Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020.

OBJECTIVE: The aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London. DESIGN: Observational cohort study. SETTING: London North West Healthcare NHS Trust (LNWH). PARTICIPANTS: Patients tested and/or admitted for COVID-19 at LNWH during March and April 2020 MAIN OUTCOME MEASURES: Descriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19. RESULTS: The outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients. CONCLUSION: The findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study.

BACKGROUND: Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35-45%), but no effective pharmacotherapy exists. Production of anti-inflammatory adenosine by ecto-5'-nucleotidase (CD73) helps maintain endothelial barrier function. We tested whether interferon-beta-1a (IFN-beta-1a), which increases CD73 synthesis, can reduce vascular leakage and mortality in patients with ARDS. METHODS: In ex-vivo studies, we first established that IFN-beta-1a induced CD73 up-regulation in cultured human lung tissue samples. We then tested the safety, tolerability, and efficacy of intravenous human recombinant IFN-beta-1a (FP-1201) in patients with ARDS in an open-label study (comprising dose-escalation and expansion phases). We recruited patients from eight intensive care units in the UK. Eligible patients were aged 18 years or older, had ARDS, and were being treated with assisted ventilation. We established an optimal tolerated dose (OTD) in the first, dose-escalation phase. Once established, we gave all subsequently enrolled patients the OTD of intravenous FP-1201 for 6 days. We assessed 28-day mortality (our primary endpoint) in all patients receiving the OTD versus 28-day mortality in a group of patients who did not receive treatment (this control group comprised patients in the study but who did not receive treatment because they were screened during the safety windows after dose escalation). This trial is registered with ClinicalTrials.gov, number NCT00789685, and the EU Clinical Trials Register EudraCT, number 2008-000140-13. FINDINGS: IFN-beta-1a increased the number of CD73-positive vessels in lung culture by four times on day 1 (p=0·04) and by 14·3 times by day 4 (p=0·004). For the clinical trial, between Feb 23, 2009, and April 7, 2011, we identified 150 patients, of whom 37 were enrolled into the trial and given treatment. The control group consisted of 59 patients who were recruited to take part in the study, but who did not receive treatment. Demographic characteristics and severity of illness did not differ between treatment and control groups. The optimal tolerated FP-1201 dose was 10 µg per day for 6 days. By day 28, 3 (8%) of 37 patients in the treatment cohort and 19 (32%) of 59 patients in the control cohort had died-thus, treatment with FP-1201 was associated with an 81% reduction in odds of 28-day mortality (odds ratio 0·19 [95% CI 0·03-0·72]; p=0·01). INTERPRETATION: FP-1201 up-regulates human lung CD73 expression, and is associated with a reduction in 28-day mortality in patients with ARDS. Our findings need to be substantiated in large, prospective randomised trials, but suggest that FP-1201 could be the first effective, mechanistically targeted, disease-specific pharmacotherapy for patients with ARDS.

A multidisciplinary team approach to weaning from prolonged mechanical ventilation.

OBJECTIVE: To establish whether multidisciplinary team-led strategies to maintain continuity across the weaning process result in an increase in the proportion of patients surviving prolonged mechanical ventilation and reduce the length of time patients are ventilated. DESIGN: A quality improvement programme was conceived and implemented for patients receiving mechanical ventilation for >21 days. SETTING: University teaching hospital general intensive care unit. INTERVENTIONS: The introduction of long-term weaning plans. MEASUREMENTS AND MAIN RESULTS: Intensive care unit survival odds ratio and 95% confidence interval. 0.181 (0.06-0.49) P<0.01 and hospital survival odds ratio and 95% confidence interval 0.2 (0.08-0.61) P<0.01, Duration of mechanical ventilation (median 95@ confidence interval ) 53 days (32-37) vs 43 days (39-44) P=0.03. CONCLUSION: Long-term weaning plans led by a multidisciplinary, team were associated with a reduction in intensive care unit and hospital mortality, and duration of mechanical ventilation in patients ventilated for ≥ 21 days. Strategies to maintain continuity in this patient parent group are likely fundamental to improving outcome.

Intraoperative fluid management guided by oesophageal Doppler monitoring.

PROBLEM: Fluid management during major surgery poses a challenge to the surgical team as postoperative complications are often related to giving the wrong amount of intravenous fluid. Postoperative morbidity can be reduced by using the oesophageal Doppler cardiac output monitor to individualise fluid administration, but this technology has not been widely adopted. DESIGN: A campaign for adopting this technology in major surgical specialties explored clinical and managerial barriers throughout the procurement and implementation process. We compared patient outcomes 12 months before implementation and after implementation. SETTING: Three large hospitals in England with different size, geographical location, and case mix. STRATEGIES FOR CHANGE: Project leads at each site included a consultant anaesthetist, a divisional manager, and an audit facilitator. A business case was prepared by each team with support from NHS Technology Adoption Centre, allowing senior management to overcome the unequal spread of costs versus benefits. A survey of anaesthetists revealed concerns about familiarity with the device, which we dealt with by clinicians volunteering to "champion" the technique, supported by standard training provided by the manufacturer. We encouraged appropriate use of the technology by collecting intraoperative patient related data and postoperative patient outcomes and by giving regular, timely feedback. KEY MEASURES FOR IMPROVEMENT: The key outcome measure was length of hospital stay. In-hospital mortality, readmission, and reoperation rates were also recorded. Process measures were use of monitors and change in stroke volume during surgery. EFFECTS OF THE CHANGE: We compared 649 patients after implementation across all sites with 658 matched cases before implementation. Use of Doppler increased from 11% to 65% of eligible operations, with a 3.7 day reduction in total length of stay. Length of stay was reduced at each site, and in most specialties. Concurrent improvements in patient care could have contributed to these findings. The only sign of harm from the intervention was one episode of pulmonary oedema. Mortality, readmission, and reoperation rates all fell non-significantly. LESSONS LEARNT: Managerial barriers consisted of silo budgeting, difficulties with preparing a business case, and fears about uncontrolled implementation. By collecting outcome data, we convinced senior managers to support and sustain investment. Clinical barriers consisted mainly of scepticism regarding clinical effectiveness and worries about training. Clinicians "championing" the technology took on responsibility for data collection, education, advocacy, and spanning boundaries. When barriers to adoption of oesophageal Doppler monitoring are overcome, outcome improvements suggested by research can be replicated in the real world. The project generated a web based guide (www.howtowhyto.nhs.uk) to provide tools and resources to support implementation.