Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD.

BACKGROUND: Variable clinical outcomes are reported with fungal sensitisation in chronic obstructive pulmonary disease (COPD), and it remains unclear which fungi and what allergens associate with the poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown. METHODS: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong. Clinical and serological assessment was performed against a panel of 35 fungal allergens including crude and recombinant Aspergillus and non-Aspergillus allergens. Unsupervised clustering and topological data analysis (TDA) approaches were employed using the measured sensitisation responses to elucidate if sensitisation subgroups exist and their related clinical outcomes. RESULTS: Aspergillus fumigatus sensitisation was associated with increased exacerbations in COPD. Unsupervised cluster analyses revealed two "fungal sensitisation" groups. The first was characterised by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group conferred even poorer outcome. The second group, characterised by Cladosporium sensitisation, was more symptomatic. Significant numbers of individuals demonstrated sensitisation responses to only recombinant (as opposed to crude) A. fumigatus allergens f 1, 3, 5 and 6, and exhibited increased exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a subgroup within Aspergillus-sensitised COPD of patients with frequent exacerbations. CONCLUSION: Aspergillus sensitisation is a treatable trait in COPD. Measuring sensitisation responses to recombinant Aspergillus allergens identifies an important patient subgroup with poor COPD outcomes that remains overlooked by assessment of only crude Aspergillus allergens.

A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD.

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain. METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi. RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality. CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.

Impact of structured curriculum with simulation on bronchoscopy.

BACKGROUND AND OBJECTIVE: Simulation enhances a physician's competency in procedural skills by accelerating ascent of the learning curve. Training programmes are moving away from the Halstedian model of 'see one, do one, teach one', also referred as medical apprenticeship. We aimed to determine if a 3-month structured bronchoscopy curriculum that incorporated simulator training could improve bronchoscopy competency among pulmonary medicine trainees. METHODS: We prospectively recruited trainees from hospitals with accredited pulmonary medicine programmes. Trainees from hospitals (A, B and C) were assigned to control group (CG) where they received training by traditional apprenticeship while trainees from hospital D were assigned to intervention group (IG) where they underwent 3-month structured curriculum that incorporated training with the bronchoscopy simulator. Two patient bronchoscopy procedures per trainee were recorded on video and scored independently by two expert bronchoscopists using the modified Bronchoscopy Skills and Tasks Assessment Tool (BSTAT) forms. A 25 multiple choice questions (MCQ) test was administered to all participants at the end of 3 months. RESULTS: Eighteen trainees participated; 10 in CG and eight in IG with equal female:male ratio. Competency assessed by modified BSTAT and MCQ tests was variable and not driven by volume as IG performed fewer patient bronchoscopies but demonstrated better BSTAT, airway anaesthesia and MCQ scores. Bronchoscopy simulator training was the only factor that correlated with better BSTAT (r = 0.80), MCQ (r = 0.85) and airway anaesthesia scores (r = 0.83), and accelerated the learning curve of IG trainees. CONCLUSION: An intensive 3-month structured bronchoscopy curriculum that incorporated simulator training led to improved cognitive and technical skill performance as compared with apprenticeship training.

The development and psychometric evaluation of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients scale.

BACKGROUND: Validated measures of ward nurses' safety cultures in relation to escalations of care in deteriorating patients are lacking. OBJECTIVES: This study aimed to develop and evaluate the psychometric properties of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients (CARED) scale for use among ward nurses. METHODS: The study was conducted in two phases: scale development and psychometric evaluation. The scale items were developed based on a systematic literature review, informant interviews, and expert reviews (n = 15). The reliability and validity of the scale were examined by administering the scale to 617 registered nurses with retest evaluations (n = 60). The factor structure of the CARED scale was examined in a split-half analysis with exploratory and confirmatory factor analyses. The internal consistency, test-retest reliability, convergent validity, and known-group validity of the scale were also analysed. RESULTS: A high overall content validity index of 0.95 was obtained from the validations of 15 international experts from seven countries. A three-factor solution was identified from the final 22 items: 'beliefs about rapid response system', 'fears about escalating care', and 'perceived confidence in responding to deteriorating patients'. The internal consistency reliability of the scale was supported with a good Cronbach's alpha value of 0.86 and a Spearman-Brown split-half coefficient of 0.87. An excellent test-retest reliability was demonstrated, with an intraclass correlation coefficient of 0.92. The convergent validity of the scale was supported with an existing validated scale. The CARED scale also demonstrated abilities to discriminate differences among the sample characteristics. CONCLUSIONS: The final 22-item CARED scale was tested to be a reliable and valid scale in the Singaporean setting. The scale may be used in other settings to review hospitals' rapid response systems and to identify strategies to support ward nurses in the process of escalating care in deteriorating ward patients.

