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Background Community-acquired pneumonia (CAP) is one of the most common infectious diseases and is a significant cause of mortality and morbidity globally. A microbial cause was not determined in a sizable percentage of patients with CAP; there are increasing data to suggest regional differences in bacterial aetiology. We devised a multiplex real-time PCR assay for detecting four microorganisms (Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and Burkholderia pseudomallei) of relevance to CAP infections in Asia. Methods Analytical validation was accomplished using bacterial isolates (n=10–33 of each target organism for analytical sensitivity and n=117 for analytical sensitivity) and clinical validation using 58 culture-positive respiratory tract specimens. Results The qPCR assay exhibited 100% analytical sensitivity and analytical specificity, and 100% clinical sensitivity and 94–100% clinical specificity. The limit of detection and efficiency for the multiplex PCR assay were 3–33 CFU/mL and 93–110%, respectively. The results showed that the PCR-based method had higher sensitivity than traditional culture-based methods. The assay also demonstrated an ability to semiquantify bacterial loads. Conclusion We have devised a reliable laboratory-developed multiplex qPCR assay, with a turnaround time of within one working day, for detection of four clinically important CAP-associated microorganisms in Asia. The availability of a test with improved diagnostic capabilities potentially leads to an informed choice of antibiotic usage and appropriate management of the patient to achieve a better treatment outcome and financial savings.

Prolonged surgery is a known risk of pressure ulcer formation. Pressure ulcers affect the quality of life, are a significant cause of morbidity and mortality, and pose a burden on the healthcare system. This study aimed to compare the effectiveness of an alternating pressure (AP) overlay with Gel pad against the Gel pad in reducing interface pressure (IP) during prolonged surgery.A total of 180 participants from a tertiary hospital were randomized to AP overlay with Gel pad group (n = 90) and Gel pad group (n = 90). Patients were placed supine on the pressure redistributing surfaces, and IP data under the sacrum and ischial tuberosities were collected at an interval of 30 min from 0 min up to a maximum of 570 min.Based on data from 133 participants, the average IPs during all the deflation cycles of the AP overlay (with Gel pad) were significantly lower than the average continuous IP recorded for Gel pad throughout the measuring period (p 0.001). Only three patients (2.26% of study participants) - Gel pad group (n = 2; 2.99%) and AP overlay with Gel pad group (n = 1; 1.52%) developed post-operative pressure ulcer (p = 0.5687).The lower IP during deflation cycles of the AP overlay (with Gel pad) suggests its potential effectiveness in preventing pressure ulcer formation in patients undergoing prolonged surgery. The prevention and reduction of pressure ulcers will have a considerable impact on the improved quality of life and cost savings for the patient. The study findings may facilitate the formulation of policies for preventing pressure ulcer development in the perioperative setting.

Purpose Education in airway management is a fundamental component of anesthesiology training programs. There has been a shift towards the use of simulation models of higher fidelity for education in airway management. The goal of this study was to create a novel cadaveric model of a simulated parapharyngeal abscess with features of a difficult airway such as distorted anatomy and narrow airway passages presenting as stridor. The model was further assessed for its suitability for enhanced experiential learning in the management of difficult airways. Methods Cadaver heads were modified surgically to simulate parapharyngeal abscess. Airtight torso of the cadaver was connected to an Oxylog ventilator to simulate respiratory movements—the opening and closing of air channels with breaths in a patient with parapharyngeal abscess. Advanced airway workshop facilitators conducted directed one-to-one learning, and provided feedback to participants. A paper-based feedback was obtained from 72 participants on their confidence level, and the realism, attractiveness, beneficial, and difficulty levels of the simulated cadaveric models. Results The modified cadavers were reliable in simulating difficult airways. The majority of participants (91%) reported an increase in confidence level for management of the difficult airway after the experience with the modified cadavers and found the models realistic (93%), attractive (92%), beneficial (93%), and difficult (85%). Conclusions Surgical modifications of cadavers to simulate difficult airways such as parapharyngeal abscess with edema and stridor can be incorporated into advanced airway management courses to enhance experiential learning in airway management by awake fibreoptic intubation, and promote patient safety. Supplementary Information The online version contains supplementary material available at 10.1007/s00540-021-02904-0.

