Multidisciplinary simulation training for endotracheal intubation during COVID-19 in one Hong Kong regional hospital: strengthening of existing procedures and preparedness.

Introduction: In early 2020, our hospital responded with high alertness when novel coronavirus SARS-CoV-2 appeared. A hospital-based training programme was rapidly arranged to prepare staff for the imminent threat. Objective: We developed a hospital-wide multidisciplinary infection control training programme on endotracheal intubation for healthcare workers to minimise nosocomial spread of COVID-19 during this high-stress and time-sensitive risky procedure. Methodology: Major stakeholders (Quality & Safety Department, Infection Control Team, Central Nursing Division, high-risk clinical departments and hospital training centre) formed a training programme task group. This group was tasked with developing high-fidelity scenario-based simulation training curriculum for COVID-19 endotracheal intubation with standard workflow and infection control practice. This group then implemented and evaluated the training programme for its effectiveness. Results: 101 training classes of 2-hour session were conducted from 5 February to 18 March 2020, involving 1415 hospital staff (~81% of target participants with training needs) either inside the hospital training centre or as in situ simulation training (intensive care unit or accident and emergency department). Learners' satisfaction was reflected by overall positive response percentage at 90%. Opinions of participating staff were incorporated into the standard airway management and infection control practice for endotracheal intubation of adult patients with COVID-19. Thirty-five patients with COVID-19 were intubated with the current workflow and guideline without any nosocomial transmission. Conclusion: An early planned and well-structured multidisciplinary hospital-wide simulation training programme was organised expeditiously to provide extensive staff coverage. The insight and experience gained from this project is valuable for future infectious disease challenges.

Periventricular white matter hyperintensity burden and cognitive impairment in early Parkinson's disease.

BACKGROUND AND PURPOSE: This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson's disease (PD) and explored their associations with cardiovascular risk factors and cognitive performance. METHODS: A total of 175 non-demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD-MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10-year cardiovascular risk score (mFRS). RESULTS: A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD-MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P = 0.015) and periventricular WMH (P = 0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD-MCI (P = 0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD-MCI compared with patients in the 1st quintile of periventricular WMH burden (P = 0.004). However, total brain WMH burden was not associated with PD-MCI (P = 0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors. CONCLUSION: Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD.

The Long-Term Impact of Functional Disability on Hospitalization Spending in Singapore.

Singapore is one of the fastest-aging populations due to increased life expectancy and lowered fertility. Lifestyle changes increase the burden of chronic diseases and disability. These have important implications for social protection systems. The goal of this paper is to model future functional disability and healthcare expenditures based on current trends. To project the health, disability and hospitalization spending of future elders, we adapted the Future Elderly Model (FEM) to Singapore. The FEM is a dynamic Markov microsimulation model developed in the US. Our main source of population data was the Singapore Chinese Health Study (SCHS) consisting of 63,000 respondents followed up over three waves from 1993 to 2010. The FEM model enables us to investigate the effects of disability compounded over the lifecycle and hospitalization spending, while adjusting for competing risk of multi-comorbidities. Results indicate that by 2050, 1 in 6 elders in Singapore will have at least one ADL disability and 1 in 3 elders will have at least one IADL disability, an increase from 1 in 12 elders and 1 in 5 elders respectively in 2014. The highest prevalence of functional disability will be in those aged 85 years and above. Lifetime hospitalization spending of elders aged 55 and above is US$24,400 (30.2%) higher among people with functional disability compared to those without disability. Policies that successfully tackle diabetes and promote healthy living may reduce or delay the onset of disability, leading to potential saving. In addition, further technological improvements may reduce the financial burden of disability.

Metabolite-mediated modelling of microbial community dynamics captures emergent behaviour more effectively than species-species modelling.

Personalized models of the gut microbiome are valuable for disease prevention and treatment. For this, one requires a mathematical model that predicts microbial community composition and the emergent behaviour of microbial communities. We seek a modelling strategy that can capture emergent behaviour when built from sets of universal individual interactions. Our investigation reveals that species-metabolite interaction (SMI) modelling is better able to capture emergent behaviour in community composition dynamics than direct species-species modelling. Using publicly available data, we examine the ability of species-species models and species-metabolite models to predict trio growth experiments from the outcomes of pair growth experiments. We compare quadratic species-species interaction models and quadratic SMI models and conclude that only species-metabolite models have the necessary complexity to explain a wide variety of interdependent growth outcomes. We also show that general species-species interaction models cannot match the patterns observed in community growth dynamics, whereas species-metabolite models can. We conclude that species-metabolite modelling will be important in the development of accurate, clinically useful models of microbial communities.

