Strategies To Implement SARS-CoV-2 Point-of-Care Testing Into Primary Care Settings: A Qualitative Secondary Analysis Guided By The Behaviour Change Wheel (preprint)

Background: There is little empirical evidence to inform implementation strategies for introducing SARS-CoV-2 point of care (POC) testing into primary care settings. The purpose of this study is to develop a theory-driven understanding of the behavioural determinants underpinning the implementation of SARS-CoV-2 POC testing in primary care. This will allow identification of potential intervention strategies that could encourage successful implementation of testing into routine practice and facilitate face-to-face consultations.Methods: We used a secondary qualitative analysis approach to re-analyse data from a qualitative study that involved interviewing 22 primary care physicians from 21 primary care practices across three regions in England. We followed the three-step method based on the Behaviour Change Wheel to identify barriers/enablers to the implementation of SARS-CoV-2 POC testing and identified behaviour change techniques to inform intervention strategies that targeted the barriers/enablers.Results: We identified 10 barriers and enablers to POC implementation under eight Theoretical Domains Framework (TDF): (1) knowledge; (2) behavioural regulation; (3) reinforcement; (4) skills; (5) environmental context and resources; (6) social influence; (7) professional role and identity; and (8) belief about consequences. Linkages with the Behaviour Change Techniques (BCT) taxonomy enabled the identification of intervention strategies to address the social and contextual factors influencing primary care physician’s willingness and capacity to adopt POC testing.Conclusions: A theory-informed approach identified barriers to the adoption of POC tests in primary care as well as guiding implementation strategies to address these challenges. 

Primary care and point-of-care testing during a pandemic: Clinician's perspectives on integrating rapid testing for COVID-19 into the primary care pathway (preprint)

Background: Real-world evidence to support the adoption of SARS-CoV-2 point-of-care (POC) tests in primary care is limited. As the first point of contact of the health system for most patients, POC testing can potentially support general practitioners (GPs) quickly identify infectious and non-infectious individuals to rapidly inform patient triaging, clinical management, and safely restore more in-person services. Objectives: To explore the potential role of SARS-CoV-2 point-of-care testing in primary care services. Design: A qualitative study using an inductive thematic analysis. Setting: 21 general practices located across three regions in England. Results: Three major themes were identified related to POC test implementation in primary care: (1) Insights into SARS-CoV-2 POC tests; (2) System and organisational factors; and (3) Practice-level service delivery strategies. Thematic subcategories included involvement in rapid testing, knowledge and perception of the current POC testing landscape, capacity for testing, economic concerns, resource necessities, perception of personal risk and safety, responsibility for administering the test, and targeted testing strategies. Conclusion: GPs knowledge of POC tests influences their degree of trust, uncertainty, and their perception of risk of POC test use. Concerns around funding, occupational exposure, and workload play a crucial role in GPs hesitation to provide POC testing services. These concerns could potentially be addressed with government funding, the use of targeted testing, and improved triaging strategies to limit testing to essential patient cohorts.

Perceptions on undertaking regular asymptomatic self-testing for COVID-19 using lateral flow tests: A qualitative study of university students and staff (preprint)

Background There has been an increased interest from governments in implementing mass testing for COVID-19 of asymptomatic individuals using Lateral Flow Tests (LFTs). Successful implementation of such programmes depends on several factors, including feasibility, acceptability and how people act on test results. There is a paucity of studies examining these issues. Objective We aimed to examine experiences of university students and staff with experience of regular asymptomatic self-testing using LFTs, and their subsequent behaviours. Methods We invited people who were participating in a weekly testing feasibility study. We conducted semi-structured remote interviews between December 2020 and January 2021. Additional qualitative data from a survey were also analysed. Data were analysed thematically. Results We interviewed 18 and surveyed 214 participants. Participants were motivated to regularly self-test as they wanted to know whether or not they were infected with SARS-CoV-2. Most reported that a negative test result did not change their behaviour but it did provide them with reassurance to engage with permitted activities. In contrast, some participants reported making decisions about visiting other people when they would not have done so otherwise, because they felt reassured by a negative test result. Participants valued the test training but some participants still doubted their ability to carry out the test. Participants were concerned about safety of attending test sites with lots of people and reported home testing was most convenient. Conclusions If governments want to increase uptake of LFT use, clear messages highlighting the benefits of regular testing for family, friends and society in identifying asymptomatic cases are needed. This should be coupled with transparent communication about accuracy of LFTs and how to act on either a positive or negative result. Concerns about safety, convenience of testing, and ability to do tests need to be addressed to ensure successful scaling up asymptomatic testing.