Introduction Failure of airway management remains a significant source of morbidity and mortality. Advanced airway management has been addressed effectively by simulation-based training. However, simulation of difficult airways in manikins is limited by the pre-set conditions provided by the manufacturer. Life-like conditions in the form of the softness of the tissue and true anatomy as seen in cadaver models are needed to create simulated models with a closer resemblance to real patients. The goal of this study was to determine the feasibility of simulating difficult airway from submandibular abscess in cadaver models by surgical modification of the cadaver heads for use in enhanced experiential learning of the management of difficult airways. Methods The cadaver heads were modified surgically to simulate a submandibular abscess. The models were used in an airway course where participants provided feedback on the realistic nature of the model and its benefits for difficult airway training. The ease of tracheal intubation of the models with the assistance of video laryngoscopy was assessed. Results The modified cadavers were acceptable in simulating difficult airway as demonstrated by the feedback from the participants. All participants (100% [95% confidence interval = 89.1%-100%]) found the models to be realistic and beneficial for difficult airway training. A good proportion (56.3%) felt that the intubation technique was made easier with the video laryngoscopy. Conclusions Cadavers can be modified to simulate pathologies associated with difficult airways. These models can be used to enhance experiential learning and the management of difficult airways.

Background: Breast cancer is the top cancer suffered by women worldwide and has been identified to be the greatest killer for women living in Singapore. Unfortunately, most of breast cancer cases were detected only at later stage of disease development. This has crippled the effort of breast cancer therapy. As early detection of breast cancer could greatly improve the outcome of breast cancer therapy, it is of utmost importance to identify relevant biomarkers at the primitive stage of breast cancer development before the transformation of normal breast cells into cancerous cells. These biomarkers provide important clues leading to an efficient and targeted treatment approach in breast cancer preventive care.Methods: 455 breast cancer patients were consented to join this study. Buccal swabs were collected for genotyping on CYP2B6*6, CYP2C19 *2 & CYP2C19*3. The genotyping data were then compared to data collected from healthy individuals. Clinical data were collected from patient notes and analysed. All the statistical analyses were done using SPSS statistical software, version 19.0. Chi-square or Fisher’s Exact test were performed to examine the difference between subject’s characteristics for categorical variables and One-Way Anova was performed to assess age difference across alleles of CYP2B6*6, CYP2C19*2 and CYP2C19*3. Binary logistics regression was performed to identify demographic factors associated with breast cancer.Results: We reported thatCYP2B6*6 could be a risk factor leading to earlier onset of breast cancer among Indian population with OR found to be 1.69 (95% C.I.= 0.549-5.191, p=0.359). In the case of CYP2C19*2, OR is 1.57 for Malay (95% C.I. = 0.696-3.522, p=0.278); 1.15 for Chinese population (95% C.I. =0.862-1.545, p=0.335) and 1.03 for Indian (95% C.I. =0.301-3.496, p=0.968). CYP2C19*3 OR in Chinese population is 1.34 (95% C.I. =0.830-2.155, p=0.231) and 0.77 (95% C.I. =0.172-3.394, p=0.724) for Malay population. No CYP2C19*3 was detected in both cohorts of Indian patients and healthy controls. Conclusions: CYP2B6*6 and CYP2C19*2 polymorphisms may confer a risk for breast cancer development in Singaporean breast cancer patients. This is an exploratory study to identify potential breast cancer susceptibility gene polymorphisms, a bigger sample size study could be done to corroborate these findings in future studies.

Background: Healthcare education models have recently shifted from the traditional reliance on the apprenticeship model, where trainees learn on real patients in actual clinical settings, to one based on simulation models. Education in airway management is a fundamental component of anesthetic training programs, and airway modification to simulate difficult airways increases the fidelity of airway management training. Objective: The study goal was to determine the feasibility of simulating difficult airways such as mandibular fracture and post-tonsillectomy bleed in cadaver models by surgical modification for the use in enhanced experiential learning of difficult airway management. Methods: Two cadaver heads were modified surgically to simulate a mandibular fracture and post-tonsillectomy bleed. Workshop facilitators conducted directed one-to-one learning and provided feedback to participants. A paper-based feedback was obtained from the participants on their confidence level, and the realism, attractiveness, beneficial levels, and difficulty levels of the simulation models used. Results: The modified cadavers were reliable in simulating difficult airways. The majority of participants (83.3% for fractured mandible and 87.1% for post-tonsillectomy bleed) reported an increase in confidence level for management of the difficult airway after the experience with the modified cadavers, and found both models realistic, attractive, and beneficial for difficult airway training. Conclusions: Surgical modifications of cadavers to simulate difficult airways such as fractured mandible and post-tonsillectomy bleed may be incorporated into advanced airway management courses to enhance experiential learning.

