Point of care testing of Influenza A/B and RSV in an adult respiratory assessment unit is associated with improvement in isolation practices and reduction in hospital length of stay.

Introduction. Every winter seasonal influenza and other viral respiratory infections increase pressure on the health services and are associated with nosocomial infection and morbidity.Aim. To compare provision of point-of-care (POC) testing with laboratory-based testing for influenza and RSV detection on an adult respiratory assessment unit to assess the impact on isolation practices and length of stay (LOS).Methodology. Prospective interrupted 'on-off' study in adults admitted to the respiratory unit between December 2018 and April 2019 with a suspected respiratory tract infection. Nasopharyngeal samples were tested using either the GeneXpert rapid POC test for influenza and RSV (on-period), or were sent to the laboratory for multiplex PCR testing against a panel of 12 respiratory viruses (off-period). Outcome measures were time to patient isolation for infection control, LOS and turnaround time from admission to test results.Results. Of 1145 patients evaluated, 755 were tested with POC and 390 with laboratory multiplex; a respiratory virus was identified in 164 (21.7 %) and 138 (35.4 %) patients respectively. A positive POC test was associated with a shorter time to isolation (mean difference 16.9 h, P<0.001), shorter LOS (mean difference 15.5 h, P=0.05,) and shorter turnaround time (mean difference 28.3 h, P<0.001), compared to laboratory testing.Conclusion. Use of GeneXpert POC testing for Flu/RSV is associated with rapid reporting of results with significant improvements in isolation practices and reductions in LOS.

Healthcare reconsultation in working-age adults following hospitalisation for community-acquired pneumonia.

Community-acquired pneumonia (CAP) is associated with prolonged symptom persistence during recovery. However, the effect of the residual symptom load on healthcare utilisation is unknown. The aim of this study was to quantify healthcare reconsultation within 28 days of hospital discharge for an index episode of CAP, and explore reasons for these reconsultations. Adults of working age admitted to any of four hospitals in the UK, with a primary diagnosis of CAP, were prospectively studied. Of 108 patients, 71 (65.7%) reconsulted healthcare services within 28 days of discharge; of these, 90.1% consulted their GP. Men were less likely to reconsult than women (adjusted odds ratio [aOR] 0.34, 95% confidence interval 0.13-0.91, p=0.032). Persistence of respiratory symptoms accounted for the majority of these reconsultations. Healthcare utilisation is high in working-age adults after an episode of hospitalised CAP and, in most cases, is due to failure to resolve index symptoms.

Improving readiness for recruitment through simulated trial activation: the Adjuvant Steroids in Adults with Pandemic influenza (ASAP) trial.

BACKGROUND: Research in public health emergencies requires trials to be set up in readiness for activation at short notice and in anticipation of limited timelines for patient recruitment. We conducted a simulated activation of a hibernating pandemic influenza clinical trial in order to test trial processes and to determine the value of such simulation in maintaining trial readiness. METHODS: The simulation involved the Nottingham Clinical Trials Unit, one participating hospital, one manufacturing unit and the Investigational Medicinal Product (IMP) supplier. During the exercise, from 15 September 2015 to 2 December 2015, clinical staff at the participating site completed the trial training package, a volunteer acting as a patient was recruited to the study, 'dummy' IMP was prescribed and follow-up completed. RESULTS: Successful activation of the hibernating trial with patient recruitment within 4 weeks of 'arousal' as planned was demonstrated. A need for greater resilience in anticipation of staff absenteeism was identified, particularly in relation to key trial procedures where the potential for delay is high. A specific issue relating to the IMP Stock Control System was highlighted as a potential source of error that could compromise the randomisation sequence. The simulation exercise was well received by site investigators and increased their confidence in being able to meet the likely demands of the trial when activated. The estimated cost of the exercise was £1995; 90% of this being staff costs. CONCLUSIONS: Simulated activation is useful as a means to test, and prepare for, the rapid activation of 'hibernating' research studies. Whether simulation exercises can also help reduce waste in complex clinical trial research deserves further exploration. TRIAL REGISTRATION: EudraCT Number 2013-001051-12, ISRCTN72331452 . Registered on 6 March 2013.

Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial 'in hibernation', ready for rapid activation.

BACKGROUND: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias. OBJECTIVES: To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic. DESIGN: Multicentre, pragmatic, blinded, randomised placebo-controlled trial. SETTING: Thirty to 40 hospitals in the UK. PARTICIPANTS: Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic. INTERVENTION: Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission. MAIN OUTCOME MEASURE: Admission to Intensive Care Unit, or death, within 30 days of admission to hospital. RESULTS: This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified. CONCLUSIONS: This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.

An evaluation of community assessment tools (CATs) in predicting use of clinical interventions and severe outcomes during the A(H1N1)pdm09 pandemic.