Extreme value analysis of gut microbial alterations in colorectal cancer.

Gut microbes play a key role in colorectal carcinogenesis, yet reaching a consensus on microbial signatures remains a challenge. This is in part due to a reliance on mean value estimates. We present an extreme value analysis for overcoming these limitations. By characterizing a power-law fit to the relative abundances of microbes, we capture the same microbial signatures as more complex meta-analyses. Importantly, we show that our method is robust to the variations inherent in microbial community profiling and point to future directions for developing sensitive, reliable analytical methods.

Non-motor symptoms in early Parkinson's disease with different motor subtypes and their associations with quality of life.

BACKGROUND AND PURPOSE: The aim of this study was to examine non-motor symptoms in different Parkinson's disease (PD) motor subtypes and their associations with quality of life (QoL). METHODS: A total of 132 patients with early PD with comprehensive motor examinations and non-motor symptom assessments were included. Motor subtypes were classified based on Stebbins' method. Non-motor symptoms were assessed by the Non-Motor Symptom Scale (NMSS) and validated by more comprehensive instruments, including the Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). QoL was measured by the Parkinson's Disease Questionnaire-8. RESULTS: We identified 66 patients (50%) with tremor-dominant (TD) subtype, 47 (35.6%) with postural instability and gait disorder (PIGD) subtype and 19 (14.4%) with Intermediate subtype. By comparing NMSS scores, patients with the PIGD subtype had more severe sleep impairment and fatigue (domain 2 score: 5.64 vs. 2.52, P < 0.001), urinary symptoms (domain 7 score: 6.96 vs. 3.48, P = 0.005) and overall more severe non-motor symptoms (NMSS total score: 25.89 vs. 17.27, P = 0.031), compared with patients with the TD subtype. Validation using the PSQI and FSS again suggested that patients with the PIGD subtype had independently and significantly more severe sleep impairment (PSQI score: 5.57 vs. 4.29, P = 0.020) and fatigue (FSS score: 34.81 vs. 25.85, P = 0.003) compared with patients with the TD subtype. Several non-motor symptoms had significant associations with QoL, among which sleep impairment and fatigue (P < 0.0001, partial r2 = 0.273) explained the largest proportion of QoL variability in patients with PD. CONCLUSIONS: Patients with the PIGD subtype had more severe sleep impairment, fatigue and urinary disturbance compared with patients with the TD subtype. Sleep impairment and fatigue were the most important factors affecting QoL independent of motor subtypes. Prompt identification and treatment of these non-motor symptoms may improve patients' QoL.

Comparative evaluation of cDNA library construction approaches for RNA-Seq analysis from low RNA-content human specimens.

With the emergence of RNA sequencing technologies, metatranscriptomic studies are rapidly gaining attention as they simultaneously provide insight into gene expression profiles and therefore disease association pathways of microbial pathogens and their hosts. This approach, therefore, holds promise for applicability in infectious disease diagnostics. A challenge of this approach in the clinical setting is the low amount and quality of RNA, especially microbial RNA in most clinically-infected specimens. Here, we compared two commercially available stranded cDNA library preparation kits, the NuGEN Ovation SoLo RNA-Seq System and the Illumina TruSeq Stranded Total RNA, using RNA extracted from synovial and sonicate fluids from a subject with periprosthetic joint infection. The Ovation SoLo RNA-Seq System provided more useful transcriptomic data for the infecting bacterium, whereas the TruSeq Stranded Total RNA kit provided more useful human transcriptomic data.

Sport, time pressure, and cognitive performance.

Sport participation, fitness, and expertise have been associated with a range of cognitive benefits in a range of populations but both the factors that confer such benefits and the nature of the resulting changes are relatively unclear. Additionally, the interactions between time pressure and cognitive performance for these groups is little studied. Using a flanker task, which measures the ability to selectively process information, and with different time limits for responding, we investigated the differences in performance for participants in (1) an unpredictable, open-skill sport (volleyball), (2) an exercise group engaged in predictable, closed-skill sports (running, swimming), and (3) nonsporting controls. Analysis by means of a drift diffusion analysis of response times was used to characterize the nature of any differences. Volleyball players were more accurate than controls and the exercise group, particularly for shorter time limits for responding, as well as tending to respond more quickly. Drift diffusion model analysis suggested that better performance by the volleyball group was due to factors such as stimulus encoding or motor programming and execution rather than decision making. Trends in the pattern of data seen also suggest less noisy cognitive processing (rather than greater efficiency) and should be further investigated.

