Comparison of COVID-19 survival in relation to CPAP length of treatment and by comorbidity and transmission setting (community or hospital acquired) in a medium-sized UK hospital in 2020: a retrospective study.

OBJECTIVE: To estimate continuous positive airway pressure (CPAP) length of treatment effect on survival of hospitalised COVID-19 patients in a medium-sized UK Hospital, and how this effect changes according to the patient's comorbidity and COVID-19 route of acquisition (community or nosocomial) during the two waves in 2020. SETTING: The acute inpatient unit in Wrightington, Wigan and Leigh Teaching Hospitals National Health Service (NHS) Foundation Trust (WWL), a medium-sized NHS Trust in north-west of England. DESIGN: Retrospective cohort of all confirmed COVID-19 patients admitted in WWL during 2020. PARTICIPANTS: 1830 patients (568 first wave, 1262 s wave) with antigen confirmed COVID-19 disease and severe acute respiratory syndrome admitted between 17 March 2020 (first confirmed COVID-19 case) and 31 December 2020. OUTCOME MEASURE: COVID-19 survival rate in all patients and survival rate in potentially hospital-acquired COVID-19 (PHA) patients were modelled using a predictor set which include comorbidities (eg, obesity, diabetes, chronic ischaemic heart disease (IHD), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD)), wave, age, sex and care home residency, and interventions (remdesivir, dexamethasone, CPAP, intensive care unit (ICU), intubation). Secondary outcome measure was CPAP length, which was modelled using the same predictors of the survival rate. RESULTS: Mortality rate in the second wave was significantly lower than in the first wave (43.4% vs 28.1%, p<0.001), although for PHA COVID-19 patients mortality did not reduce, remaining at very high levels independently of wave and CPAP length. For all cohort, statistical modelling identified CPAP length (HR 95% CI 0.86 to 0.96) and women (HR 95% CI 0.71 to 0.81) were associated with improved survival, while being older age (HR 95% CI 1.02 to 1.03) admitted from care homes (HR 95% CI 2.22 to 2.39), IHD (HR 95% CI 1.13 to 1.24), CKD (HR 95% CI 1.14 to 1.25), obesity (HR 95% CI 1.18 to 1.28) and COPD-emphysema (HR 95% CI 1.18 to 1.57) were associated with reduced survival. Despite the detrimental effect of comorbidities, patients with CKD (95% CI 16% to 30% improvement in survival), IHD (95% CI 1% to 10% improvement in survival) and asthma (95% CI 8% to 30% improvement in survival) benefitted most from CPAP length, while no significant survival difference was found for obese and patients with diabetes. CONCLUSIONS: The experience of an Acute Trust during the COVID-19 outbreak of 2020 is documented and indicates the importance of care home and hospitals in disease acquisition. Death rates fell between the first and second wave only for community-acquired COVID-19 patients. The fall was associated to CPAP length, especially for some comorbidities. While uncovering some risk and protective factors of mortality in COVID-19 studies, the study also unravels how little is known about PHA COVID-19 and the interaction between CPAP and some comorbidities.

CPAP management of COVID-19 respiratory failure: a first quantitative analysis from an inpatient service evaluation.

OBJECTIVE: To evaluate the role of continuous positive air pressure (CPAP) in the management of respiratory failure associated with COVID-19 infection. Early clinical management with limited use of CPAP (3% of patients) was compared with a later clinical management strategy which had a higher proportion of CPAP use (15%). DESIGN: Retrospective case-controlled service evaluation for a single UK National Health Service (NHS) Trust during March-June 2020 designed and conducted solely to estimate the effects of current care. SETTING: The acute inpatient unit in Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust, a medium-sized English NHS Trust. PARTICIPANTS: 206 patients with antigen confirmed COVID-19 disease and severe acute respiratory syndrome admitted between 17 March 2020 and 3 April 2020 for the early group (controls), and between 10 April 2020 and 11 May 2020 for the late group (cases). Follow-up for all cases was until 11 June by which time all patients had a final outcome of death or discharge. Both groups were composed of 103 patients. Cases and controls were matched by age and sex. OUTCOME MEASURE: The outcome measure was the proportion of patients surviving at time t (time from the positive result of COVID-19 test to discharge/death date). The predictors were CPAP intervention, intubation, residence in care homes and comorbidities (renal, pulmonary, cardiac, hypertension and diabetes). A stratified Cox proportional hazard for clustered data (via generalised estimating equations) and model selection algorithms were employed to identify the effect of CPAP on patients' survival and the effect on gas exchange as measured by alveolar arterial (A-a) gradient and timing of CPAP treatment on CPAP patients' survival. RESULTS: CPAP was found to be significantly (HR 0.38, 95% CI 0.36 to 0.40) associated with lower risk of death in patients with hospital stay equal to, or below 7 days. However, for longer hospitalisation CPAP was found to be associated with increased risk of death (HR 1.72, 95% CI 1.40 to 2.12). When CPAP was initiated within 4 days of hospital admission, the survival probability was above 73% (95% CI 53% to 99%). In addition, lower A-a gradient was associated with lower risk of death in CPAP patients (HR 1.011, 95% CI 1.010 to 1.013). The selected model (best fit) was stratified by sex and clustered by case/control groups. The predictors were age, intubation, hypertension and the residency from care homes, which were found to be statistically significantly associated with patient's death/discharge. CONCLUSIONS: CPAP is a simple and cost-effective intervention. It has been established for care of other respiratory disorders but not for COVID-19 respiratory failure. This evaluation establishes that CPAP as a potentially viable treatment option for this group of patients during the first days of hospital admission. As yet there is limited availability of quantitative research on CPAP use for COVID-19. Whist this work is hampered by both the relatively small sample size and retrospective design (which reduced the ability to control potential confounders), it represents evidence of the significant benefit of early CPAP intervention. This evaluation should stimulate further research questions and larger study designs on the potential benefit of CPAP for COVID-19 infections. Globally, this potentially beneficial low cost and low intensity therapy could have added significance economically for healthcare provision in less developed countries.

