INTRODUCTION: Singapore was one of the first countries affected by the coronavirus disease 2019 (COVID-19) pandemic but has been able to prevent its healthcare system and intensive care units (ICU) from being overwhelmed. We describe the clinical features, management and outcomes of COVID-19 patients with respiratory failure admitted to our ICU. MATERIALS AND METHODS: A case series of COVID-19 patients admitted to our ICU for respiratory failure from 7 February, with data censoring at 30 June 2020, was performed from a review of medical records. RESULTS: Twenty-two COVID-19 patients were admitted to our ICU for respiratory failure. The median age was 54.5 years (IQR 30-45.5), 72.7% were male and had at least one comorbidity. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 2.5 (IQR 1.25-7) and 10 (8.25-12) respectively. Thirteen patients required invasive mechanical ventilation (IMV) and had a median PaO2/FiO2 ratio of 194 mmHg (IQR 173-213) after intubation. The 28-day survival was 100%, with 2 patients demising subsequently. The overall ICU mortality rate was 9.1% at the time of data censoring. In IMV survivors, length of IMV and ICU stay were 11 days (IQR 9-17.75) and 16 days (IQR 12-32) respectively. CONCLUSION Low COVID-19 ICU mortality was observed in our "pandemic-ready" ICU. This was achieved by having adequate surge capacity to facilitate early ICU admission and IMV, lung protective ventilation, and slow weaning. Being able to maintain clinical standards and evidence-based practices without having to resort to rationing contributed to better outcomes.
APACHE ; Adult ; Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; therapy ; Critical Care ; organization & administration ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; therapy ; Respiration, Artificial ; Respiratory Insufficiency ; mortality ; therapy ; virology ; Retrospective Studies ; Singapore

Clinical practice guidelines (CPGs) have become ubiquitous in every field of medicine today but there has been limited success in implementation and improvement in health outcomes. Guidelines are largely based on the results of traditional randomised controlled trials (RCTs) which adopt a highly selective process to maximise the intervention's chance of demonstrating efficacy thus having high internal validity but lacking external validity. Therefore, guidelines based on these RCTs often suffer from a gap between trial efficacy and real world effectiveness and is one of the common reasons contributing to poor guideline adherence by physicians. "Real World Evidence" (RWE) can complement RCTs in CPG development. RWE-in the form of data from integrated electronic health records-represents the vast and varied collective experience of frontline doctors and patients. RWE has the potential to fill the gap in current guidelines by balancing information about whether a test or treatment works (efficacy) with data on how it works in real world practice (effectiveness). RWE can also advance the agenda of precision medicine in everyday practice by engaging frontline stakeholders in pragmatic biomarker studies. This will enable guideline developers to more precisely determine not only whether a clinical test or treatment is recommended, but for whom and when. Singapore is well positioned to ride the big data and RWE wave as we have the advantages of high digital interconnectivity, an integrated National Electronic Health Record (NEHR), and governmental support in the form of the Smart Nation initiative.
Big Data ; Electronic Health Records ; Evidence-Based Medicine ; Guideline Adherence ; Humans ; Practice Guidelines as Topic ; Practice Patterns, Physicians' ; Pragmatic Clinical Trials as Topic ; Precision Medicine ; Singapore

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality. METHODS: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented. RESULTS: A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, CONCLUSION The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.
Aged ; Bronchiectasis/epidemiology* ; Cohort Studies ; Female ; Fibrosis ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pulmonary Medicine ; Severity of Illness Index ; Singapore/epidemiology*

No abstract available.
Lung Diseases, Interstitial

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser2P),and Ser5-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser5P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rifl.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interact-ing with RNA Pol Ⅱ Ser2P and Ser5P.