Reproducibility of assessing fecal microbiota in chronic constipation.

BACKGROUND: While limited data suggest that the fecal microbiota in healthy people is stable over time, the intraindividual variability of the fecal microbiota in constipated patients is unknown. METHODS: This study evaluated the intraindividual reproducibility of fecal microbiota analyzed with 16S rRNA gene sequencing in two stool samples collected without and after a laxative, respectively, in 25 healthy people and 25 constipated women. Participants completed a food record for 3 d before the stool collection. Colonic transit was measured with scintigraphy. KEY RESULTS: The constipated patients were older (48±15 vs 39±10 y, P=.02) than healthy participants but had a similar BMI. The total daily caloric intake was less (P=.005) in constipated (1265±350 kcal) than healthy participants (1597±402 kcal). Fourteen patients but only two controls (P<.005), had delayed colonic transit. For most measures of alpha (eg, Observed OTU number, Shannon index) and beta diversity (eg, Bray-Curtis dissimilarity, UniFrac, phyla level abundance), the ICCs between two stool samples were high, indicating moderate or strong agreement, and similar in healthy people and constipated patients. The ICC for the weighted UniFrac distance, which is weighted by abundance, was lower than its unweighted counterpart, indicating that the unweighted measure is more robust and reproducible. CONCLUSIONS AND INFERENCES: The intraindividual reproducibility of fecal microbiota in constipated patients is high and comparable to healthy participants. For most purposes, evaluating the fecal microbiota in a single stool sample should generally suffice in adequately powered studies of healthy and constipated patients.

Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation.

BACKGROUND: Differences in the gut microbiota and breath methane production have been observed in chronic constipation, but the relationship between colonic microbiota, transit, and breath tests remains unclear. METHODS: In 25 healthy and 25 constipated females we evaluated the sigmoid colonic mucosal and fecal microbiota using 16S rRNA gene sequencing, abundance of hydrogenogenic FeFe (FeFe-hydA) and hydrogenotrophic (methyl coenzyme M reductase A [mrcA] and dissimilatory sulfite reductase A [dsrA]) genes with real-time qPCR assays, breath hydrogen and methane levels after oral lactulose, and colonic transit with scintigraphy. KEY RESULTS: Breath hydrogen and methane were not correlated with constipation, slow colon transit, or with abundance of corresponding genes. After adjusting for colonic transit, the abundance of FeFehydA, dsrA, and mcrA were greater (P<.005) in colonic mucosa, but not stool, of constipated patients. The abundance of the selected functional gene targets also correlated with that of selected taxa. The colonic mucosal abundance of FeFe-hydA, but not mcrA, correlated positively (P<.05) with breath methane production, slow colonic transit, and overall microbiome composition. In the colonic mucosa and feces, the abundance of hydrogenogenic and hydrogenotrophic genes were positively correlated (P<.05). Breath methane production was not associated with constipation or colonic transit. CONCLUSIONS & INFERENCES: Corroborating our earlier findings with 16S rRNA genes, colonic mucosal but not fecal hydrogenogenic and hydrogenotrophic genes were more abundant in constipated vs. healthy subjects independent of colonic transit. Breath gases do not directly reflect the abundance of target genes contributing to their production.

Molecular classification of gastric cancer.

Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future.

A national common massive transfusion protocol (MTP) is a feasible and advantageous option for centralized blood services and hospitals.

BACKGROUND: A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals. METHODS: Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood-derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non-trauma general medical, surgical and obstetric patients. RESULTS: There were 434 activations of the MTP from October 2011 to October 2013. Thirty-nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra-operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri-partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood-derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation. CONCLUSION: This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider.

Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2) ): an evidence-based mnemonic for the treatment of systolic heart failure.

Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline-based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice, which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID (2) , standing for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine, devices (automatic implantable cardioverter defibrillator, cardiac resynchronisation therapy or both) and digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence-based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition.

High-resolution SNP microarray investigation of copy number variations on chromosome 18 in a control cohort.

