69.7%]). Conclusion These findings show that the Omicron wave and the rollout of vaccines led to almost 100% seropositivity and boosted anti-spike IgG titres and neutralising capacity in children and adolescents. This was particularly driven by unvaccinated children (<12 years), who became seropositive due to the highly infectious Omicron variant. Nevertheless, during the entire study period parents of only one adolescent reported hospital stay of less than 24 hours related to a possible acute infection.

Objectives Both lifestyle and health-related quality of life (HRQOL) were compromised during the COVID-19 pandemic. We investigated changes in adherence to physical activity and screen time recommendations of children and adolescents throughout the pandemic, and their association with HRQOL. Methods Longitudinal data in 1769 primary (grades 1-6) and secondary (7-9) school children ages 6-17 years was taken from Ciao Corona, a school-based prospective cohort study in Zurich, Switzerland, with 5 online questionnaires between June 2020 and July 2022. HRQOL was assessed using the KINDL questionnaire. Meeting physical activity and screen time recommendations was defined by the world health organization (WHO). Results Adherence to physical activity recommendations dropped in 2020, but returned to pre-pandemic levels by 2022. Fewer children met screen time recommendations in 2020 and 2021 than pre-pandemic. HRQOL reduced 3 points between 2020 and 2022, and was 9.7 points higher (95% CI 3.0 - 16.3) in March 2021 in children who met both recommendations. Conclusions Adherence to WHO guidelines on physical activity and screen time during the pandemic had a consistent association with HRQOL despite longitudinal changes in behavior.