Rapid diagnostic tests (RDTs) developed for point of care detection of SARS-CoV-2 antigen are recommended by WHO to use trained health care workers to collect samples. We hypothesised that self-taken ...samples are non-inferior for use with RDTs to diagnose COVID-19. We designed a prospective diagnostic evaluation comparing self-taken and healthcare worker (HCW)-taken throat/nasal swabs to perform RDTs for SARS-CoV-2, and how these compare to RT-PCR.
Eligible participants 18 years or older with symptoms of COVID-19. 250 participants recruited at the NHS Test and Trace drive-through community PCR testing site (Liverpool, UK); one withdrew before analysis. Self-administered throat/nasal swab for the Covios® RDT, a trained HCW taken throat/nasal sample for PCR and HCW comparison throat/nasal swab for RDT were collected. RDT results were compared to RT-PCR, as the reference standard, to calculate sensitivity and specificity.
Seventy-five participants (75/249, 30.1%) were positive by RT-PCR. RDTs with self-taken swabs had a sensitivity of 90.5% (67/74, 95% CI: 83.9-97.2), compared to 78.4% (58/74, 95% CI: 69.0-87.8) for HCW-taken swabs (absolute difference 12.2%, 95% CI: 4.7-19.6, p = 0.003). Specificity for self-taken swabs was 99.4% (173/174, 95% CI: 98.3-100.0), versus 98.9% (172/174, 95% CI: 97.3-100.0) for HCW-taken swabs (absolute difference 0.6%, 95% CI: 0.5-1.7, p = 0.317). The PPV of self-taken RDTs (98.5%, 67/68, 95% CI: 95.7-100.0) and HCW-taken RDTs (96.7%, 58/60, 95% CI 92.1-100.0) were not significantly different (p = 0.262). However, the NPV of self-taken swab RDTs was significantly higher (96.1%, 173/180, 95% CI: 93.2-98.9) than HCW-taken RDTs (91.5%, 172/188, 95% CI 87.5-95.5, p = 0.003).
In conclusion, self-taken swabs for COVID-19 testing offer an accurate alternative to healthcare worker taken swabs for use with RDTs. Our results demonstrate that, with no training, self-taken throat/nasal samples can be used by lay individuals as part of rapid testing programmes for symptomatic adults. This is especially important where the lack of trained healthcare workers restricts access to testing.
Point of care blood testing to aid diagnosis is becoming increasingly common in acute ambulatory settings and enables timely investigation of a range of diagnostic markers. However, this testing ...allows scope for errors in the pre-analytical phase, which depends on the operator handling and transferring specimens correctly. The extent and nature of these pre-analytical errors in clinical settings has not been widely reported.
We carried out a convergent parallel mixed-methods service evaluation to investigate pre-analytical errors leading to a machine error reports in a large acute hospital trust in the UK. The quantitative component comprised a retrospective analysis of all recorded error codes from Abbott Point of Care i-STAT 1, i-STAT Alinity and Abbott Rapid Diagnostics Afinion devices to summarise the error frequencies and reasons for error, focusing on those attributable to the operator. The qualitative component included a prospective ethnographic study and a secondary analysis of an existing ethnographic dataset, based in hospital-based ambulatory care and community ambulatory care respectively.
The i-STAT had the highest usage (113,266 tests, January 2016-December 2018). As a percentage of all tests attempted, its device-recorded overall error rate was 6.8% (95% confidence interval 6.6% to 6.9%), and in the period when reliable data could be obtained, the operator-attributable error rate was 2.3% (2.2% to 2.4%). Staff identified that the most difficult step was the filling of cartridges, but that this could be improved through practice, with a perception that cartridge wastage through errors was rare.
In the observed settings, the rate of errors attributable to operators of the primary point of care device was less than 1 in 40. In some cases, errors may lead to a small increase in resource use or time required so adequate staff training is necessary to prevent adverse impact on patient care.
Abstract
Objectives
Given the lack of accurate rapid diagnostics for urinary tract infection (UTI) in women, many countries have developed guidelines aiming to support appropriate antibiotic ...prescribing, but some guidelines have not been validated. We performed a diagnostic accuracy validation study of two guidelines: Public Health England (GW-1263) and Scottish Intercollegiate Guidelines Network (SIGN160).