Copy number variations (CNVs) as described in the healthy population are purported to contribute significantly to genetic heterogeneity. Recent studies have described CNVs using lymphoblastoid cell lines or by application of specifically developed algorithms to interrogate previously described data. However, the full extent of CNVs remains unclear. Using high-density SNP array, we have undertaken a comprehensive investigation of chromosome 18 for CNV discovery and characterisation of distribution and association with chromosome architecture. We identified 399 CNVs, of which loss represents 98%, 58% are less than 2.5 kb in size and 71% are intergenic. Intronic deletions account for the majority of copy number changes with gene involvement. Furthermore, one-third of CNVs do not have putative breakpoints within repetitive sequences. We conclude that replicative processes, mediated either by repetitive elements or microhomology, account for the majority of CNVs in the healthy population. Genomic instability involving the formation of a non-B structure is demonstrated in one region.

The impact of clinical protocols in the management of severe sepsis: a prospective cohort study.

This study aimed to assess the availability of clinical protocols and their effect on compliance to the Surviving Sepsis Campaign bundles and on mortality in severe sepsis in ten Singaporean adult teaching intensive care units (ICU). The presence of 11 protocols in the ICUs, steps taken based on the Johns Hopkins University Quality and Safety Research Group's model to translate protocols into practice, and organisational characteristics were assessed. Clinical and research personnel recorded characteristics of patients with severe sepsis who were admitted in July 2009, the achievement of sepsis bundle targets and outcomes. Hospital mortality was 39% for 128 patients. Fewer than half of the ICUs had protocols for early goal-directed therapy, blood cultures, antibiotics, steroids, lung-protective ventilation and weaning. Compliance rates with the resuscitation and management bundles were 18 and 3% respectively. Units with protocols were generally not more likely to achieve associated bundle targets. Steps from the Johns Hopkins model to measure performance, engage teams and sustain and extend interventions were taken in fewer than half of the available protocols. However, on logistic regression analysis, the number of protocols available per ICU was independently and inversely associated with mortality. In conclusion, clinical protocols are infrequently available in Singapore's ICUs and when present do not generally improve compliance to the sepsis bundles. These protocols may, however, be a surrogate marker of the quality of care as they are independently associated with decreased mortality. The use of an integrated and multifaceted approach to translate protocols into practice should be considered.

Accuracy of ProSeal™ laryngeal mask airway intracuff pressure estimation using finger palpation technique - a prospective, observational study.

The incidence of pharyngolaryngeal adverse events associated with laryngeal mask airways can be reduced by the use of manometry to limit the laryngeal mask airway intracuff pressures. We conducted a prospective, observational study in 80 patients undergoing general anaesthesia with the ProSeal™ laryngeal mask airway to determine the accuracy of a finger palpation technique compared to actual readings obtained from a hand-held manometer by different anaesthesia personnel. The strength of association of estimated versus actual intracuff pressures, R, for nurse anaesthesia assistants, junior anaesthetists and senior anaesthetists were 0.21 (weak), 0.35 (moderate) and 0.78 (strong) respectively. Subgroup analysis showed that anaesthetists with more than three years of experience were more accurate than those with less than three years of experience. The actual versus estimated intracuff pressures were 4±17 vs 19±27 cmH2O (P value <0.001) respectively. In all groups, the palpation technique tended to underestimate the actual intracuff pressure by a mean of 10.3 cmH2O. Palpation accuracy decreased when actual intracuff pressures were >80 cmH2O. These findings suggest that cuff pressure manometry should be recommended as standard of care with the use of laryngeal mask airways.

Perioperative risk factors in obese patients for bariatric surgery: a Singapore experience.

INTRODUCTION: Morbid obesity and obstructive sleep apnoea (OSA) are increasingly encountered in anaesthetic practice today. Difficult intubation may be seen more frequently in our practice. This high-risk group may also be more prone to complications in the postoperative period. METHODS: We reviewed a consecutive series of patients who had undergone laparoscopic gastric banding at our institution from 2001 to 2006. The incidence of difficult intubation, early postoperative complications and its attendant risk factors were studied. RESULTS: Severe OSA and neck circumference greater than 44 cm were factors associated with difficult intubation in morbidly obese patients who presented for bariatric surgery. Asthma and increasing age may be associated risk factors for adverse events in the postoperative period. CONCLUSION: It is important to anticipate and prepare for a difficult intubation scenario in patients with severe OSA and a larger neck circumference. Close monitoring is recommended for patients with respiratory comorbidities and advanced age.