Extensive diversification is a common feature of Pseudomonas aeruginosa populations during respiratory infections in cystic fibrosis.

BACKGROUND: Populations of the Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa undergo extensive diversification in the cystic fibrosis (CF) lung during long-term chronic infections. METHODS: We analyzed sets of 40 isolates from the sputa of five CF patients, each chronically infected with a different non-LES strain of P. aeruginosa. For each sample (two per patient), diversity was assessed by characterizing nine phenotypic traits. RESULTS: All P. aeruginosa populations were highly diverse, with the majority of phenotypic variation being due to within-sample diversity. CONCLUSIONS: Maintenance of diverse populations in the CF lung is a common feature of P. aeruginosa infections.

Halting the spread of epidemic pseudomonas aeruginosa in an adult cystic fibrosis centre: a prospective cohort study.

OBJECTIVES: To assess if cohort segregation policies are effective in preventing cross-infection in cystic fibrosis (CF) clinics. DESIGN: A prospective cohort study. SETTING: A large adult CF centre in Northwest England. PARTICIPANTS: All CF patients cared for at the Liverpool adult CF centre 2003-2009. METHODS: Regular sputum sampling with genotyping of pseudomonas aeruginosa (Psa) isolates led to a policy of inpatient and outpatient segregation by microbiological group. MAIN OUTCOME MEASURES: Prevalence and cross-infection/super-infection rates of a transmissible Psa strain, i.e. the Liverpool epidemic strain (LES) in adult CF patients at the Liverpool adult CF centre from 2003 to 2009. RESULTS: There was a decline in the proportion of patients with LES (71-53%) and an increase in those with unique strains (23-31%) and without Psa infection (6-17%) from 2003 to 2009. There were two cases of LES super-infection and one case of new chronic Psa infection (with a unique strain). There were no cases of transmissible strain infection in patients previously uninfected by Psa. CONCLUSIONS: Our segregation policy has halted the spread of the commonest highly transmissible strain in the UK (LES) in our clinic, without endangering patients who were not previously infected with Psa. It confirms that if genotypic surveillance is used, it is unnecessary to segregate patients infected with unique strains from those without Psa infection.

Health-related quality of life in Cystic Fibrosis patients infected with transmissible Pseudomonas aeruginosa strains: cohort study.

OBJECTIVES: To assess the impact on health-related quality of life (HRQoL) in adult cystic fibrosis (CF) patients of chronic infection with the Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa (Psa). DESIGN: Cohort study. PARTICIPANTS: Adult CF patients attending a single CF centre. SETTING: Outpatient clinic. MAIN OUTCOME MEASURES: HRQoL measures of adult CF patients chronically infected with LES and Psa strains measured by CFQ-UK. RESULTS: Patients infected by transmissible Psa strains had worse physical functioning, respiratory symptoms, treatment burden, vitality, role, health perception and emotion than those with unique Psa strains (P < 0.01), and significantly poorer physical functioning, respiratory symptoms, treatment burden, body image, weight, role, and emotion than those without any Psa infection (P < 0.05). Furthermore, in a matched cohort of 39 patients, those with LES infection reported significantly worse physical functioning, treatment burden, respiratory symptoms and health perception than those with unique Psa infection (P < 0.02). CONCLUSION: Chronic infection with transmissible Psa strains, particularly LES, confers a worse quality of life in adult CF patients. Coupled with the established poorer clinical outcome, this reinforces the need to prevent the spread of such strains in CF community.

Increasing resistance of the Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa (Psa) to antibiotics in cystic fibrosis (CF)--a cause for concern?

BACKGROUND: Transmissible Pseudomonas aeruginosa (Psa) strains such as the Liverpool Epidemic Strain (LES) are now widespread throughout UK CF clinics: their susceptibility to antibiotics is therefore important. To study this, we compared antibiogram patterns of Psa strains in our CF clinic over 5 years, looking at differences in resistance patterns between strains and changes to these over time. METHODS: The antibiograms of sputum samples between 2004 and 2008 from patients attending our centre were included. We compared Psa isolate antibiotic resistance (to six anti-pseudomonal antibiotics) patterns for patients infected with LES with those infected with other Psa strains, both in the total population in 2004 (125 patients) and 2008 (166 patients) and also longitudinally from annual review samples 2004 to 2008 in matched and unmatched patient groups. RESULTS: LES exhibited significantly more resistant isolates in 2004 (p<0.0001). There was an increase in antibiotic resistance in both LES and other Psa strains over time (p<0.001). Cox proportional hazards analysis of both unmatched (n=125) and matched (n=56) patients in 2004 revealed that LES infected patients were more likely to develop antibiotic resistant isolates over time (hazard ratio 8.1, p<0.001). Fewer LES isolates were classed as fully sensitive in both matched and unmatched groups at the end of study period (p<0.001). CONCLUSION: This study shows a worrying trend in antibiotic resistance in the Psa isolates amongst patients chronically infected with LES. This highlights the need to prevent cross infection through segregation and also the need to develop new strategies to treat these organisms.