Background and Aim Perturbance in the composition of human gut microbiota has been associated with metabolic disorders such as obesity, diabetes mellitus, and insulin resistance. The objectives of this study are to examine the effects of ethnicity, central obesity, and recorded dietary components on potentially influencing the human gut microbiome. We hypothesize that these factors have an influence on the composition of the gut microbiome. Methods Subjects of Chinese (n = 14), Malay (n = 10), and Indian (n = 11) ancestry, with a median age of 39 years (range: 22–70 years old), provided stool samples for gut microbiome profiling using 16S rRNA sequencing and completed a dietary questionnaire. The serum samples were assayed for a panel of biomarkers (interleukin‐6, tumor necrosis factor alpha, adiponectin, cleaved cytokeratin 18, lipopolysaccharide‐binding protein, and limulus amebocyte lysate). Central obesity was defined by waist circumference cut‐off values for Asians. Results There were no significant differences in Shannon alpha diversity for ethnicity and central obesity and no associations between levels of inflammatory cytokines and obesity. The relative abundances of Anaerofilum (P = 0.02), Gemellaceae (P = 0.02), Streptococcaceae (P = 0.03), and Rikenellaceae (P = 0.04) were significantly lower in the obese group. From principle coordinate analysis, the effects of the intake of fiber and fat/saturated fat were in contrast with each other, with clustering of obese individuals leaning toward fiber. Conclusion The study demonstrated that there were differences in the gut microbiome in obese individuals. Certain bacterial taxa were present in lower abundance in the group with central obesity. Fiber and fat/saturated fat diets were not the key determinants of central obesity., The objectives of this study are to examine the effects of ethnicity, central obesity, and dietary components on the human gut microbiome. Asian subjects (n = 35) provided stool samples for gut microbiome profiling using 16S rRNA sequencing and completed a dietary questionnaire. The relative abundances of Anaerofilum (P = 0.02), Gemellaceae (P = 0.02), Streptococcaceae (P = 0.03), and Rikenellaceae (P = 0.04) were significantly lower in the obese group.

Highlights • Performance of FilmArray, AnyplexII, and Argene platforms was comparable. • Nasopharyngeal swabs in UTM and endotracheal aspirates are suitable sample types. • Test volume is the main determinant for the selection of platform. • FilmArray is most automated, of lowest-throughput and has highest reagent cost., Background Respiratory infections are common reasons for hospital admission, and are associated with enormous economic burden due to significant morbidity and mortality. The wide spectrum of microbial agents underlying the pathology renders the diagnosis of respiratory infections challenging. Molecular diagnostics offer an advantage to the current serological and culture-based methods in terms of sensitivity, coverage, hands-on time, and time to results. Objectives This study aimed to compare the clinical performance of three commercial kits for respiratory viral detection. Study design The performance of FilmArray Respiratory Panel, AnyplexII RV16, and Argene was compared using clinical respiratory samples (n = 224, comprising 189 nasopharyngeal swabs in Universal Transport Medium (UTM) and 35 endotracheal aspirates), based on common overlapping targets across the platforms. Influenza A “equivocal” and “no-subtype” samples by FilmArray were further compared to a laboratory-developed Influenza A/B test. Results and Conclusions The overall performance of all three platforms appeared to be comparable with regards to sensitivities (95.8–97.9%) and specificities (96.1–98.0%), detection of coinfections, and distinguishment of influenza from non-influenza cases. “Equivocal” and “no-subtype” samples by FilmArray mostly represented weak Influenza A by laboratory-developed test. Lower respiratory tract samples had comparable final-run success-rates and discordant-rates as compared to UTM. Coronavirus HKU1, which was not targeted by AnyplexII RV16, were detected as OC43. The expected test volume would be the main determinant for the selection of platform. Among the platforms, the FilmArray is the most automated but is of the lowest-throughput and has the highest reagent cost.

Introduction The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome. Methods Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses. Results The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively. Conclusion The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.