Methods
We used data from women with symptoms suggestive of uncomplicated UTI from a randomized controlled trial comparing urine collection devices. Symptom information was recorded via baseline questionnaire and primary care assessment. Women provided urine samples for dipstick testing and culture. We calculated the number within each risk category of diagnostic flowcharts who had positive/mixed growth/no significant growth urine culture. Results were presented as positive/negative predictive values, with 95% CIs.
Results
Of women aged under 65 years, 311/509 (61.1%, 95% CI 56.7%–65.3%) classified to the highest risk category (recommended to consider immediate antibiotic prescribing) and 80/199 (40.2%, 95% CI 33.4%–47.4%) classified to the lowest risk category (recommended to reassure that UTI is less likely) by the GW-1263 guideline (n = 810) had positive culture. For the SIGN160 guideline (n = 814), the proportion with positive culture ranged from 60/82 (73.2%, 95% CI 62.1%–82.1%) in those for whom immediate treatment was indicated to 33/76 (43.4%, 95% CI 32.3%–55.3%) in those recommended a self-care/waiting strategy.
Conclusions
Clinicians should be aware of the potential for diagnostic error when using diagnostic guidelines for managing uncomplicated UTI and making antimicrobial prescribing decisions. Infection cannot be excluded on the basis of symptoms and dipstick testing alone.
Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic ...accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care.
Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups.
Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms.
Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile's minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced.
ISRCTN142269.
Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidence base to guide interventions against this major public health concern is small. We aimed to ...investigate possible drivers of changes in the incidence of E coli bloodstream infection and antibiotic susceptibilities in Oxfordshire, UK, over the past two decades, while stratifying for time since hospital exposure.
In this observational study, we used all available data on E coli bloodstream infections and E coli urinary tract infections (UTIs) from one UK region (Oxfordshire) using anonymised linked microbiological data and hospital electronic health records from the Infections in Oxfordshire Research Database (IORD). We estimated the incidence of infections across a two decade period and the annual incidence rate ratio (aIRR) in 2016. We modelled the data using negative binomial regression on the basis of microbiological, clinical, and health-care-exposure risk factors. We investigated infection severity, 30-day all-cause mortality, and community and hospital amoxicillin plus clavulanic acid (co-amoxiclav) use to estimate changes in bacterial virulence and the effect of antimicrobial resistance on incidence.
From Jan 1, 1998, to Dec 31, 2016, 5706 E coli bloodstream infections occurred in 5215 patients, and 228 376 E coli UTIs occurred in 137 075 patients. 1365 (24%) E coli bloodstream infections were nosocomial (onset >48 h after hospital admission), 1132 (20%) were quasi-nosocomial (≤30 days after discharge), 1346 (24%) were quasi-community (31–365 days after discharge), and 1863 (33%) were community (>365 days after hospital discharge). The overall incidence increased year on year (aIRR 1·06, 95% CI 1·05–1·06). In 2016, 212 (41%) of 515 E coli bloodstream infections and 3921 (28%) of 13 792 E coli UTIs were co-amoxiclav resistant. Increases in E coli bloodstream infections were driven by increases in community (aIRR 1·10, 95% CI 1·07–1·13; p<0·0001) and quasi-community (aIRR 1·08, 1·07–1·10; p<0·0001) cases. 30-day mortality associated with E coli bloodstream infection decreased over time in the nosocomial (adjusted rate ratio RR 0·98, 95% CI 0·96–1·00; p=0·03) group, and remained stable in the quasi-nosocomial (adjusted RR 0·98, 0·95–1·00; p=0·06), quasi-community (adjusted RR 0·99, 0·96–1·01; p=0·32), and community (adjusted RR 0·99, 0·96–1·01; p=0·21) groups. Mortality was, however, substantial at 14–25% across all hospital-exposure groups. Co-amoxiclav-resistant E coli bloodstream infections increased in all groups across the study period (by 11–18% per year, significantly faster than co-amoxiclav-susceptible E coli bloodstream infections; pheterogeneity<0·0001), as did co-amoxiclav-resistant E coli UTIs (by 14–29% per year; pheterogeneity<0·0001). Previous year co-amoxiclav use in primary-care facilities was associated with increased subsequent year community co-amoxiclav-resistant E coli UTIs (p=0·003).
