Search

BackgroundLower urinary tract symptoms (LUTS) are common in males aged ≥40 years and have a considerable impact on quality of life. Management can be complex, and although most LUTS could be treated effectively in primary care, referrals to urology outpatients are increasing.AimTo explore GPs’ experiences of managing LUTS together with patients’ experiences of and preferences for treatment in primary care.Design and settingTelephone interviews were conducted with GPs and male patients presenting to primary care with bothersome LUTS.MethodEleven GPs and 25 male patients were purposively sampled from 20 GP practices in three UK regions: Newcastle upon Tyne, Bristol, and South Wales. Interviews were conducted between May 2018 and January 2019, and were analysed using a framework approach.ResultsDifficulty establishing causes and differentiating between prostate and bladder symptoms were key challenges to the diagnosis of LUTS in primary care, often making treatment a process of trial and error. Pharmacological treatments were commonly ineffective and often caused side effects. Despite this, patients were generally satisfied with GP consultations and expressed a preference for treatment in primary care.ConclusionManaging LUTS in primary care is a more accessible option for patients. Given the challenges of LUTS diagnosis, an effective diagnostic tool for use by GPs would be beneficial. Ensuring bothersome LUTS are not dismissed as a normal part of ageing is essential in improving patients’ quality of life. Greater exploration of the role of non-pharmacological treatments is needed.

Introduction Care home residents are at high risk of dying from coronavirus disease 2019 (COVID-19). Regular testing, producing rapid and reliable results is important in this population because infections spread quickly, and presentations are often atypical or asymptomatic. This study evaluated current testing pathways in care homes to explore the role of point-of-care tests (POCTs). Methods A total of 10 staff from eight care homes, purposively sampled to reflect care organisational attributes that influence outbreak severity, underwent a semi-structured remote videoconference interview. Transcripts were analysed using process mapping tools and framework analysis focussing on perceptions about, gaps within and needs arising from current pathways. Results Four main steps were identified in testing: infection prevention, preparatory steps, swabbing procedure and management of residents. Infection prevention was particularly challenging for mobile residents with cognitive impairment. Swabbing and preparatory steps were resource-intensive, requiring additional staff resource. Swabbing required flexibility and staff who were familiar to the resident. Frequent approaches to residents were needed to ensure they would participate at a suitable time. After-test management varied between sites. Several homes reported deviating from government guidance to take more cautious approaches, which they perceived to be more robust. Conclusion Swab-based testing is organisationally complex and resource-intensive in care homes. It needs to be flexible to meet the needs of residents and provide care homes with rapid information to support care decisions. POCT could help address gaps but the complexity of the setting means that each technology must be evaluated in context before widespread adoption in care homes.

BackgroundTests 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.ResultsOf 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 and 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.ConclusionsRT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 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.

Respiratory syncytial virus is a common cause of bronchiolitis. Historically, point-of-care tests have involved antigen detection technology with limited sensitivity. The aim of this study was to prospectively evaluate the diagnostic accuracy and model the economic impact of the Roche cobas® Liat® point-of-care influenza A/B and respiratory syncytial virus test. The “DEC-RSV” study was a multi-centre, prospective, observational study in children under 2 years presenting with viral respiratory symptoms. A nasopharyngeal aspirate sample was tested using the point-of-care test and standard laboratory-based procedures. The primary outcome was accuracy of respiratory syncytial virus detection. The cost implications of adopting a point-of-care test were modelled using study data. A total of 186 participants were recruited, with both tests performed on 177 samples. The point-of-care test was invalid for 16 samples (diagnostic yield 91%) leaving 161 available for primary analysis. After resolving discrepancies, the cobas® Liat® respiratory syncytial virus test had 100.00% (95% CI 96.07%–100.00%) sensitivity and 98.53% (95% CI 92.08%–99.96%) specificity. Median time to result was 0.6 h (interquartile range (IQR) 0.5–1) for point-of-care testing and 28.9 h (IQR 26.3–48.1) for standard laboratory testing. Estimated non-diagnostic cost savings for 1000 patients, based on isolation decision-making on point-of-care test result, were £57 010, which would increase to £94 847 when cohort nursing is used. In young children the cobas® Liat® point-of-care respiratory syncytial virus test has high diagnostic accuracy using nasopharyngeal aspirates (currently an off-licence sample type). Time to result is clinically important and was favourable compared to laboratory-based testing. The potential exists for cost savings when adopting the point-of-care test., This prospective evaluation of the cobas Liat point-of-care RSV test in children demonstrated high diagnostic accuracy using nasopharyngeal aspirate samples, with favourable time to result compared to usual laboratory-based testing procedures https://bit.ly/2yKKmUB

