Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO).

BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Correction: Expanding the utility of the ROX index among patients with acute hypoxemic respiratory failure.

[This corrects the article DOI: 10.1371/journal.pone.0261234.].

Nutrition support practices for critically ill patients with severe acute respiratory syndrome coronavirus-2: A multicentre observational study in Singapore.

INTRODUCTION: To improve the nutritional care and resource allocation of critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), we described their characteristics, treatment modalities and clinical outcomes, and compared their nutrition interventions against the American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations. METHODS: This was a retrospective observational study conducted in 5 tertiary hospitals in Singapore. Characteristics, treatment modalities, clinical outcomes and nutrition interventions of critically ill patients with SARS-CoV-2 who received enteral and parenteral nutrition were collected between January and May 2020. RESULTS: Among the 83 critically ill patients with SARS-CoV-2, 22 (28%) were obese, 45 (54%) had hypertension, and 21 (25%) had diabetes. Neuromuscular blockade, prone therapy and dialysis were applied in 70% (58), 47% (39) and 35% (29) of the patients, respectively. Refeeding hypophosphataemia and hospital mortality occurred respectively in 6% (5) and 18% (15) of the critically ill patients with SARS-CoV-2. Late enteral nutrition and cardiovascular comorbidities were associated with higher hospital mortality (adjusted relative risk 9.00, 95% confidence interval [CI] 2.25-35.99; 6.30, 95% CI 1.15-34.40, respectively). Prone therapy was not associated with a higher incidence of high gastric residual volume (≥250mL). The minimum caloric (15kcal/kg) and protein (1.2g/kg) recommendations of ASPEN were achieved in 54% (39) and 0% of the patients, respectively. CONCLUSION: The high obesity prevalence and frequent usage of neuromuscular blockade, prone therapy, and dialysis had considerable implications for the nutritional care of critically ill patients with SARS-CoV-2. They also did not receive adequate calories and protein. More audits should be conducted to refine nutritional interventions and guidelines for this ever-evolving disease.

Sepsis, cardiovascular events and short-term mortality risk in critically ill patients.

INTRODUCTION: There is paucity of data on the occurrence of cardiovascular events (CVEs) in critically ill patients with sepsis. We aimed to describe the incidence, risk factors and impact on mortality of CVEs in these patients. METHODS: This was a retrospective cohort study of critically ill patients admitted to the medical intensive care unit (ICU) between July 2015 and October 2016. The primary outcome was intra-hospital CVEs, while the secondary outcomes were in-hospital mortality, ICU and hospital length of stay. RESULTS: Patients with sepsis (n=662) had significantly more CVEs compared to those without (52.9% versus 23.0%, P<0.001). Among sepsis patients, 350 (52.9%) had 1 or more CVEs: 59 (8.9%) acute coronary syndrome; 198 (29.9%) type 2 myocardial infarction; 124 (18.7%) incident atrial fibrillation; 76 (11.5%) new or worsening heart failure; 32 (4.8%) cerebrovascular accident; and 33 (5.0%) cardiovascular death. Factors associated with an increased risk of CVEs (adjusted relative risk [95% confidence interval]) included age (1.013 [1.007-1.019]); ethnicity-Malay (1.214 [1.005-1.465]) and Indian (1.240 [1.030-1.494]) when compared to Chinese; and comorbidity of ischaemic heart disease (1.317 [1.137-1.527]). There were 278 patients (79.4%) who developed CVEs within the first week of hospitalisation. Sepsis patients with CVEs had a longer median (interquartile range [IQR]) length of stay in the ICU (6 [3-12] vs 4 [2-9] days, P<0.001), and hospital (21 [10-42] vs 15 [7-30] days, P<0.001) compared to sepsis patients without CVEs. There was no difference in in-hospital mortality between the 2 groups (46.9% vs 45.8%, P=0.792). CONCLUSION: CVEs complicate half of the critically ill patients with sepsis, with 79.4% of patients developing CVEs within the first week of hospitalisation, resulting in longer ICU and hospital length of stay.

Mobile device: a useful tool to teach inhaler devices to healthcare professionals.

