Inpatient care utilisation and expenditure associated with objective physical activity:econometric analysis of the UK Biobank

BACKGROUND Physical inactivity increases the risk of chronic disease and mortality. The high prevalence of physical inactivity in the UK is likely to increase financial pressure on the National Health Service. The UK Biobank Study offered an opportunity to assess the impact of physical inactivity on healthcare use and spending using individual-level data and objective measures of physical activity. The objective of this study was to assess the associations between objectively measured physical activity levels and future inpatient days and costs in adults in the UK Biobank study. METHODS We conducted an econometric analysis of the UK Biobank study, a large prospective cohort study. The participants (n = 86,066) were UK adults aged 43-79 who had provided sufficient valid accelerometer data. Hospital inpatient days and costs were discounted and standardised to mean monthly values per person to adjust for the variation in follow-up times. Econometric models adjusted for BMI, long-standing illness, and other sociodemographic factors. RESULTS Mean follow-up time for the sample was 28.11 (SD 7.65) months. Adults in the most active group experienced 0.037 fewer days per month (0.059-0.016) and 14.1% lower inpatient costs ( - £3.81 [ - £6.71 to  - £0.91] monthly inpatient costs) compared to adults in the least active group. The relationship between physical activity and inpatient costs was stronger in women compared to men and amongst those in the lowest income group compared to others. The findings remained significant across various sensitivity analyses. CONCLUSIONS Increasing physical activity levels in the UK may reduce inpatient hospitalisations and costs, especially in women and lower-income groups

Social contacts and attitudes towards vaccination during the COVID-19 pandemic: Insights from the CoMix study.

During the coronavirus disease 2019 (COVID-19) pandemic, individuals adapted their patterns of social contact to avoid pathogen exposure and due to government restrictions that aimed to slow down disease transmission. Studying the changing social contact patterns during the pandemic can play an important role to improve future pandemic responses. Furthermore, a better understanding of COVID-19 vaccination uptake and attitudes towards vaccination in different age and socioeconomic groups can help inform vaccination strategies. CoMix is a social contact survey that follows households across Europe in real-time over the course of the COVID-19 pandemic. In Switzerland, we conducted the CoMix study over 24 survey waves from January 2021 to May 2022. Across all survey waves and participants, the average number of reported contacts was 4.8 per day. The number of contacts were highest in the age group of 0-18 year olds and lowest in people who are 65 or older. The survey captured the vaccination uptake in the general population well and participants provided detailed insights into their reasons to get vaccinated and to not get vaccinated. The CoMix study provides the first detailed data on social contact patterns in Switzerland. The results from the study can be used to improve pandemic preparedness, parameterize mathematical models of infectious disease transmission, and design future vaccination strategies

Contact tracing for COVID-19 in a Swiss canton: analysis of key performance indicators.

BACKGROUND Contact tracing (CT) has played an important role in strategies to control COVID-19. However, there is limited evidence on the performance of digital tools for CT and no consensus on which indicators to use to monitor their performance. We aimed to describe the system and analyse outcomes of CT with a partially automated workflow in the Swiss canton of Solothurn, using key performance indicators (KPIs). METHODS We describe the process of CT used in the canton of Solothurn between November 2020 and February 2022, including forward and backward CT. We developed 16 KPIs representing CT structure (S1-2), process (P1-11) and outcome (O1-3) based on previous literature to analyse the relative performance of CT. We report the changes in the indicators over waves of SARS-CoV-2 infections caused by several viral variants. RESULTS The CT team in Solothurn processed 57,363 index cases and 71,809 contacts over a 15-month period. The CT team successfully contacted 99% of positive cases within 24 hours (KPI P7) throughout the pandemic and returned almost all test results on the same or next day (KPI P6), before the delta variant emerged. Three-quarters of contacts were notified within 24 hours of the CT interview with the index (KPI P8) before the emergence of the alpha, delta and omicron variants, when the proportions decreased to 64%, 36% and 54%, respectively. The percentage of new symptomatic cases tested and interviewed within 3 days of symptom onset was high at >70% (KPI P10) and contacts started quarantine within a median of 3 days of index case symptom onset (KPI P3). About a fifth of new index cases had already been in quarantine by the time of their positive test (KPI O1), before the delta variant emerged. The percentage of index cases in isolation by day of testing remained at almost 100% throughout the period of analysis (KPI O2). CONCLUSIONS The CT in Solothurn used a partially automated workflow and continued to perform well throughout the pandemic, although the relative performance of the CT system declined at higher caseloads. CT remains an important tool for controlling the spread of infectious diseases, but clearer standards should improve the performance, comparability and monitoring of infection in real time as part of pandemic preparedness efforts

Socio-demographic characteristics associated with COVID-19 vaccination uptake in Switzerland: longitudinal analysis of the CoMix study.

BACKGROUND Vaccination is an effective strategy to reduce morbidity and mortality from coronavirus disease 2019 (COVID-19). However, the uptake of COVID-19 vaccination has varied across and within countries. Switzerland has had lower levels of COVID-19 vaccination uptake in the general population than many other high-income countries. Understanding the socio-demographic factors associated with vaccination uptake can help to inform future vaccination strategies to increase uptake. METHODS We conducted a longitudinal online survey in the Swiss population, consisting of six survey waves from June to September 2021. Participants provided information on socio-demographic characteristics, history of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), social contacts, willingness to be vaccinated, and vaccination status. We used a multivariable Poisson regression model to estimate the adjusted rate ratio (aRR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake. RESULTS We recorded 6,758 observations from 1,884 adults. For the regression analysis, we included 3,513 observations from 1,883 participants. By September 2021, 600 (75%) of 806 study participants had received at least one vaccine dose. Participants who were older, male, and students, had a higher educational level, household income, and number of social contacts, and lived in a household with a medically vulnerable person were more likely to have received at least one vaccine dose. Female participants, those who lived in rural areas and smaller households, and people who perceived COVID-19 measures as being too strict were less likely to be vaccinated. We found no significant association between previous SARS-CoV-2 infections and vaccination uptake. CONCLUSIONS Our results suggest that socio-demographic factors as well as individual behaviours and attitudes played an important role in COVID-19 vaccination uptake in Switzerland. Therefore, appropriate communication with the public is needed to ensure that public health interventions are accepted and implemented by the population. Tailored COVID-19 vaccination strategies in Switzerland that aim to improve uptake should target specific subgroups such as women, people from rural areas or people with lower socio-demographic status

How to update a living systematic review and keep it alive during a pandemic: a practical guide.