Objectives The second wave of the coronavirus pandemic is now established, occurring at a time of winter pressure on acute care in the NHS. This is likely to be more challenging then the first wave for the diagnosis of COVID-19 because of the similar symptomology with other respiratory conditions highly prevalent in winter. This study sought to understand the care pathways in place in UK NHS hospitals during the first wave (March–July 2020) for identification of patients with COVID-19 and to learn lessons to inform optimal testing strategies within the COVID-19 National Diagnostic Research and Evaluation Platform (CONDOR). Design, setting & participants Sixteen hospital-based clinicians from 12 UK NHS Trusts covering 10 different specialties were interviewed following a semi-structured topic guide. Data were coded soon after the interviews and analysed thematically. Results We developed a diagrammatic, high-level visualisation of the care pathway describing the main clinical decisions associated with the diagnosis and management of patients with suspected COVID-19. COVID-19 testing influenced infection control considerations more so than treatment decisions. Two main features of service provision influenced the patient management significantly: access to rapid laboratory testing and the number of single occupancy rooms. If time to return of result was greater than 24 h, patients with a presumptive diagnosis would often be cohorted based on clinical suspicion alone. Undetected COVID-19 during this time could therefore lead to an increased risk of viral transmission. Conclusions During the winter months, priority for provision of rapid testing at admission should be given to hospitals with limited access to laboratory services and single room availability. Access to rapid testing is essential for urgent decisions related to emergency surgery, maternity services and organ transplant. The pathway and prioritization of need will inform the economic modelling, clinical evaluations, and implementation of new clinical tests in UK.

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work. A systematic literature review and meta-analysis were performed. The search included names of commonly used, routine laboratory tests in the UK NHS, and focused on research papers reporting laboratory results of patients diagnosed with COVID-19. A random effects meta-analysis of the standardized mean difference between COVID-19-positive and -negative groups was conducted for each biomarker. When comparing reported laboratory biomarker results, we identified decreased white blood cell, neutrophil, lymphocyte, eosinophil, and platelet counts; while lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were elevated in COVID-19-positive compared to COVID-19-negative patients. Differences were identified across a number of routine laboratory biomarkers between COVID-19-positive and -negative patients. Further research is required to identify whether routine laboratory biomarkers can be used in the development of a clinical scoring system to aid with triage of patients.

IntroductionLower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care.Methods and analysisPRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool.Ethics and disseminationEthics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders.Trial registration numberISRCTN10327305.

Background: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia.Methods: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425.Findings: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes.Interpretation: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect.Funding: UK Department of Health and the Wellcome Trust.

The Receiver Operating Characteristic (ROC) curve and the Area Under the Curve (AUC) of the ROC curve are widely used in discovery to compare the performance of diagnostic and prognostic assays. The ROC curve has the advantage that it is independent of disease prevalence. However, in this note, we remind scientists and clinicians that the performance of an assay upon translation to the clinic is critically dependent upon that very same prevalence. Without an understanding of prevalence in the test population, even robust bioassays with excellent ROC characteristics may perform poorly in the clinic. While the exact prevalence in the target population is not always known, simple plots of candidate assay performance as a function of prevalence rate give a better understanding of the likely real-world performance and a greater understanding of the likely impact of variation in that prevalence on translation to the clinic.

ObjectiveTo assess the value added to the National Early Warning Score (NEWS) by mid-regional pro-adrenomedullin (MR-proADM) blood level in predicting deterioration in mild to moderately ill people.DesignProspective observational study.SettingThe Medical Admissions Suite of the Royal Victoria Infirmary, Newcastle.Participants300 adults with NEWS between 2 and 5 on admission. Exclusion criteria included receiving palliative care, or admitted for social reasons or self-harming. Patients were enrolled between September and December 2015, and followed up for 30 days after discharge.Outcome measureThe primary outcome measure was the proportion of patients who, within 72 hours, had anacuity increase, defined as any combination of an increase of at least 2 in the NEWS; transfer to a higher-dependency bed or monitored area; death; or for those discharged from hospital, readmission for medical reasons.ResultsNEWS and MR-proADM together predictedacuity increasemore accurately than NEWS alone, increasing the area under the curve (AUC) to 0.61 (95% CI 0.54 to 0.69) from 0.55 (95% CI 0.48 to 0.62). When the confounding effects of presence of chronic obstructive pulmonary disease or heart failure and interaction with MR-proADM were included, the prognostic accuracy further increased the AUC to 0.69 (95% CI 0.63 to 0.76).ConclusionsMR-proADM is potentially a clinically useful biomarker for deterioration in patients admitted to hospital with a mild to moderately severe acute illness, that is, with NEWS between 2 and 5. As a growing number of National Health Service hospitals are routinely recording the NEWS on their clinical information systems, further research should assess the practicality and use of developing a decision aid based on admission NEWS, MR-proADM level, and possibly other clinical data and other biomarkers that could further improve prognostic accuracy.

There is an urgent requirement to identify which clinical settings are in most need of COVID-19 tests and the priority role(s) for tests in these settings to accelerate the development of tests fit for purpose in health and social care across the UK. This study sought to identify and prioritize unmet clinical needs for COVID-19 tests across different settings within the UK health and social care sector via an online survey of health and social care professionals and policymakers. Four hundred and forty-seven responses were received between 22nd May and 15th June 2020. Hospitals and care homes were recognized as the settings with the greatest unmet clinical need for COVID-19 diagnostics, despite reporting more access to laboratory molecular testing than other settings. Hospital staff identified a need for diagnostic tests for symptomatic workers and patients. In contrast, care home staff expressed an urgency for screening at the front door to protect high-risk residents and limit transmission. The length of time to test result was considered a widespread problem with current testing across all settings. Rapid tests for staff were regarded as an area of need across general practice and dental settings alongside tests to limit antibiotics use.

Development of a new diagnostic is ideally driven by an understanding of the clinical need that the test addresses and the optimal role the test will have within a care pathway. This survey aimed to understand the clinical need for new sepsis diagnostics and to identify specific clinical scenarios that could be improved by testing. An electronic, cross-sectional survey was circulated to UK National Health Service (NHS) doctors and nurses who care for patients with suspected sepsis in hospitals. Two hundred and sixty-five participants completed the survey, representing 64 NHS Trusts in England. Sixty-seven percent of respondents suggested that the major cause of delay was during the initial identification of sepsis and the subsequent recognition of patients who were deteriorating. Existing blood tests did not enhance the confidence of consultants making their diagnoses. Those surveyed identified a role for a near-patient test to &ldquo, rule out&rdquo, suspected sepsis and, thereby, stop or postpone use of antibiotics. Current diagnostic tests are slow, non-specific, and do not reliably identify patients with a high suspicion of sepsis. As a result, they have a limited use in patient management and antibiotic stewardship. Future development of sepsis diagnostics should focus on overcoming these limitations.

Information about the performance of diagnostic tests is typically presented in the form of measures of test accuracy such as sensitivity and specificity. These measures may be difficult to translate directly into decisions about patient treatment, for which information presented in the form of probabilities of disease after a positive or a negative test result may be more useful. These probabilities depend on the prevalence of the disease, which is likely to vary between populations. This article aims to clarify the relationship between pre-test (prevalence) and post-test probabilities of disease, and presents two free, online interactive tools to illustrate this relationship. These tools allow probabilities of disease to be compared with decision thresholds above and below which different treatment decisions may be indicated. They are intended to help those involved in communicating information about diagnostic test performance and are likely to be of benefit when teaching these concepts. A substantive example is presented using C reactive protein as a diagnostic marker for bacterial infection in the older adult population. The tools may also be useful for manufacturers of clinical tests in planning product development, for authors of test evaluation studies to improve reporting and for users of test evaluations to facilitate interpretation and application of the results.

ObjectiveTo systematically review methods developed and employed to evaluate the diagnostic accuracy of medical test when there is a missing or no gold standard.Study design and settingsArticles that proposed or applied any methods to evaluate the diagnostic accuracy of medical test(s) in the absence of gold standard were reviewed. The protocol for this review was registered in PROSPERO (CRD42018089349).ResultsIdentified methods were classified into four main groups: methods employed when there is a missing gold standard; correction methods (which make adjustment for an imperfect reference standard with known diagnostic accuracy measures); methods employed to evaluate a medical test using multiple imperfect reference standards; and other methods, like agreement studies, and a mixed group of alternative study designs. Fifty-one statistical methods were identified from the review that were developed to evaluate medical test(s) when the true disease status of some participants is unverified with the gold standard. Seven correction methods were identified and four methods were identified to evaluate medical test(s) using multiple imperfect reference standards. Flow-diagrams were developed to guide the selection of appropriate methods.ConclusionVarious methods have been proposed to evaluate medical test(s) in the absence of a gold standard for some or all participants in a diagnostic accuracy study. These methods depend on the availability of the gold standard, its' application to the participants in the study and the availability of alternative reference standard(s). The clinical application of some of these methods, especially methods developed when there is missing gold standard is however limited. This may be due to the complexity of these methods and/or a disconnection between the fields of expertise of those who develop (e.g. mathematicians) and those who employ the methods (e.g. clinical researchers). This review aims to help close this gap with our classification and guidance tools.