BACKGROUND: Proper inhaler device usage is paramount for control of underlying obstructive airway disease. Hence, education to healthcare professionals who will eventually educate patients need to be done effectively. We developed an application for mobile devices for education on six medical inhaler devices, the metered-dose inhaler (MDI), Turbuhaler, Accuhaler, Breezhaler, Ellipta and Respimat, and studied if there were any difference between the application and the manufacturer's instructions on inhaler technique. The aim of this study is to see if inhaler education via a mobile phone app is comparable to manual instruction for health care professions. METHODS: Participants, who were nursing students, were randomized to learn the inhaler devices via the manufacturer's instruction guide or a mobile device app designed specifically for education on inhaler devices. RESULTS: There were 45 participants in each group. 78% of them were females with a median age of 21 (IQR 3). 67% used an Apple mobile device and the remainder used an Android device. The mobile device showed better total improvement points for the Turbuhaler device (262 vs 287 points; P = 0.02). Participants learning from the manufacturer's guide had a significantly higher total improvement points in the Breezhaler (370 vs 327 points; P < 0.01) and Ellipta (214 vs 174 points; P < 0.01) device. Both interventions showed improvement in total scores for demonstrating the correct usage of all inhaler devices. MDI has the least number of correct steps for both interventions. The participants' reported their mean (SD) self-rated knowledge was significantly higher for those using the app for all devices as compared to those that did not (4.33 (0.68) vs 4.73 (0.42); P = < 0.01). Self-reported confidence level was found to be higher in the mobile app group, but this was not statistically significant. The app was well received and scored of 4.42 of 5 with regards to its quality. CONCLUSION: Using a mobile inhaler app is just as effective to teach inhaler device techniques to healthcare professionals and is likely a more convenient, versatile and important adjunct to learning. TRIAL REGISTRATION: National Healthcare Group Ethics Board (2018/00960).

Expanding the utility of the ROX index among patients with acute hypoxemic respiratory failure.

BACKGROUND: Delaying intubation in patients who fail high-flow nasal cannula (HFNC) may result in increased mortality. The ROX index has been validated to predict HFNC failure among pneumonia patients with acute hypoxemic respiratory failure (AHRF), but little information is available for non-pneumonia causes. In this study, we validate the ROX index among AHRF patients due to both pneumonia or non-pneumonia causes, focusing on early prediction. METHODS: This was a retrospective observational study in eight Singapore intensive care units from 1 January 2015 to 30 September 2017. All patients >18 years who were treated with HFNC for AHRF were eligible and recruited. Clinical parameters and arterial blood gas values at HFNC initiation and one hour were recorded. HFNC failure was defined as requiring intubation post-HFNC initiation. RESULTS: HFNC was used in 483 patients with 185 (38.3%) failing HFNC. Among pneumonia patients, the ROX index was most discriminatory in pneumonia patients one hour after HFNC initiation [AUC 0.71 (95% CI 0.64-0.79)], with a threshold value of <6.06 at one hour predicting HFNC failure (sensitivity 51%, specificity 80%, positive predictive value 61%, negative predictive value 73%). The discriminatory power remained moderate among pneumonia patients upon HFNC initiation [AUC 0.65 (95% CI 0.57-0.72)], non-pneumonia patients at HFNC initiation [AUC 0.62 (95% CI 0.55-0.69)] and one hour later [AUC 0.63 (95% CI 0.56-0.70)]. CONCLUSION: The ROX index demonstrated moderate discriminatory power among patients with either pneumonia or non-pneumonia-related AHRF at HFNC initiation and one hour later.

High-flow nasal cannula therapy: A multicentred survey of the practices among physicians and respiratory therapists in Singapore.