During severe influenza pandemics healthcare demand can exceed clinical capacity to provide normal standards of care. Community Assessment Tools (CATs) could provide a framework for triage decisions for hospital referral and admission. CATs have been developed based on evidence that supports the recognition of severe influenza and pneumonia in the community (including resource limited settings) for adults, children and infants, and serious feverish illness in children. CATs use six objective criteria and one subjective criterion, any one or more of which should prompt urgent referral and admission to hospital. A retrospective evaluation of the ability of CATs to predict use of hospital-based interventions and patient outcomes in a pandemic was made using the first recorded routine clinical assessment on or shortly after admission from 1520 unselected patients (800 female, 480 children <16 years) admitted with PCR confirmed A(H1N1)pdm09 infection (the FLU-CIN cohort). Outcome measures included: any use of supplemental oxygen; mechanical ventilation; intravenous antibiotics; length of stay; intensive or high dependency care; death; and "severe outcome" (combined: use of intensive or high dependency care or death during admission). Unadjusted and multivariable analyses were conducted for children (age <16 years) and adults. Each CATs criterion independently identified both use of clinical interventions that would in normal circumstances only be provided in hospital and patient outcome measures. "Peripheral oxygen saturation ≤ 92% breathing air, or being on oxygen" performed well in predicting use of resources and outcomes for both adults and children; supporting routine measurement of peripheral oxygen saturation when assessing severity of disease. In multivariable analyses the single subjective criterion in CATs "other cause for clinical concern" independently predicted death in children and in adults predicted length of stay, mechanical ventilation and "severe outcome"; supporting the role of clinical acumen as an important independent predictor of serious illness.

CURB-65 pneumonia severity assessment adapted for electronic decision support.

BACKGROUND: Accurate severity assessment is crucial to the initial management of community-acquired pneumonia (CAP). The CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) score contains data that are entered routinely in electronic medical records and are, thus, electronically calculable. The aim of this study was to determine whether an electronically generated severity estimate using CURB-65 elements as continuous and weighted variables better predicts 30-day mortality than the traditional CURB-65. METHODS: In a retrospective cohort study at a US university-affiliated community teaching hospital, we identified 2,069 patients aged 18 years or older with CAP confirmed by radiographic findings in the ED. CURB-65 elements were extracted from the electronic medical record, and 30-day mortality was identified with the Utah Population Database. Performance of a severity prediction model using continuous and weighted CURB-65 variables was compared with the traditional CURB-65 in the US derivation population and validated in the original 1,048 patients from the CURB-65 international derivation study. RESULTS: The traditional, binary CURB-65 score predicted mortality in the US cohort with an area under the curve (AUC) of 0.82. Our severity prediction model generated from continuous, weighted CURB-65 elements was superior to the traditional CURB-65, with an out-of-bag AUC of 0.86 (P < .001). This finding was validated in the international database, with an AUC of 0.85 for the electronic model compared with 0.80 for the traditional CURB-65 (P = .01). CONCLUSIONS: Using CURB-65 elements as continuous and weighted data improved prediction of 30-day mortality and could be used as a real-time, electronic decision support tool or to adjust outcomes by severity when comparing processes of care.

What is the role of pulse oximetry in the assessment of patients with community-acquired pneumonia in primary care?

INTRODUCTION: Community-acquired pneumonia (CAP) is a common presenting condition in primary care. Assessment of oxygenation status using pulse oximetry is increasingly available, but its precise role in disease severity assessment is unknown. AIMS: To inform the use of pulse oximetry in patients with CAP, including the utility of different oxygenation thresholds, patient subgroups, and interaction with existing severity scores. METHODS: A prospective cohort study of adults with CAP admitted to a UK teaching hospital trust. Oxygen saturations (SpO2) and the fraction of inspired oxygen were recorded on admission. The value of different SpO2 thresholds (< 88%, ≤ 90%, ≤ 92%, and < 95%) in predicting 30-day mortality and critical care admission was analysed. RESULTS: 467 patients had SpO2 measured on room air. Admission SpO2 ≤ 90% was observed in 28% of patients and had reasonable specificity (76%) for 30-day mortality or critical care admission, but low sensitivity (46%). Specificity was particularly good for adults <50 years of age (90%) or those with asthma (92.3%). CONCLUSION: SpO2 ≤ 90% has good specificity but low sensitivity for adverse outcomes in CAP. It complements rather than replaces clinical severity scoring.

Importance of severity of illness assessment in management of lower respiratory infections.

PURPOSE OF REVIEW: Patients with lower respiratory infections display a wide spectrum of disease severity. Management decisions regarding site of care, extent of investigations and level of treatment are mainly based on disease severity. Several severity assessment tools are still undergoing evaluation. This review highlights recent relevant studies. RECENT FINDINGS: Severity prediction rules such as the Pneumonia Severity Index cannot be relied upon as the sole means of identifying patients with lower respiratory infections who do not need hospital admission. Up to 40% of patients assigned to low-risk groups may require hospitalization. The most common medical reason for hospitalization in these circumstances is the presence of unstable comorbid illness. Social factors are equally important in the decision to admit. A new prediction rule based on the British Thoracic Society prediction rule has been proposed. This divides patients with community acquired pneumonia into three management groups based on risk of mortality. A prediction rule for use in patients with HIV-associated community acquired pneumonia has also been proposed. An IL-10 polymorphism has been identified as a prognostic factor in community acquired pneumonia. Audits examining the impact of adherence to severity-based guidelines on the outcome of community acquired pneumonia have revealed conflicting results. Differences in outcome may only be significant for patients with the most severe illness. SUMMARY: Severity of illness assessment is important in guiding management options at various stages in the clinical course of lower respiratory infections. However, no prediction rule should supercede clinical judgment.