Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC).

Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.

Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. METHODS: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. RESULTS: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis. CONCLUSIONS: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.

Genomic surveillance uncovers ongoing transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) and identifies actionable routes of transmissions in an endemic setting.

OBJECTIVE: In our center, previous infection prevention and control (IPC) resources were concentrated on multidrug-resistant organisms other than CRAB because the rate of CRAB was stable with no evidence of outbreaks. Triggered by an increase in the baseline rate of CRAB isolated in clinical cultures, we investigated horizontal transmission of CRAB to guide targeted IPC actions. METHODS: We prospectively collected clinical data of patients with positive CRAB cultures. We identified genetic relatedness of CRAB isolates using whole-genome sequencing. Findings were regularly presented to the IPC committee, and follow-up actions were documented. RESULTS: During the study period, 66 CRAB isolates were available for WGS. Including 12 clinical isolates and 10 environmental isolates from a previous study, a total of 88 samples were subjected to WGS, of which 83 were successfully sequenced and included in the phylogenetic analysis. We identified 5 clusters involving 44 patients. Genomic transmissions were explained by spatiotemporal overlap in 12 patients and by spatial overlap only in 12 patients. The focus of transmission was deduced to be the intensive care units. One cluster was related to a retrospective environmental isolate, suggesting the environment as a possible route of transmission. Discussion of these findings at multidisciplinary IPC meetings led to implementation of measures focusing on environmental hygiene, including hydrogen peroxide vapor disinfection in addition to terminal cleaning for rooms occupied by CRAB patients. CONCLUSIONS: We showed that WGS could be utilized as a "tool of persuasion" by demonstrating the presence of ongoing transmission of CRAB in an endemic setting, and by identifying actionable routes of transmission for directed IPC interventions.

Environmental contamination in a coronavirus disease 2019 (COVID-19) intensive care unit-What is the risk?

BACKGROUND: The risk of environmental contamination by severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in the intensive care unit (ICU) is unclear. We evaluated the extent of environmental contamination in the ICU and correlated this with patient and disease factors, including the impact of different ventilatory modalities. METHODS: In this observational study, surface environmental samples collected from ICU patient rooms and common areas were tested for SARS-CoV-2 by polymerase chain reaction (PCR). Select samples from the common area were tested by cell culture. Clinical data were collected and correlated to the presence of environmental contamination. Results were compared to historical data from a previous study in general wards. RESULTS: In total, 200 samples from 20 patient rooms and 75 samples from common areas and the staff pantry were tested. The results showed that 14 rooms had at least 1 site contaminated, with an overall contamination rate of 14% (28 of 200 samples). Environmental contamination was not associated with day of illness, ventilatory mode, aerosol-generating procedures, or viral load. The frequency of environmental contamination was lower in the ICU than in general ward rooms. Eight samples from the common area were positive, though all were negative on cell culture. CONCLUSION: Environmental contamination in the ICU was lower than in the general wards. The use of mechanical ventilation or high-flow nasal oxygen was not associated with greater surface contamination, supporting their use and safety from an infection control perspective. Transmission risk via environmental surfaces in the ICUs is likely to be low. Nonetheless, infection control practices should be strictly reinforced, and transmission risk via droplet or airborne spread remains.

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.

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.

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.

Singapore SPICE: sedation practices in intensive care evaluation in Singapore - a prospective cohort study of the public healthcare system.

INTRODUCTION: A study was conducted to describe the sedation practices of intensive care units (ICUs) in Singapore in terms of drug use, sedation depth and the incidence of delirium in both early (< 48 hours) and late (> 48 hours) periods of ICU admission. METHODS: A prospective multicentre cohort study was conducted on patients who were expected to be sedated and ventilated for over 24 hours in seven ICUs (surgical ICU, n = 4; medical ICU, n = 3) of four major public hospitals in Singapore. Patients were followed up to 28 days or until ICU discharge, with four-hourly sedation monitoring and daily delirium assessment by trained nurses. The Richmond Agitation and Sedation Scale (RASS) and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) were used. RESULTS: We enrolled 198 patients over a five-month period. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 25.3 ± 9.2, and 90.9% were emergency hospital admissions. Patients were followed up for 1,417 ICU patient days, of which 396 days were in the early period and 1,021 days were in the late period. 7,354 RASS assessments were performed. Propofol and fentanyl were the sedative agents of choice in the early and late periods, respectively. Patients were mostly in the light sedation range, especially in the late period. At least one episode of delirium was seen in 23.7% of patients. CONCLUSION: Sedation practices in Singapore ICUs are characterised by light sedation depth and low incidence of delirium, possibly due to the drugs used.

Therapeutic temperature management (TTM): post-resuscitation care for adult cardiac arrest, with recommendations from the National TTM Workgroup.

Therapeutic temperature management (TTM) was strongly recommended by the 2015 International Liaison Committee on Resuscitation as a component of post-resuscitation care. It has been known to be effective in improving the survival rate and neurologic functional outcome of patients after cardiac arrest. In an effort to increase local adoption of TTM as a standard of post-resuscitation care, this paper discusses and makes recommendations on the treatment for local providers.

Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison.

BACKGROUND: The Mycobacterium tuberculosis Beijing genotype is biologically different from other genotypes. We aimed to clinically and immunologically compare human tuberculosis caused by Beijing and non-Beijing strains. METHODS: Pulmonary tuberculosis patients were prospectively enrolled and grouped by their M. tuberculosis genotypes. The clinical features, plasma cytokine levels, and cytokine gene expression levels in peripheral blood mononuclear cells (PBMC) were compared between the patients in Beijing and non-Beijing groups. RESULTS: Patients in the Beijing group were characterized by significantly lower frequency of fever (odds ratio, 0.12, p = 0.008) and pulmonary cavitation (odds ratio, 0.2, p = 0.049). Night sweats were also significantly less frequent by univariate analysis, and the duration of cough prior to diagnosis was longer in Beijing compared to non-Beijing groups (medians, 60 versus 30 days, p = 0.048). The plasma and gene expression levels of interferon (IFN) gamma and interleukin (IL)-18 were similar in the two groups. However, patients in the non-Beijing group had significantly increased IL-4 gene expression (p = 0.018) and lower IFN-gamma : IL-4 cDNA copy number ratios (p = 0.01). CONCLUSION: Patients with tuberculosis caused by Beijing strains appear to be less symptomatic than those who have disease caused by other strains. Th1 immune responses are similar in patients infected with Beijing and non-Beijing strains, but non-Beijing strains activate more Th2 immune responses compared with Beijing strains, as evidenced by increased IL-4 expression.