BACKGROUND: Use of high-flow nasal cannula (HFNC) has become a regular intervention in the intensive care units especially in patients coming in with hypoxaemic respiratory failure. Clinical practices may differ from published literature. OBJECTIVES: The objective of this study was to determine the clinical practices of physicians and respiratory therapists (RTs) on the use of HFNC. METHODS: A retrospective observational study looking at medical records on HFNC usage from January 2015 to September 2017 was performed and was followed by a series of questions related to HFNC practices. The survey involved physicians and RTs in intensive care units from multiple centres in Singapore from January to April 2018. Indications and thresholds for HFNC usage with titration and weaning practices were compared with the retrospective observational study data. RESULTS: One hundred twenty-three recipients (69.9%) responded to the survey and reported postextubation (87.8%), pneumonia in nonimmunocompromised (65.9%), and pneumonia in immunocompromised (61.8%) patients as the top three indications for HFNC. Of all, 39.8% of respondents wanted to use HFNC for palliative intent. Similar practices were observed in the retrospective study with the large cohort of 63% patients (483 of the total 768 patients) where HFNC was used for acute hypoxaemic respiratory failure and 274 (35.7%) patients to facilitate extubation. The survey suggested that respondents would initiate HFNC at a lower fraction of inspired oxygen (FiO2), higher partial pressure of oxygen to FiO2 ratio, and higher oxygen saturation to FiO2 ratio for nonpneumonia patients than patients with pneumonia. RTs were less likely to start HFNC for patients suffering from pneumonia and interstitial lung disease than physicians. RTs also preferred adjustment of FiO2 to improve oxygen saturations and noninvasive ventilation for rescue. CONCLUSIONS: Among the different intensive care units surveyed, the indications and thresholds for the initiation of HFNC differed in the clinical practices of physicians and RTs.

Association between lung compliance phenotypes and mortality in COVID-19 patients with acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with a high mortality rate, though outcomes of the different lung compliance phenotypes are unclear. We aimed to measure lung compliance and examine other factors associated with mortality in COVID-19 patients with ARDS. METHODS: Adult patients with COVID-19 ARDS who required invasive mechanical ventilation at 8 hospitals in Singapore were prospectively enrolled. Factors associated with both mortality and differences between high (<40mL/cm H2O) and low (<40mL/cm H2O) compliance were analysed. RESULTS: A total of 102 patients with COVID-19 who required invasive mechanical ventilation were analysed; 15 (14.7%) did not survive. Non-survivors were older (median 70 years, interquartile range [IQR] 67-75 versus median 61 years, IQR 52-66; P<0.01), and required a longer duration of ventilation (26 days, IQR 12-27 vs 8 days, IQR 5-15; P<0.01) and intensive care unit support (26 days, IQR 11-30 vs 11.5 days, IQR 7-17.3; P=0.01), with a higher incidence of acute kidney injury (15 patients [100%] vs 40 patients [46%]; P<0.01). There were 67 patients who had lung compliance data; 24 (35.8%) were classified as having high compliance and 43 (64.2%) as having low compliance. Mortality was higher in patients with high compliance (33.3% vs 11.6%; P=0.03), and was associated with a drop in compliance at day 7 (-9.3mL/cm H2O (IQR -4.5 to -15.4) vs 0.2mL/cm H2O (4.7 to -5.2) P=0.04). CONCLUSION: COVID-19 ARDS patients with higher compliance on the day of intubation and a longitudinal decrease over time had a higher risk of death.

Nosocomial infections among COVID-19 patients: an analysis of intensive care unit surveillance data.

Surveillance of nosocomial infections, like catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection, possible ventilator-associated pneumonia and secondary bloodstream infections were observed to study the impact of COVID-19 outbreak in ICUs from Tan Tock Seng Hospital and National Centre for Infectious Diseases, Singapore between February and June 2020. Higher nosocomial infection rates were observed in COVID-19 patients, although it was not statistically significant. Moreover, COVID-19 patients seem to be more predisposed to CAUTI despite a higher proportion of non-COVID-19 patients having urinary catheters. Thus, continued vigilance to ensure adherence to IPC measures is needed.

Predictors and outcomes of high-flow nasal cannula failure following extubation: A multicentre observational study.