Predicting COVID-19 related death using the OpenSAFELY platform (preprint)

Objectives To compare approaches for obtaining relative and absolute estimates of risk of 28-day COVID-19 mortality for adults in the general population of England in the context of changing levels of circulating infection. Design Three designs were compared. (A) case-cohort which does not explicitly account for the time-changing prevalence of COVID-19 infection, (B) 28-day landmarking, a series of sequential overlapping sub-studies incorporating time-updating proxy measures of the prevalence of infection, and (C) daily landmarking. Regression models were fitted to predict 28-day COVID-19 mortality. Setting Working on behalf of NHS England, we used clinical data from adult patients from all regions of England held in the TPP SystmOne electronic health record system, linked to Office for National Statistics (ONS) mortality data, using the OpenSAFELY platform. Participants Eligible participants were adults aged 18 or over, registered at a general practice using TPP software on 1st March 2020 with recorded sex, postcode and ethnicity. 11,972,947 individuals were included, and 7,999 participants experienced a COVID-19 related death. The study period lasted 100 days, ending 8th June 2020. Predictors A range of demographic characteristics and comorbidities were used as potential predictors. Local infection prevalence was estimated with three proxies: modelled based on local prevalence and other key factors; rate of A&E COVID-19 related attendances; and rate of suspected COVID-19 cases in primary care. Main outcome measures COVID-19 related death. Results All models discriminated well between patients who did and did not experience COVID-19 related death, with C-statistics ranging from 0.92-0.94. Accurate estimates of absolute risk required data on local infection prevalence, with modelled estimates providing the best performance. Conclusions Reliable estimates of absolute risk need to incorporate changing local prevalence of infection. Simple models can provide very good discrimination and may simplify implementation of risk prediction tools in practice.

Changes in cardiovascular disease monitoring in English primary care during the COVID-19 pandemic: an observational cohort study (preprint)

ObjectiveTo quantify the impact and recovery in cardiovascular disease monitoring in primary care associated with the first COVID-19 lockdown. DesignRetrospective nationwide primary care cohort study, utilising data from 1st January 2018 to 27th September 2020. SettingWe extracted primary care electronic health records data from 514 primary care practices in England contributing to the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID). These practices were representative of English primary care across urban and non-urban practices. ParticipantsThe ORCHID database included 6,157,327 active patients during the study period, and 13,938,390 patient years of observation (final date of follow-up 27th September 2020). The mean (SD) age was 38{+/-}24 years, 49.4% were male and the majority were of white ethnicity (65% [21.9% had unknown ethnicity]) ExposureThe primary exposure was the first national lockdown in the UK, starting on 23rd March 2020. Main outcome measuresRecords of cholesterol, blood pressure, HbA1c and International Normalised Ratio (INR) measurement derived from coded entries in the primary care electronic health record. ResultsRates of cholesterol, blood pressure, HbA1c and INR recording dropped by 23-87% in the week following the first UK national lockdown, compared with the previous week. The largest decline was seen in cholesterol (IRR 0.13, 95% CI 0.11 to 0.15) and smallest for INR (IRR 0.77, 95% CI 0.72 to 0.81). Following the immediate drop, rates of recorded tests increased on average by 5-9% per week until 27th September 2020. However, the number of recorded measures remained below that expected for the time of year, reaching 51.8% (95% CI 51.8 to 51.9%) for blood pressure, 63.7%, (95% CI 63.7% to 63.8%) for cholesterol measurement and 70.3% (95% CI 70.2% to 70.4%) for HbA1c. Rates of INR recording declined throughout the previous two years, a trend that continued after lockdown. There were no differences in the times series trends based on sex, age, ethnicity or deprivation. ConclusionsCardiovascular disease monitoring in English primary care declined substantially from the time of the first UK lockdown. Despite a consistent recovery in activity, there is still a substantial shortfall in the numbers of recorded measurements to those expected. Strategies are required to ensure cardiovascular disease monitoring is maintained during the COVID-19 pandemic.