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD.

INTRODUCTION: Allergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear. METHODS: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome. RESULTS: High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a "highly sensitised fungal predominant" subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD. CONCLUSION: Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in "sensitised" COPD.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

BACKGROUND AND OBJECTIVE: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHODS: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. RESULTS: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). CONCLUSION: Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Distinct "Immunoallertypes" of Disease and High Frequencies of Sensitization in Non-Cystic Fibrosis Bronchiectasis.

RATIONALE: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non-cystic fibrosis bronchiectasis remain unclear. OBJECTIVES: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. METHODS: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined. MEASUREMENTS AND MAIN RESULTS: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. CONCLUSIONS: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.

A call for better doctor-nurse collaboration: A qualitative study of the experiences of junior doctors and nurses in escalating care for deteriorating ward patients.

BACKGROUND: Despite the widespread implementation of medical emergency teams (METs) in hospitals to provide immediate interventions to deteriorating ward patients, little is known about how junior doctors and nurses escalate care for deteriorating ward patients in hospitals with established MET services. OBJECTIVES: The objective of this research study was to explore the experiences of junior doctors and nurses in escalating care for clinically deteriorating patients in general wards. METHODS: Twenty-four individual interviews were conducted with 10 junior doctors and 14 registered nurses of a 1000-bed acute general hospital with the most established MET service in Singapore. Interviews were transcribed verbatim and analysed using an interpretive thematic analysis approach. FINDINGS: Three salient themes emerged from thematic analysis: (1) MET activations versus the primary team doctors' reviews, (2) challenges in obtaining medical reviews, and (3) unspoken rules of the escalation of care. Participants' decisions to call the MET or to escalate to the primary team doctors not only depended on the severity of a patient's deterioration and their perceptions of the primary team doctors' capacity to manage the patient but also were largely influenced by sociocultural factors that were shaped by the hierarchy of medical professions. Key challenges faced by nurses in obtaining medical reviews from junior doctors for patients with early deterioration included presenting "convincing" evidence of patient deterioration and "packaging" information about patient deterioration. CONCLUSIONS: The decision to call a MET or the primary team doctors is a complex judgement that is greatly influenced by the dynamics of perceived hierarchy between the medicine and nursing professions and within the medicine profession. Educational and organisational changes that enhance doctor-nurse interprofessional and intraprofessional collaboration among all levels of doctors may improve the process of the escalation of care for deteriorating patients and thus improve patient safety for hospitalised patients.

Predictors of future exacerbations in a multi-ethnic Asian population with asthma.

OBJECTIVE: Exacerbations are important outcomes in asthma. Risk factors for exacerbations may differ in different populations. Although various demographic and clinical variables were examined in previous studies on exacerbation risks in asthma, important variables such as ethnicity, adherence, and medication titration were not included. This study examined independent predictors of future exacerbations in a multi-ethnic asthma population in Asia, while including the variables of ethnicity, medication adherence, and medication change in our analysis. METHODS: We recruited patients with physician-diagnosed asthma in a tertiary hospital in Singapore over a one-year period. Exacerbations requiring ≥3 days of systemic corticosteroids one year prior to study enrolment (previous exacerbations) and the year following enrolment (future exacerbations) were recorded from electronic medical records. Medication adherence was based on pharmacy refill. An increase or a decrease in the Global Initiative for Asthma treatment steps were considered to be medication up- and down-titration, respectively. A multivariate logistic regression model was constructed to determine independent predictors of future exacerbations. RESULTS: The study cohort of 340 patients comprised mainly of Chinese (53.2%), Malay (32.9%), and Indian (9.7%) ethnicities. After multivariate analysis, only Indian ethnicity (OR 3.75, 95% CI 1.077-13.051, p = 0.038), Asthma Control Test score (OR 0.913, 95% CI 0.839-0.995, p = 0.037), and the number of previous exacerbations (OR 1.84, 95% CI 1.416-2.391, p < 0.001) were independent predictors of future exacerbations. CONCLUSIONS: There are ethnic differences in exacerbation risk in Asian populations. Each incremental worsening of the asthma symptom control score and each additional exacerbation also increases the risk of future exacerbations.