INTRODUCTION: Despite adhering to criteria for extubation, up to 20% of intensive care patients require re-intubation, even with use of post-extubation high-flow nasal cannula (HFNC). This study aims to identify independent predictors and outcomes of extubation failure in patients who failed post-extubation HFNC. METHODS: We conducted a multicentre observational study involving 9 adult intensive care units (ICUs) across 5 public hospitals in Singapore. We included patients extubated to HFNC following spontaneous breathing trials. We compared patients who were successfully weaned off HFNC with those who failed HFNC (defined as re-intubation ≤7 days following extubation). Generalised additive logistic regression analysis was used to identify independent risk factors for failed HFNC. RESULTS: Among 244 patients (mean age: 63.92±15.51 years, 65.2% male, median APACHE II score 23.55±7.35), 41 (16.8%) failed HFNC; hypoxia, hypercapnia and excessive secretions were primary reasons. Stroke was an independent predictor of HFNC failure (odds ratio 2.48, 95% confidence interval 1.83-3.37). Failed HFNC, as compared to successful HFNC, was associated with increased median ICU length of stay (14 versus 7 days, P<0.001), ICU mortality (14.6% versus 2.0%, P<0.001) and hospital mortality (29.3% versus 12.3%, P=0.006). CONCLUSION: Post-extubation HFNC failure, especially in patients with stroke as a comorbidity, remains a clinical challenge and predicts poorer clinical outcomes. Our observational study highlights the need for future prospective trials to better identify patients at high risk of post-extubation HFNC failure.

Clinical features and predictors of severity in COVID-19 patients with critical illness in Singapore.

We aim to describe a case series of critically and non-critically ill COVID-19 patients in Singapore. This was a multicentered prospective study with clinical and laboratory details. Details for fifty uncomplicated COVID-19 patients and ten who required mechanical ventilation were collected. We compared clinical features between the groups, assessed predictors of intubation, and described ventilatory management in ICU patients. Ventilated patients were significantly older, reported more dyspnea, had elevated C-reactive protein and lactate dehydrogenase. A multivariable logistic regression model identified respiratory rate (aOR 2.83, 95% CI 1.24-6.47) and neutrophil count (aOR 2.39, 95% CI 1.34-4.26) on admission as independent predictors of intubation with area under receiver operating characteristic curve of 0.928 (95% CI 0.828-0.979). Median APACHE II score was 19 (IQR 17-22) and PaO2/FiO2 ratio before intubation was 104 (IQR 89-129). Median peak FiO2 was 0.75 (IQR 0.6-1.0), positive end-expiratory pressure 12 (IQR 10-14) and plateau pressure 22 (IQR 18-26) in the first 24 h of ventilation. Median duration of ventilation was 6.5 days (IQR 5.5-13). There were no fatalities. Most COVID-19 patients in Singapore who required mechanical ventilation because of ARDS were extubated with no mortality.

Coronavirus Disease 2019 (COVID-19): The Singapore Experience. A Review of the First Eight Months.

As of 27 October 2020, there have been 57,980 confirmed cases of COVID-19 in Singapore, with 28 fatalities. To summarise the Singapore experience in managing and containing COVID-19 based on available published data and from relevant sources, a review of literature using research databases such as PubMed and OVID Medline, along with non-peer-reviewed articles and other sources, was conducted with the search terms 'COVID-19' and 'Singapore'. Research conducted in Singapore has provided insight into the clinical manifestations and period of infectivity of COVID-19, demonstrated evidence of pre-symptomatic transmission, linked infection clusters using serological tools, and highlighted aspects of hospital-based environmental contamination. It has also provided guidance for diagnostic testing and has described immune and virologic correlates with disease severity. Evidence of effectiveness of containment measures such as early border control, rigorous contact training, and calibrated social distancing measures have also been demonstrated. Singapore's multipronged strategy has been largely successful at containing COVID-19 and minimising fatalities, but the risk of re-emergence is high.

Perceived Stress, Stigma, Traumatic Stress Levels and Coping Responses amongst Residents in Training across Multiple Specialties during COVID-19 Pandemic-A Longitudinal Study.

This study aimed to explore changes in psychological responses (perceived stress, traumatic stress, stigma, coping) over time in residents, as well as their predictors. The level of perceived stress, traumatic stress, stigma, and coping responses were assessed using the Perceived Stress Scale, Impact of Event-Revised, Healthcare Workers Stigma Scale, and Brief Coping Orientation to Problems Experienced (COPE) Inventory, respectively. We collected responses from 274 residents at baseline and 221 residents at 3 months follow-up (timepoint 2) from the National Healthcare Group (NHG) residency programs in Singapore. All residents reported lower perceived stress and lower perceived stigma compared to baseline. Use of avoidance coping was associated with all three psychological responses (perceived stress, traumatic stress, and stigma) across the two timepoints. Compared to baseline, specific factors associated with perceived stress and traumatic stress at timepoint 2 were living alone, less problem solving, and seeking social support. Residency programs should encourage active coping strategies (e.g., seeking social support, positive thinking, problem solving) among residents, and proactively identify residents who may be at higher risk of psychological sequelae due to circumstances that contribute to isolation.

Clinical course and physiotherapy intervention in 9 patients with COVID-19.

Since the outbreak of the 2019 novel coronavirus (COVID-19), the role of physiotherapy for patients with COVID-19 infection has been highlighted by various international guidelines. Despite that, clinical information regarding the rehabilitation of patients with COVID-19 infection remains limited. In this case series, we provide a novel insight into the physiotherapy management in patients infected with COVID-19 in Singapore. The main findings are: (1) Respiratory physiotherapy interventions were not indicated in the majority of the patients with COVID-19 in this case series; (2) During rehabilitation, exertional or position-related desaturation is a common feature observed in critically ill patients with COVID-19 infection locally. This clinical phenomenon of exertional or positional-related desaturation has significantly slowed down the progression of rehabilitation in our patients. As such, it can potentially result in a significant burden on healthcare resources to provide rehabilitation to these patients. Based on these findings, we have highlighted several recommendations for the provision of rehabilitation in patients who are critically ill with COVID-19.

Reversible platypnea-orthodeoxia in COVID-19 acute respiratory distress syndrome survivors.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical syndrome characterized by orthostatic oxygen desaturation and positional dyspnea from supine to an upright position. We observed POS in 5 of 20 cases of severe 2019 novel coronavirus (COVID-19) pneumonia, which demonstrated persistently elevated shunt fraction even after liberation from mechanical ventilation. POS was first observed during physiotherapy sessions; median oxygen desaturation was 8 % (range: 8-12 %). Affected individuals were older (median 64 vs 53 years old, p = 0.05) and had lower body mass index (median 24.7 vs 27.6 kg/m2, p = 0.03) compared to those without POS. While POS caused alarm and reduced tolerance to therapy, this phenomenon resolved over a median of 17 days with improvement of parenchymal disease. The mechanisms of POS are likely due to gravitational redistribution of pulmonary blood flow resulting in increased basal physiological shunting and upper zone dead space ventilation due to the predominantly basal distribution of consolidative change and reported vasculoplegia and microthrombi in severe COVID-19 disease.

Acute Functional Outcomes in Critically Ill COVID-19 Patients.

Background: COVID-19 (Coronavirus Disease 2019) is a global cause of morbidity and mortality currently. We aim to describe the acute functional outcomes of critically ill coronavirus disease 2019 (COVID-19) patients after transferring out of the intensive care unit (ICU). Methods: 51 consecutive critically ill COVID-19 patients at a national designated center for COVID-19 were included in this exploratory, retrospective observational cohort study from January 1 to May 31, 2020. Demographic and clinical data were collected and analyzed. Functional outcomes were measured primarily with the Functional Ambulation Category (FAC), and divided into 2 categories: dependent ambulators (FAC 0-3) and independent ambulators (FAC 4-5). Multivariate analysis was performed to determine associations. Results: Many patients were dependent ambulators (47.1%) upon transferring out of ICU, although 92.2% regained independent ambulation at discharge. On multivariate analysis, we found that a Charlson Comorbidity Index of 1 or more (odds ratio 14.02, 95% CI 1.15-171.28, P = 0.039) and a longer length of ICU stay (odds ratio 1.50, 95% CI 1.04-2.16, P = 0.029) were associated with dependent ambulation upon discharge from ICU. Conclusions: Critically ill COVID-19 survivors have a high level of impairment following discharge from ICU. Such patients should be screened for impairment and managed appropriately by rehabilitation professionals, so as to achieve good functional outcomes on discharge.