At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR based tests?: A systematic review of individual participant data (preprint)

STRUCTURED SUMMARYO_ST_ABSBackgroundC_ST_ABSTests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA), using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. MethodsWe conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS- 2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. FindingsOf 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from -6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 to 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post- symptom onset. InterpretationRT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond ten days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias so the positivity rates are probably overestimated. PANEL: RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSThere are numerous reports of negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test results in participants with known SARS-CoV-2 infection, and increasing awareness that the ability of RT-PCR tests to detect virus depends on the timing of sample retrieval and anatomical sampling site. Individual studies suggest that positive test results from RT-PCR with nasopharyngeal sampling declines within a week of symptoms and that a positive test later in the disease course is more likely from sputum, bronchoalveolar lavage (BAL) or stool, but data are inconsistent. Added value of this studyWe searched 5078 titles and abstracts for longitudinal studies reporting individual participant data (IPD) for RT-PCR for participants with COVID-19 linked to either time since symptom onset or time since hospitalisation. Search included SARS-CoV-2 and RT-PCR keywords and MeSH terms. Each included study was subject to careful assessment of risk of bias. This IPD systematic review (SR) addresses RT-PCR test detection rates at different times since symptom onset and hospitalisation for different sampling sites, and summarises the duration of detectable virus. To our knowledge, this is the first rapid SR addressing this topic. We identified 32 studies available as published articles or pre-prints between January 1st and April 24th 2020, including participants sampled at 11 different sampling sites and some participants sampled at more than one site. At earlier time points, nasopharyngeal sampling had the highest virus detection, but the duration of shedding was shorter compared to lower respiratory tract sampling. At 10 to 14 days post-symptom onset, the percentage of positive nasopharyngeal test results was 54% compared to 89% at day 0 to 4. Presence and duration of faecal detection varied by participant, and in nearly half duration was shorter than respiratory sample detection. Virus detection varies for participants and can continue to be detected up to 46 days post-symptom onset or hospitalisation. The included studies were open to substantial risk of bias, so the detection rates are probably overestimates. There was also poor reporting of sampling methods and sparse data on sampling methods that are becoming more widely implemented, such as self-sampling and short nasal swab sampling (anterior nares/mid turbinate). Implications of all the available evidenceResults from this IPD SR of SARS-CoV-2 testing at different time points and using different anatomical sample sites are important to inform strategies of testing. For prevention of ongoing transmission of SARS-CoV-2, samples for RT-PCR testing need to be taken as soon as possible post-symptom onset, as we confirm that RT-PCR misses more people with infection if sampling is delayed. The percentage of positive RT-PCR tests is also highly dependent on the anatomical site sampled in infected people. Sampling at more than one anatomical site may be advisable as there is variation between individuals in the sites that are infected, as well as the timing of SARS-CoV-2 virus detection at an anatomical site. Testing ten days after symptom onset will lead to a higher frequency of negative tests, particularly if using only upper respiratory tract sampling. However, our estimates may considerably understate the frequency of negative RT-PCR results in people with SARS-CoV- 2 infection. Further investment in this IPD approach is recommended as the amount data available was small given the scale of the pandemic and the importance of the question. More studies, learning from our observations about risk of bias and strengths of example studies (Box 1, Box 2) are urgently needed to inform the optimal sampling strategy by including self-collected samples such as saliva and short nasal swabs. Better reporting of anatomical sampling sites with a detailed methodology on sample collection is also urgently needed.