Characteristics of non-smoking adult asthma patients with chronic airflow limitation.

OBJECTIVE: Chronic airflow limitation (CAL) can develop in a subgroup of patients with asthma. Characterising these patients is important because reduced lung function is a risk factor for adverse asthma outcomes. We hypothesised that heterogeneity in patients with CAL may be influenced by age at asthma onset. We first compared never-smoking asthma patients with and without CAL, and subsequently examined the differences between patients with late and early-onset asthma within the CAL cohort. METHODS: Patients seen in our hospital's respiratory clinic between 1 Jan 2015 and 31 December 2015 were recruited to the study. CAL was defined as post-bronchodilator forced expiratory volume in 1 second (FEV1)<80% predicted, in the presence of post-bronchodilator ratio <70%. Variables independently associated with CAL were determined using a multivariate logistic regression model. Comparisons between patients with late-onset asthma (age ≥18 years) and early-onset asthma were made within the CAL cohort. RESULTS: 247 patients were included in the study. Age was the only variable independently associated with CAL after regression analysis, with an increase in odds of 3.8% (95% CI 0.4-7.3%) for every 1 year increase in age, p = 0.027. 63.2% of patients with CAL had late-onset asthma. Compared to patients with early-onset asthma, those with late-onset asthma had higher fractional exhaled nitric oxide levels (43 ± 32 ppb vs 20 ± 8 pb, p = 0.008). CONCLUSIONS: An increase in age is associated with CAL in never-smoking asthma patients. In addition, age at asthma onset appears to influence airway inflammation in patients with CAL.

Factors influencing the activation of the rapid response system for clinically deteriorating patients by frontline ward clinicians: a systematic review.

PURPOSE: To synthesize factors influencing the activation of the rapid response system (RRS) and reasons for suboptimal RRS activation by ward nurses and junior physicians. DATA SOURCES: Nine electronic databases were searched for articles published between January 1995 and January 2016 in addition to a hand-search of reference lists and relevant journals. STUDY SELECTION: Published primary studies conducted in adult general ward settings and involved the experiences and views of ward nurses and/or junior physicians in RRS activation were included. DATA EXTRACTION: Data on design, methods and key findings were extracted and collated. RESULTS OF DATA SYNTHESIS: Thirty studies were included for the review. The process to RRS activation was influenced by the perceptions and clinical experiences of ward nurses and physicians, and facilitated by tools and technologies, including the sensitivity and specificity of the activation criteria, and monitoring technology. However, the task of enacting the RRS activations was challenged by seeking further justification, deliberating over reactions from the rapid response team and the impact of workload and staffing. Finally, adherence to the traditional model of escalation of care, support from colleagues and hospital leaders, and staff training were organizational factors that influence RRS activation. CONCLUSION: This review suggests that the factors influencing RRS activation originated from a combination of socio-cultural, organizational and technical aspects. Institutions that strive for improvements in the existing RRS or are considering to adopt the RRS should consider the complex interactions between people and the elements of technologies, tasks, environment and organization in healthcare settings.

A comparison of GOLD 2019 and 2023 recommendations to contemporaneous real-world inhaler treatment patterns for chronic obstructive pulmonary disease management in Singapore.