BACKGROUND The covid-19 pandemic has highlighted the role of living systematic reviews. The speed of evidence generated during the covid-19 pandemic accentuated the challenges of managing high volumes of research literature. METHODS In this article, we summarise the characteristics of ongoing living systematic reviews on covid-19, and we follow a life cycle approach to describe key steps in a living systematic review. RESULTS We identified 97 living systematic reviews on covid-19, published up to 7th November 2022, which focused mostly on the effects of pharmacological interventions (n = 46, 47%) or the prevalence of associated conditions or risk factors (n = 30, 31%). The scopes of several reviews overlapped considerably. Most living systematic reviews included both observational and randomised study designs (n = 45, 46%). Only one-third of the reviews has been updated at least once (n = 34, 35%). We address practical aspects of living systematic reviews including how to judge whether to start a living systematic review, methods for study identification and selection, data extraction and evaluation, and give recommendations at each step, drawing from our own experience. We also discuss when it is time to stop and how to publish updates. CONCLUSIONS Methods to improve the efficiency of searching, study selection, and data extraction using machine learning technologies are being developed, their performance and applicability, particularly for reviews based on observational study designs should improve, and ways of publishing living systematic reviews and their updates will continue to evolve. Finally, knowing when to end a living systematic review is as important as knowing when to start

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections : update of a living systematic review and meta-analysis

Funding: This study was funded by the Swiss National Science Foundation http://www.snf.ch/en (NL: 320030_176233); the European Union Horizon 2020 research and innovation programme https://ec.europa.eu/programmes/horizon2020/en (NL: 101003688); the Swiss government excellence scholarship https://www.sbfi.admin.ch/sbfi/en/home/education/scholarships-and-grants/swiss-government-excellence-scholarships.html (DBG: 2019.0774) and the Swiss School of Public Health Global P3HS stipend https://ssphplus.ch/en/ (DBG).Background : Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? Methods and findings : The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. Conclusions : Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. Review protocol : Open Science Framework (https://osf.io/9ewys/)Publisher PDFPeer reviewe

A quantitative PCR (TaqMan) assay for pathogenic Leptospira spp

BACKGROUND: Leptospirosis is an emerging infectious disease. The differential diagnosis of leptospirosis is difficult due to the varied and often "flu like" symptoms which may result in a missed or delayed diagnosis. There are over 230 known serovars in the genus Leptospira. Confirmatory serological diagnosis of leptospirosis is usually made using the microscopic agglutination test (MAT) which relies on the use of live cultures as the source of antigen, often performed using a panel of antigens representative of local serovars. Other techniques, such as the enzyme linked immunosorbent assay (ELISA) and slide agglutination test (SAT), can detect different classes of antibody but may be subject to false positive reactions and require confirmation of these results by the MAT. METHODS: The polymerase chain reaction (PCR) has been used to detect a large number of microorganisms, including those of clinical significance. The sensitivity of PCR often precludes the need for isolation and culture, thus making it ideal for the rapid detection of organisms involved in acute infections. We employed real-time (quantitative) PCR using TaqMan chemistry to detect leptospires in clinical and environmental samples. RESULTS AND CONCLUSIONS: The PCR assay can be applied to either blood or urine samples and does not rely on the isolation and culture of the organism. Capability exists for automation and high throughput testing in a clinical laboratory. It is specific for Leptospira and may discriminate pathogenic and non-pathogenic species. The limit of detection is as low as two cells

Advocating for implementation of the Global Action Plan on Physical Activity: challenges and support requirements

Background: There is limited understanding of the challenges experienced and supports required to aid effective advocacy of the Global Action Plan on Physical Activity (GAPPA). The purpose of this study was to assess the challenges experienced and supports needed to advocate for the GAPPA across countries of different income levels. Methods: Stakeholders working in an area related to the promotion of physical activity were invited to complete an online survey. The survey assessed current awareness and engagement with the GAPPA, factors related to advocacy, and the perceived challenges and supports related to advocacy for implementation of the GAPPA. Closed questions were analyzed in SPSS, with a Pearson’s chi-square test used to assess differences between country income level. Open questions were analyzed using inductive thematic analysis. Results: Participants (n = 518) from 81 countries completed the survey. Significant differences were observed between country income level for awareness of the GAPPA and perceived country engagement with the GAPPA. Challenges related to advocacy included a lack of support and engagement, resources, priority, awareness, advocacy education and training, accessibility, and local application. Supports needed for future advocacy included guidance and support, cooperation and alliance, advocacy education and training, and advocacy resources. Conclusions: Although stakeholders from different country income levels experience similar advocacy challenges and required supports, how countries experience these can be distinct. This research has highlighted some specific ways in which those involved in the promotion of physical activity can be supported to scale up advocacy for the GAPPA. When implementing such supports, consideration of regional, geographic, and cultural barriers and opportunities is important to ensure they are effective and equitable

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes