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Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged hospitalisation, excessive antibiotic use and, consequently, increased antimicrobial resistance. In this phase 4, randomised trial, we aimed to establish whether a pragmatic, individualised, short-course antibiotic treatment strategy for VAP was non-inferior to usual care. We did an individually randomised, open-label, hierarchical non-inferiority–superiority trial in 39 intensive care units in six hospitals in Nepal, Singapore, and Thailand. We enrolled adults (age ≥18 years) who met the US Centers for Disease Control and Prevention National Healthcare Safety Network criteria for VAP, had been mechanically ventilated for 48 h or longer, and were administered culture-directed antibiotics. In culture-negative cases, empirical antibiotic choices were made depending on local hospital antibiograms reported by the respective microbiology laboratories or prevailing local guidelines. Participants were assessed until fever resolution for 48 h and haemodynamic stability, then randomly assigned (1:1) to individualised short-course treatment (≤7 days and as short as 3–5 days) or usual care (≥8 days, with precise durations determined by the primary clinicians) via permuted blocks of variable sizes (8, 10, and 12), stratified by study site. Independent assessors for recurrent pneumonia and participants were masked to treatment allocation, but clinicians were not. The primary outcome was a 60-day composite endpoint of death or pneumonia recurrence. The non-inferiority margin was prespecified at 12% and had to be met by analyses based on both intention-to-treat (all study participants who were randomised) and per-protocol populations (all randomised study participants who fulfilled the eligibility criteria, met fitness criteria for antibiotic discontinuation, and who received antibiotics for the duration specified by their allocation group). This study is registered with ClinicalTrials.gov , number NCT03382548. Between May 25, 2018, and Dec 16, 2022, 461 patients were enrolled and randomly assigned to the short-course treatment group (n=232) or the usual care group (n=229). Median age was 64 years (IQR 51–74) and 181 (39%) participants were female. 460 were included in the intention-to-treat analysis after excluding one withdrawal (231 in the short-course group and 229 in the usual care group); 435 participants received the allocated treatment and fulfilled eligibility criteria, and were included in the per-protocol population. Median antibiotic treatment duration for the index episodes of VAP was 6 days (IQR 5–7) in the short-course group and 14 days (10–21) in the usual care group. 95 (41%) of 231 participants in the short-course group met the primary outcome, compared with 100 (44%) of 229 in the usual care group (risk difference –3% [one-sided 95% CI −∞ to 5%]). Results were similar in the per-protocol population. Non-inferiority of short-course antibiotic treatment was met in the analyses, although superiority compared with usual care was not established. In the per-protocol population, antibiotic side-effects occurred in 86 (38%) of 224 in the usual care group and 17 (8%) of 211 in the short-course group (risk difference –31% [95% CI –37 to –25%; p<0·0001]). In this study of adults with VAP, individualised shortened antibiotic duration guided by clinical response was non-inferior to longer treatment durations in terms of 60-day mortality and pneumonia recurrence, and associated with substantially reduced antibiotic use and side-effects. Individualised, short-course antibiotic treatment for VAP could help to reduce the burden of side-effects and the risk of antibiotic resistance in high-resource and resource-limited settings. UK Medical Research Council; Singapore National Medical Research Council. For the Thai and Nepali translations of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation. Aim: To elucidate the relationship between a spot blood eosinophil count–measured at the onset of a life‐threatening asthma exacerbation–with indices of exacerbation severity and risk of subsequent exacerbations. Methods: Real‐world, retrospective review of all life‐threatening asthma cases admitted at 4 public hospitals in Singapore between 2011‐2015. We assessed the trends and correlations between blood eosinophil count on admission with arterial blood gas values, duration of mechanical ventilation, and risk of death, hypoxic ischemic encephalopathy or respiratory arrest. Risk of future exacerbations among survivors was modelled using Cox regression and survival curves. Results: There were 376 index life‐threatening exacerbations with median blood eosinophil count (5‐95th percentiles) of 0.270 × 109/L (0‐1.410 × 109/L). Arterial pH decreased and PCO2 increased with increasing eosinophil count. Duration of mechanical ventilation and risk of death, hypoxic ischaemic encephalopathy or respiratory arrest did not vary with eosinophils. Among 329 survivors who were followed‐up over a median of 52 months, blood eosinophils ≥1.200 × 109/L was associated with an increased hazard of emergency visits and/or admissions for asthma (hazard ratio 1.8, 95% confidence interval 1.1‐2.9, P =.02). Conclusion: In this study of life‐threatening asthma, we found that a spot blood eosinophil count correlates with severity of respiratory failure and predicts risk of subsequent exacerbations. [ABSTRACT FROM AUTHOR]

In this study we examined whether past research on social desirability based on western samples could be generalized to a novel environment, such as Singapore. We also investigated whether cultural orientations predict the inflation of personality scores in the selection process and whether they influence the effectiveness of social desirability correction. Using survey data collected at two points from 324 undergraduate business students (166 students from the United States and 158 students from Singapore), the results of this within-subject design study were mixed. Specifically, while social desirability inflated scores on personality measures, it also increased their criterion validity in Singapore. Additionally, self-deception enhancement ( SDE) predicted the inflation of openness to experience scores in the United States. Finally, in the sample from the United States, correcting for SDE increased the criterion validity of personality measures to a greater extent for those who scored high on horizontal individualism ( HI) than it did for those who scored low on HI. [ABSTRACT FROM AUTHOR]

Background: The REGARD-VAP trial showed that individualised shortened antibiotic therapy was non-inferior to usual care for mortality and pneumonia recurrence in patients with ventilator-associated pneumonia (VAP). We aimed to assess the cost-effectiveness of an individualised shortened antibiotic therapy approach in this planned economic analysis., Methods: REGARD-VAP was a phase 4, multicentre, open-label, randomised trial to assess a short-course antibiotic treatment strategy for treatment of VAP. In this planned economic analysis, we fitted a decision tree with data from the REGARD-VAP trial to estimate the cost-effectiveness of individualised short-course therapy for VAP, compared to usual care from the health system perspective, in Nepal, Singapore, and Thailand. Incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits with 95% uncertainty intervals (UIs) were reported against relevant willingness-to-pay thresholds. Parameter uncertainties were evaluated using scenario analyses. A value of information analysis was conducted., Findings: Adopting individualised short-course therapy was cost-effective for Nepal (ICER=US$1086; percentage cost-effectiveness=50·3%), Singapore (ICER=-$6069; percentage cost-effectiveness=55·2%), and Thailand (ICER=$263; percentage cost-effectiveness=60·5%). The associated incremental net monetary benefits were $41 (95% UI -2308 to 2390) in Nepal, $5156 (-45 805 to 56 117) in Singapore, and $804 (-6245 to 7852) in Thailand. Value of information analysis showed that reducing uncertainties for mortality probabilities, bed-day costs, and variable costs were valuable for decision making., Interpretation: We found that an individualised short-course antibiotics strategy in patients with VAP is likely to be cost-effective in high-income, middle-income, and low-income settings, although with evident uncertainty. Considered alongside the positive externalities of reduced antimicrobial use, our findings foster confidence in policy makers contemplating adoption of short-course antibiotics., Funding: UK Medical Research Council, Singapore National Medical Research Council, and Wellcome Trust., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Anticoagulation is recommended during continuous kidney replacement therapy (CKRT) to prolong the filter lifespan for optimal filter performance. We aimed to evaluate the effect of anticoagulation during CKRT on dialysis dependence and mortality within 90 days of intensive care unit (ICU) admission., Method: Our retrospective observational study evaluated the first CKRT session in critically ill adults with acute kidney injury (AKI) in Singapore from April to September 2017. The primary outcome was a composite of dialysis dependence or death within 90 days of ICU admission; the main exposure variable was anticoagulation use (regional citrate anticoagulation [RCA] or systemic heparin). Multivariable logistic regression was performed to adjust for possible confounders: age, female sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, liver dysfunction, coagulopathy (international normalised ratio[INR] >1.5) and platelet counts of less than 100,000/uL)., Results: The study cohort included 276 patients from 14 participating adult ICUs, of whom 176 (63.8%) experienced dialysis dependence or death within 90 days of ICU admission (19 dialysis dependence, 157 death). Anticoagulation significantly reduced the odds of the primary outcome (adjusted odds ratio [AOR] 0.47, 95% confidence interval [CI] 0.27-0.83, P=0.009). Logistic regression analysis using anticoagulation as a 3-level indicator variable demonstrated that RCA was associated with mortality reduction (AOR 0.46, 95% CI 0.25-0.83, P=0.011), with heparin having a consistent trend (AOR 0.51, 95% CI 0.23-1.14, P=0.102)., Conclusion: Among critically ill patients with AKI, anticoagulation use during CKRT was associated with reduced dialysis or death at 90 days post-ICU admission, which was statistically significant for regional citrate anticoagulation and trended in the same direction of benefit for systemic heparin anticoagulation. Anticoagulation during CKRT should be considered whenever possible., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