Increases in E coli bloodstream infections in Oxfordshire are primarily community associated, with substantial co-amoxiclav resistance; nevertheless, we found little or no change in mortality. Focusing interventions on primary care facilities, particularly those with high co-amoxiclav use, could be effective in reducing the incidence of co-amoxiclav-resistant E coli bloodstream infections, in this region and more generally.
National Institute for Health Research.
One approach to improving antibiotic stewardship in primary care may be to support all General Practitioners (GPs) to have access to point of care C-Reactive Protein tests to guide their prescribing ...decisions in patients presenting with symptoms of lower respiratory tract infection. However, to date there has been no work to understand how clinical commissioning groups might approach the practicalities of system-wide implementation. We aimed to develop an accessible service delivery modelling tool that, based on open data, could generate a layout of the geographical distribution of point of care facilities that minimised the cost and travel distance for patients across a given region. We considered different implementation models where point of care tests were placed at either GP surgeries, pharmacies or both. We analysed the trade-offs between cost and travel found by running the model under different configurations and analysing the model results in four regions of England (two urban, two rural). Our model suggests that even under assumptions of short travel distances for patients (e.g. under 500m), it is possible to achieve a meaningful reduction in the number of necessary point of care testing facilities to serve a region by referring some patients to be tested at nearby GP surgeries or pharmacies. In our test cases pharmacy-led implementation models resulted in some patients having to travel long distances to obtain a test, beyond the desired travel limits. These results indicate that an efficient implementation strategy for point of care tests over a geographic region, potentially building on primary care networks, might lead to significant cost reduction in equipment and associated personnel training, maintenance and quality control costs; as well as achieving fair access to testing facilities.
We aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia.
Cross-sectional study among ...people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART).
We used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia at least 1000 copies/ml using logistic regression models. In exploratory analyses, we used receiver operating curves (ROCs) to estimate optimal urine TFV and DBS TFV-DP thresholds to predict concurrent viraemia.
Among 124 participants, 68 (54.8%) were women, median age was 39 years interquartile range (IQR) 34-45 and 74 (59.7%) were receiving efavirenz versus 50 (40.3%) receiving dolutegravir. Higher concentrations of urine TFV 1000 ng/ml increase, odds ratio (OR) 0.97 95% CI 0.94-0.99, P = 0.005 and DBS TFV-DP (100 fmol/punch increase, OR 0.76, 95% CI 0.67-0.86, P < 0.001) were associated with lower odds of viraemia. There was evidence that these associations were stronger among people receiving dolutegravir than among people receiving efavirenz (urine TFV, P = 0.072; DBS TFV-DP, P = 0.003). Nagelkerke pseudo- R2 for the DBS TFV-DP models was higher for the urine TFV models, demonstrating a stronger relationship between DBS TFV-DP and viraemia. Among people receiving dolutegravir, a DBS TFV-DP concentration of 483 fmol/punch had 88% sensitivity and 85% specificity to predict concurrent viraemia ≥1000 copies/ml.
Among PWH receiving TDF-based ART, urine TFV concentrations, and in particular DBS TFV-DP concentrations, were strongly associated with concurrent viraemia, especially among people receiving dolutegravir.
Cellulitis is often treated with antibiotics for longer than recommended by guidelines. Prolonged therapy may reduce recurrence in certain patients, but it is not known which patients are at greatest ...risk. Our objective was to develop and temporally validate a risk prediction score to identify patients attending hospital with cellulitis at highest risk of recurrence.
We included UK adult patients with cellulitis attending hospital in an electronic health records (EHR) study to identify demographic, comorbid, physiological, and laboratory factors predicting recurrence (before death) within 90 days, using multivariable logistic regression with backwards elimination in complete cases. A points-based risk score integerised model coefficients for selected predictors. Performance was assessed using the C-index in development and temporal validation samples.
