Dysfunctional Bronchial Cilia Are a Feature of Chronic Obstructive Pulmonary Disease (COPD).

Impaired mucociliary clearance may increase COPD exacerbation risk. We aimed to compare bronchial ciliary function and epithelial ultrastructure of COPD patients to healthy controls and explore its relationship to exacerbator phenotypes (frequent [FE] and infrequent [IFE] exacerbator). In this cross-sectional study, 16 COPD patients and 12 controls underwent bronchial brushings. Ciliary beat frequency (CBF) and dyskinesia index (DI; % of dyskinetic cilia) were assessed using digital high-speed video microscopy, and epithelial ultrastructure using transmission electron microscopy (TEM). Bronchial epithelium in COPD showed lower CBF and higher DI, compared to controls (median [IQR] CBF: 6.8 (6.1-7.2) Hz vs 8.5 (7.7-8.9) Hz, p<0.001 and DI: 73.8 (60.7-89.8) % vs 14.5 (11.2-16.9) %, p<0.001, respectively). This was true for FE and IFE phenotypes of COPD, which were similar in terms of bronchial CBF or DI. Subgroup analyses demonstrated lower CBF and higher DI in FE and IFE COPD phenotypes compared to controls, irrespective of smoking status. TEM showed more loss of cilia, extrusion of cells, cytoplasmic blebs and dead cells in COPD patients versus controls. Profound dysfunction of bronchial cilia is a feature of COPD irrespective of exacerbation phenotype and smoking status, which is likely to contribute to poor mucus clearance in COPD.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1963695 .

Use of the National Early Warning Score (NEWS) to Identify Acutely Deteriorating Patients with Sepsis in Acute Medical Ward

INTRODUCTION@#The National Early Warning Score (NEWS) is well established in acute medical units to identify acutely deteriorating patients and is shown to have good prognostic value. NEWS, however, has only been used in the Emergency Department as a triage tool. We aimed to evaluate the validity of NEWS in Acute Medical Ward (AMW) that treats predominantly acute infection-related conditions to the Internal Medicine service.@*MATERIALS AND METHODS@#We undertook a retrospective cohort study and analysed NEWS records of all patients admitted to AMW at Singapore General Hospital between 1 August 2015 and 30 July 2017. The outcome was defined as deterioration that required transfer to Intermediate Care Area (ICA), Intensive Care Unit (ICU) or death within 24 hours of a vital signs observation set.@*RESULTS@#A total of 298,743 vital signs observation sets were obtained from 11,300 patients. Area under receiver operating characteristic curve for any of the 3 outcomes (transfer to ICA, ICU or death) over a 24-hour period was 0.896 (95% confidence interval, 0.890-0.901). Event rate was noted to be high above 0.250 when the score was >9. In the medium-risk group (score of 5 or 6), event rate was <0.125.@*CONCLUSION@#NEWS accurately triages patients according to the likelihood of adverse outcomes in infection-related acute medical settings.

Making Clinical Practice Guidelines Pragmatic: How Big Data and Real World Evidence Can Close the Gap

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.

Factors associated with mortality among patients with active pulmonary tuberculosis requiring intensive care

<p><b>INTRODUCTION</b>The aim of this study was to identify patient characteristics and risk factors associated with in-hospital mortality of patients with pulmonary tuberculosis (PTB) requiring intensive care unit (ICU) management.</p><p><b>METHODS</b>A retrospective chart review was conducted of all patients with active PTB admitted to the ICU at Singapore General Hospital, Singapore, between January 2005 and December 2010.</p><p><b>RESULTS</b>There were 2,155 patients with active PTB diagnosed, of whom 83 (3.9%) patients were admitted to the ICU, but eight were excluded because their admission to the ICU was unrelated to PTB. The most common comorbidities were diabetes mellitus (n = 23, 30.7%) and immunocompromised host (n = 25, 33.3%). A few (n = 4, 5.3%) of the patients had HIV coinfection. A majority (n = 67, 89.3%) of patients required mechanical ventilation and the mean duration of mechanical ventilation was 8.05 ± 14.43 days. Mean duration of ICU stay and hospital stay were 10.23 ± 15.8 days and 33.7 ± 50.7 days, respectively. In-hospital mortality was 62.7% (n = 47), and 36 of these patients died while in the ICU (ICU mortality, 48.0%). Univariate analysis identified ischaemic heart disease, low albumin, Acute Physiology and Chronic Health Evaluation score, disseminated intravascular coagulation, shock and multiorgan failure as significantly associated with mortality. Multivariate analysis showed that low albumin on the day of ICU admission was the only significant independent predictor of death (p = 0.033).</p><p><b>CONCLUSION</b>In-hospital mortality from active PTB requiring ICU admission was 62.7%, and low albumin was an independent predictor of mortality in this study.</p>

Oesophageal Doppler ultrasound in the assessment of haemodynamic status of patients admitted to the medical intensive care unit with septic shock

<p><b>INTRODUCTION</b>Haemodynamic monitoring is an essential element in the management of critically ill patients in the intensive care unit (ICU). However, there have been increasing concerns about the clinical utility and safety profile of the invasive pulmonary artery catheter (PAC). Oesophageal Doppler (ED) monitoring has emerged recently as a safer and less invasive tool which can be used by the intensivist to estimate cardiac output in the critically ill patient. Validation studies have thus far only been performed in surgical patients perioperatively and in mixed surgical/medical ICU patients. Currently, minimal data are available in any sizeable Asian population or in patients with severe sepsis. The assumption that these normograms and data hold true for our local medical ICU patients may not be valid due to differences in body habitus.</p><p><b>MATERIALS AND METHODS</b>Our primary aim is to validate the oesophageal Doppler as a reliable measure of cardiac index, systemic vascular resistance (SVR) and preload in our local Asian population of patients with severe sepsis and septic shock in the medical ICU. This was a prospective pilot study on 12 consecutive mechanically ventilated patients in our medical ICU with the diagnosis of septic shock as defined by SCCM/ESICM/ACCP/ATS/SIS International Sepsis definitions Conference-Critical Care Medicine 2003 and required PAC haemodynamic monitoring as indicated by Medical Intensive Care Unit attending.</p><p><b>RESULTS</b>Ninety-seven paired cardiac output measurements were made. Cardiac output ranged from 2.87 to 11.0 L/ min (calculated cardiac index ranging from 1.73 to 6.36 L/min/m2) when measured using the PAC with thermodilution technique and from 2.0 to 12.1 L/min (calculated cardiac index of 1.2 to 7.2 L/min/m2) using the trans-oesophageal Doppler. There was moderately good correlation between CIpac and CIed (correlation coefficient, r = 0.762 with PCA = 58%). The mean bias was 0.26 L/min/m2 (P <0.07), while the limit of agreement was +/- 1.44 L/min/m2.</p><p><b>CONCLUSION</b>ED has good correlation with PAC in measuring cardiac index in Asians with septic shock but is an unreliable measure of both pre-load and SVR.</p>