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 (FiO 2 ), higher partial pressure of oxygen to FiO 2 ratio, and higher oxygen saturation to FiO 2 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 FiO 2 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., Competing Interests: Conflict of interest Dr Matthew Cove received consultancy fees from Baxter and Medtronic which are paid directly to the institution. The other authors have no financial or personal interests to declare., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

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.

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.

Introduction: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICUs). Using short-course antibiotics to treat VAP caused by Gram-negative non-fermenting bacteria has been reported to be associated with excess pneumonia recurrences. The "REducinG Antibiotic tReatment Duration for Ventilator-Associated Pneumonia" (REGARD-VAP) trial aims to provide evidence for using a set of reproducible clinical criteria to shorten antibiotic duration for individualised treatment duration of VAP., Methods and Analysis: This is a randomised controlled hierarchical non-inferiority-superiority trial being conducted in ICUs across Nepal, Thailand and Singapore. The primary outcome is a composite endpoint of death and pneumonia recurrence at day 60. Secondary outcomes include ventilator-associated events, multidrug-resistant organism infection or colonisation, total duration of antibiotic exposure, mechanical ventilation and hospitalisation. Adult patients who satisfy the US Centers for Disease Control and Prevention National Healthcare Safety Network VAP diagnostic criteria are enrolled. Participants are assessed daily until fever subsides for >48 hours and have stable blood pressure, then randomised to a short duration treatment strategy or a standard-of-care duration arm. Antibiotics may be stopped as early as day 3 if respiratory cultures are negative, and day 5 if respiratory cultures are positive in the short-course arm. Participants receiving standard-of-care will receive antibiotics for at least 8 days. Study participants are followed for 60 days after enrolment. An estimated 460 patients will be required to achieve 80% power to determine non-inferiority with a margin of 12%. All outcomes are compared by absolute risk differences. The conclusion of non-inferiority, and subsequently superiority, will be based on unadjusted and adjusted analyses in both the intention-to-treat and per-protocol populations., Ethics and Dissemination: The study has received approvals from the Oxford Tropical Research Ethics Committee and the respective study sites. Results will be disseminated to patients, their caregivers, physicians, the funders, the critical care societies and other researchers., Trial Registration Number: NCT03382548., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background and Objective: Guidelines for chronic obstructive pulmonary disease (COPD) advocate regular influenza vaccination, which has been shown to reduce exacerbations. However, influenza vaccination rates remain low. This quality improvement project was initiated to help improve influenza vaccination rates in a tertiary hospital., Methods: All patients with COPD in the airway program (TAP) in the National University Hospital at the end of 2013 were recruited. The interventions were implemented in 2014; thus, population was stratified into the pre-intervention group and post-intervention group. Those who died in 2014 were excluded. They were (1) patient education posters in the clinics on the need for regular influenza vaccination, (2) direct interventions by physicians, and (3) intervention by the nurses when vaccinations were neglected. Physicians were made aware of previous vaccination rates, vaccination card reminders were placed in the clinics, and a new electronic healthcare record system (EHR) was implemented. The patients were followed up till the end of 2015 or until death. When an influenza vaccination was administered, the patients were asked which of the interventions led to the vaccination. A questionnaire was delivered to the physicians to determine the interventions that led to any change in vaccination prescription practices., Results: The pre-intervention influenza vaccination rate was low at 47.7%. The post-intervention influenza vaccination rate improved to 80.7% with the multi-pronged approach. Physicians initiated the majority of vaccinations (87.9%), while nurses helped intervene in a further 12.1%. Physicians' vaccination prescription practices changed as a result of self-awareness of low vaccination rates, vaccination card reminders, and the new EHR. Patient education made minimal impact., Conclusion: This project demonstrates that with regular audits to track progress and several easy-to-implement interventions, improving influenza vaccination rates is an achievable goal., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2019 Li et al.)