The final model included 4938 patients treated for median 8 days (IQR 6-11); 8.8% (n = 436) experienced hospitalisation-associated recurrence. A risk score using eight variables (age, heart rate, urea, platelets, albumin, previous cellulitis, venous insufficiency, and liver disease) ranged from 0-15, with C-index = 0.65 (95%CI: 0.63-0.68). Categorising as low (score 0-1), medium (2-5) and high (6-15) risk, recurrence increased fourfold; 3.2% (95%CI: 2.3-4.4%), 9.7% (8.7-10.8%), and 16.6% (13.3-20.4%). Performance was maintained in the validation sample (C-index = 0.63 (95%CI: 0.58-0.67)). Among patients at high risk, four distinct clinical phenotypes were identified using hierarchical clustering 1) young, acutely unwell with liver disease; 2) comorbid with previous cellulitis and venous insufficiency; 3) chronic renal disease with severe renal impairment; and 4) acute severe illness, with substantial inflammatory responses.
Risk of cellulitis recurrence varies markedly according to individual patient factors captured in the Baseline Recurrence Risk in Cellulitis (BRRISC) score. Further work is needed to optimise the score, considering baseline and treatment response variables not captured in EHR data, and establish the utility of risk-based approaches to guide optimal antibiotic duration.
•Antibiotic treatment of cellulitis aims to achieve sustained, recurrence-free cure.•Baseline patient factors at diagnosis are associated with risk of recurrence.•Antibiotic duration exceeds guidelines even in patients at very low risk.•Risks are associated with ageing, immune defects, renal disease and severe illness.•A points-based risk score using 8 items is proposed with moderate performance.
Paediatric consultations form a significant proportion of all consultations in ambulatory care. Point-of-care tests (POCTs) may offer a potential solution to improve clinical outcomes for children by ...reducing diagnostic uncertainty in acute illness, and streamlining management of chronic diseases. However, their clinical impact in paediatric ambulatory care is unknown. We aimed to describe the clinical impact of all in-vitro diagnostic POCTs on patient outcomes and healthcare processes in paediatric ambulatory care.
We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from inception to 29 January 2020 without language restrictions. We included studies of children presenting to ambulatory care settings (general practice, hospital outpatient clinics, or emergency departments, walk-in centres, registered drug shops delivering healthcare) where in-vitro diagnostic POCTs were compared to usual care. We included all quantitative clinical outcome data across all conditions or infection syndromes reporting on the impact of POCTs on clinical care and healthcare processes. Where feasible, we calculated risk ratios (RR) with 95% confidence intervals (CI) by performing meta-analysis using random effects models.
We included 35 studies. Data relating to at least one outcome were available for 89,439 children of whom 45,283 had a POCT across six conditions or infection syndromes: malaria (n = 14); non-specific acute fever 'illness' (n = 7); sore throat (n = 5); acute respiratory tract infections (n = 5); HIV (n = 3); and diabetes (n = 1). Outcomes centred around decision-making such as prescription of medications or hospital referral. Pooled estimates showed that malarial-POCTs (Plasmodium falciparum) better targeted antimalarial treatment by reducing over-treatment by a third compared to usual care (RR 0.67; 95% CI 0.58 to 0.77, n = 36,949). HIV-POCTs improved initiating earlier antiretroviral therapy compared to usual care (RR, 3.11; 95% CI 1.55 to 6.25, n = 912). Across the other four conditions, there was limited evidence for the benefit of POCTs in paediatric ambulatory care except for acute respiratory tract infections (RTI) in low-and-middle-income countries (LMICs), where POCT C-Reactive Protein (CRP) may reduce immediate antibiotic prescribing by a third (risk difference, -0.29 -0.47, -0.11, n = 2,747). This difference was shown in randomised controlled trials in LMICs which included guidance on interpretation of POCT-CRP, specific training or employed a diagnostic algorithm prior to POC testing.
Overall, there is a paucity of evidence for the use of POCTs in paediatric ambulatory care. POCTs help to target prescribing for children with malaria and HIV. There is emerging evidence that POCT-CRP may better target antibiotic prescribing for children with acute RTIs in LMIC, but not in high-income countries. Research is urgently needed to understand where POCTs are likely to improve clinical outcomes in paediatric settings worldwide.
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