Background: In 2019 and 2023, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) provided updated strategies for modifying the therapy of patients with chronic obstructive pulmonary disease (COPD) and high exacerbation risk. A key update since the 2019 guidelines recommends considering blood eosinophil count to guide decisions on inhaled corticosteroid (ICS) treatment. To evaluate the potential impact of these updated recommendations, this study aimed to assess how extensively future practice would diverge from contemporaneous prescribing practices at a single center in Singapore, assuming adherence to the 2019 and 2023 GOLD guidelines. Methods: Retrospective cohort analysis of the Changi General Hospital COPD data warehouse involving patients aged ≥40 years hospitalized for a COPD exacerbation (October 2018-April 2020) receiving long-acting muscarinic antagonist (LAMA), LAMA plus a long-acting beta2-agonist (LABA), or an ICS plus LABA at admission. The proportion of patients eligible for treatment escalations per GOLD 2019 and 2023 recommendations was calculated. Results: In total, 268 patients were included (mean age 73 years; 91% male). At admission, 19%, 59%, and 22% of patients were receiving LAMA, LAMA + LABA, and ICS + LABA, respectively. Overall, 226 patients would have been eligible for treatment escalation per GOLD 2019 or 2023 recommendations; 31 (13.7%) had treatment escalations consistent with GOLD 2019 guidelines and 34 (15%) received treatment escalations consistent with GOLD 2023 guidelines. A total of 205 patients (76.5%) remained on the same treatment regimen at hospital discharge as they were receiving at admission. Lower measured post-bronchodilator forced expiratory volume in 1 second was associated with treatment escalations that would have been GOLD-concordant (P=0.028), as was increased number of emergency department/hospital visits in the last year (P=0.048). Conclusions: Compared with real-world clinical practice, a significantly higher proportion of patients may be eligible for treatment escalation under the GOLD 2019 and 2023 eosinophil-directed algorithms.

Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: a retrospective cohort study.

BACKGROUND: Adenosine deaminase (ADA) is useful in the diagnosis of tuberculous pleural effusion (TPE). This study aims to determine the factors affecting pleural fluid ADA levels and to establish the optimal ADA levels for diagnosis of TPE for different age groups. METHODS: This was a retrospective study from January 2007 to October 2011. One hundred and sixty patients who had pleural fluid ADA performed for investigation of pleural effusion were analyzed. Variables examined included demographics, pleural fluid characteristics and peripheral blood counts. The ADA cut-offs according to age were selected using the receiver operating characteristic (ROC) curve. RESULTS: The mean pleural fluid ADA was significantly higher in the TPE group (100 ± 35 IU/L) compared to non TPE patients (30 ± 37 IU/L). There was significant correlation between pleural fluid ADA and age, pleural fluid protein, LDH, and fluid absolute lymphocyte count. The strongest correlation was seen with age (r = -0.621). For patients ≤ 55 years old the ROC for ADA had area under curve (AUC) of 0.887. A pleural fluid ADA of 72 IU/L had sensitivity of 95.1%, specificity of 87.5%, positive predictive value (PPV) of 95.1% and negative predictive value (NPV) of 87.5% for the diagnosis of TPE. For patients > 55 years old the AUC is 0.959. ADA of 26 IU/L had a sensitivity of 94.7%, specificity of 80.4%, PPV of 62% and NPV of 97.8%. CONCLUSIONS: There is a significant negative correlation between pleural fluid ADA and age. For older patients, a lower ADA cut-off should be used to exclude TPE.

Association between proximity to COVID-19 and the quality of life of healthcare workers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) affects almost all countries in the world and it impacts every aspect of people's life-physically, mentally, and socio-economically. There are several research studies examining the impact of this pandemic on health, however, very few studies examining the impact of this pandemic on quality of life. This study aimed to investigate the association between proximity to the COVID-19 and quality of life of healthcare workers and identify factors influencing quality of life. METHODS: A cross-sectional study was conducted among hospital staff in a tertiary hospital in Singapore. Data on demographic, medical history, lifestyle factors, psychosocial factors, and quality of life were collected using online self-administered questionnaire. Quality of life (QoL) was measured by the WHOQOL-BREF questionnaire. Robust linear regression was used to determine factors associated with quality of life. RESULTS: A total of 1911 participants were included in the analysis. The average age of participants was 38.25 (SD = 11.28) years old. 26.90% of participants had been quarantined, hospitalised, being suspected or diagnosed of having COVID-19 infection and they were found to have the lowest levels of QoL across all four domains (physical, psychological, social, and environmental domains). Participants who were singles or nurses, worked in shifts or worked longer hours, had chronic diseases were likely to have lower QoL scores compared to participants in other categories. Healthy lifestyle, social connectivity, resilience, social and workplace support were associated with higher QoL scores. CONCLUSIONS: In planning of measures which aim to improve QoL of healthcare workers, priority should be given to individuals who have been quarantined, hospitalised, being suspected, or diagnosed of having COVID-19 infection. In addition to the proximity of the COVID, lifestyle and psychosocial factors contribute to QoL of healthcare workers. Hence, multifaceted interventions are needed to improve QoL of healthcare workers.

Year-to-year trajectories of hospital utilisation rates among patients with COPD: a real-world, single-centre, retrospective cohort study.

OBJECTIVES: The long-term clinical trajectory of chronic obstructive pulmonary disease (COPD) in terms of year-to-year hospital utilisation rates can be highly variable and is not well studied. We investigated year-to-year trends of hospitalisation or emergency department (ED) visits among patients with COPD over 3 years, identified distinct trajectories and examined associated predictive factors. DESIGN: A retrospective cohort study. SETTING: Data were extracted from the Changi General Hospital, Singapore COPD data warehouse. PARTICIPANTS: Patients with COPD aged ≥40 years with 3 years of follow-up data. PRIMARY AND SECONDARY OUTCOME MEASURES: The yearly rates of hospitalisations or ED visits, stratified by COPD-related or all-cause, were described. Group-based trajectory modelling was used to identify clinically distinct trajectories year-by-year. Baseline predictive factors associated with different trajectories were examined. RESULTS: In total, 396 patients were analysed (median age 70 years; 87% male). Four trajectories were generated for year-to-year trends in COPD-related hospitalisations/ED visits (C1-C4: consistently frequent, consistently infrequent, improving and worsening); post-bronchodilator forced expiratory volume in 1 second (FEV1) was a significant predictor of trajectory, with worse lung function being the main factor associated with less favourable trajectories. For all-cause hospitalisations/ED visits, four trajectories were identified (A1-A4: infrequent and stable, frequent and stable, frequent and decreasing, frequent and increasing); significant differences in age (p=0.041), sex (p=0.016) and ethnicity (p=0.005) were found between trajectories. Higher overall comorbidity burden was a key determinant in less favourable trajectories of all-cause hospitalisations/ED visits. CONCLUSIONS: Distinct trajectories were demonstrated for hospitalisations/ED visits related to COPD or all causes, with predictive associations between FEV1 and COPD trajectory and between comorbidities and all-cause trajectory. Trajectories carry nuanced prognostic information and may be useful for clinical risk stratification to identify high-risk individuals for preventative treatments.

Findings from a decade of experience following implementation of a Rapid Response System into an Asian hospital.

Aim: Rapid response systems (RRS) are present in many acute hospitals in western nations but are not widely adopted in Asia. The influence of healthcare culture and the effect of implementing an RRS over time are infrequently reported. We describe the introduction a RRS into a Singaporean hospital and the barriers encountered. The efferent limb activation rates, cardiac arrest rates and unplanned intensive care unit (ICU) admissions are trended over eleven years. Methods: We conducted a retrospective observational study using prospectively collected data derived from administrative and Medical Emergency Team (MET) databases. Results: The RRS used a MET with a single parameter track and trigger and physician led efferent limb. Barriers encountered included clinical leadership buy-in, assembling and equipping the efferent team, maintaining a non-punitive mindset, improving accessibility to MET and communicating the impact of the MET. Over an 11-year period with 488,252 hospital admissions, MET activation rates increased from 1.6/1000 admissions (2009) to 14.1/1000 admissions (2019). Code blue activations and unplanned ICU admission rates decreased from 2.9 to 1.7 and from 8.8 to 2.0/1000 admissions, respectively over the 11 years. There were associations between increasing MET activation rate and reduction in code blue activations (p = 0.013) and unplanned medical ICU admission rates (p = 0.001). Conclusion: Implementing, sustaining and continued improvement of an RRS in Singapore is possible despite challenges encountered. With increasing activation rates over a decade, there were reductions in cardiac arrest rates and unplanned medical ICU admissions.

Female reproductive factors, gene polymorphisms in the estrogen metabolism pathway, and risk of lung cancer in Chinese women.

The authors examined relations between reproductive factors and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ERß rs1256049, ERß rs4986938, and COMT rs4680) among 702 Singapore Chinese female lung cancer cases and 1,578 hospital controls, of whom 433 cases (61.7%) and 1,375 controls (87.1%) were never smokers. Parity (per child, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87, 0.97) and menstrual cycle length (for ≥30 days vs. <30 days, OR = 0.50, 95% CI: 0.32, 0.80) were inversely associated with lung cancer in never smokers, while age at first birth (for ages 21-25, 26-30, and ≥31 years vs. ≤20 years, ORs were 1.54, 2.17, and 1.30, respectively), age at menopause (for ages 49-51 and ≥52 years vs. ≤48 years, ORs were 1.37 and 1.59; P(trend) = 0.003), and reproductive period (for 31-33, 34-36, 37-39, and ≥40 years vs. ≤30 years, ORs were 1.06, 1.25, 1.45, and 1.47; P(trend) = 0.026) were positively associated. Among smokers, parity was inversely associated with lung cancer, but there was no association with other reproductive factors. The COMT rs4680 A allele was positively associated with lung cancer in never smokers (for G/A or A/A vs. G/G, OR = 1.46, 95% CI: 1.12, 1.90) but not in ever smokers. No associations were seen with other polymorphisms. These results support a risk-enhancing role of estrogens in lung carcinogenesis among never smokers.

Point-of-care measurement of serum creatinine in the intensive care unit.

OBJECTIVE: To test the precision and limits of agreement of point-of-care testing (POCT)-based measurement of serum creatinine (Cr) in critically ill patients. METHODS: We studied 250 paired blood samples from 82 critically ill patients from a general intensive care unit by simultaneous POCT and central laboratory testing (Jaffé method). Correlation, precision, bias, and limits of agreement were assessed. Possible confounders for interference of noncreatinine chromogens were evaluated by multivariate linear regression analysis. RESULTS: The mean difference in serum Cr measured by central laboratory and POCT was +9.6 µmol/L (95% limits of agreement: -11.2 to +30.4 µmol/L). The mean percentage difference between the two techniques was 8.7% (95% limits of agreement -7.8% to +25.1%). On multivariate regression, the difference in serum Cr was increased with greater hemoglobin and lactate levels but decreased with greater bilirubin, albumin, and calcium levels. CONCLUSIONS: Compared with the central laboratory testing, POCT-based measurement of serum Cr in critically ill patients carried a small negative bias. This difference appeared affected by the blood levels of biochemical variables known to affect the Jaffé method. POCT-based Cr measurement appears sufficiently accurate for clinical use.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease Treated with Long-Acting Bronchodilators in a Real-World Setting in Singapore: A Single-Center Observational Study.

Introduction: There is limited real-world evidence regarding clinical practice for chronic obstructive pulmonary disease (COPD) in Singapore. We compared baseline clinical characteristics and evaluated outcomes in patients with COPD who initiated treatment with either a long-acting muscarinic antagonist (LAMA) or a LAMA and a long-acting ß2-agonist (LAMA+LABA). Methods: This was a single-center observational study at Changi General Hospital, Singapore. Routine clinical data (hospital visits, case management, lung function, laboratory/imaging results, medication orders) were collected and compiled into a data warehouse. Eligible patients with COPD were ≥40 years old and newly prescribed LAMA or LAMA+LABA during the enrollment period. Patient characteristics in the baseline period (6 months) were compared between treatments. Clinical worsening was measured as a composite endpoint, defined as the first of a change in maintenance treatment class or a moderate-to-severe exacerbation during follow-up (12 months). Results: In total, 261 patients were included in the baseline period (LAMA: 73; LAMA+LABA: 188). In the baseline period, patients receiving LAMA+LABA versus LAMA had significantly lower body mass index, higher COPD Assessment Test score and worse lung function, and numerically higher exacerbation history. Prevalence of comorbidities was similar between treatment groups. In follow-up, high rates of clinical worsening were observed regardless of treatment regimen (LAMA: 38/73 [52%]; LAMA+LABA: 86/188 [46%]). Median time-to-clinical worsening was 340 days for the LAMA cohort and the raw median 154 days (interquartile range: 44-225) for the LAMA+LABA cohort. Median medication dispensation rate (0.86; interquartile range: 0.56-1.00) was similar between treatments. Conclusion: Patients initiating treatment with LAMA+LABA had more severe COPD than patients prescribed LAMA. The proportion of patients experiencing clinical worsening was similarly high in both cohorts, suggesting that early identification and treatment optimization are necessary.