Given increasing antimicrobial resistance, we aimed to determine antibiotic susceptibility and presence of resistance genes in uropathogens in primary care, factors associated with resistance to commonly prescribed antibiotics, and effect of treatment on early symptom resolution. We conducted a prospective study of primary care patients with urinary tract infection (UTI) symptoms and culture-confirmed UTI in Singapore from 2015 to 2016., Given increasing antimicrobial resistance, we aimed to determine antibiotic susceptibility and presence of resistance genes in uropathogens in primary care, factors associated with resistance to commonly prescribed antibiotics, and effect of treatment on early symptom resolution. We conducted a prospective study of primary care patients with urinary tract infection (UTI) symptoms and culture-confirmed UTI in Singapore from 2015 to 2016. Cohort characteristics and antimicrobial susceptibility of cultured isolates were analyzed. Among Enterobacteriaceae isolates, early symptom resolution (within 3 days) according to antibiotic prescribed and isolate susceptibility and factors associated with antibiotic resistance were evaluated. Of 695 symptomatic patients, 299 were urine culture positive; of these 299 patients, 259 (87%) were female. Escherichia coli was the most common uropathogen (76%). Enterobacteriaceae isolates (n = 283) were highly susceptible to amoxicillin-clavulanate (86%), nitrofurantoin (87%), and fosfomycin (98%), but >20% were resistant to ciprofloxacin and co-trimoxazole. Isolates resistant to appropriate indicator antibiotics were further tested to determine proportions positive for blaCTX-M (14/26, 54%), plasmid-mediated ampC (12/24, 50%), qnr (7/69, 10%), and fos (1/6, 17%) resistance genes. A total of 67% of patients given antibiotics with susceptible isolates reported early resolution versus 45% given antibiotics with nonsusceptible isolates (P = 0.001) and 27% not treated (P = 0.018). On multivariable analysis, Indian ethnicity and diabetes mellitus were associated with amoxicillin-clavulanate resistance. Genitourinary abnormalities, UTI in the past 12 months, and hospitalization in the past 6 months were associated with ciprofloxacin and co-trimoxazole resistance. Patients given active empirical antibiotics were most likely to report early symptom resolution, but correlation with in vitro susceptibility was imperfect. Factors associated with resistance may guide the decision to obtain initial urine culture.

BACKGROUND & AIMS We compared the effects of weight loss induced with the glucagon-like peptide-1 agonist liraglutide, with that of lifestyle modification, followed by weight maintenance after discontinuing intervention, in obese adults with non-alcoholic fatty liver disease (NAFLD). METHODS Thirty obese (mean age 40.7 ± 9.1 years, BMI 33.2 ± 3.6 kg/m2 , 90% male) adults with NAFLD defined as liver fat fraction (LFF) > 5% on magnetic resonance imaging without other causes of hepatic steatosis were randomized to a supervised programme of energy restriction plus moderate-intensity exercise to induce ≥ 5% weight loss (DE group, n = 15), or liraglutide 3 mg daily (LI group, n = 15) for 26 weeks, followed by 26 weeks with only advice to prevent weight regain. RESULTS Diet and exercise and LI groups had significant (P

Background Brugada syndrome (BrS) is an inherited primary arrhythmia disorder leading to sudden cardiac arrest. SCN 5A , encoding the α‐subunit of the cardiac sodium channel (Nav1.5), is the most common pathogenic gene of BrS. An implantable cardioverter defibrillator ( ICD ) is the standard treatment for secondary prevention. This study aimed to evaluate association of the SCN 5A variant with this cardiac conduction disturbance and appropriate ICD shock therapy in Thai symptomatic BrS patients with ICD implants. Methods and Results Symptomatic BrS patients diagnosed at university hospital were enrolled from 2008 to 2011. The primary outcome of the study was an appropriate ICD shock defined as having non‐pacing‐associated ICD shock after the occurrence of ventricular tachycardia or ventricular fibrillation. Associations between SCN 5A polymorphisms, cardiac conduction disturbance, and potential confounding factors associated with appropriate ICD shock therapy were analyzed. All 40 symptomatic BrS patients (median age, 43 years) with ICD implantations were followed for 24 months. There were 16 patients (40%) who had the appropriate ICD shock therapy after ICD treatment. An independent factor associated with appropriate ICD shock therapy was SCN 5A‐ R1193Q with an adjusted hazard ratio of 10.550 (95% CI , 1.631–68.232). Conclusions SCN 5A‐ R1193Q is associated with cardiac conduction disturbances. It may be a genetic marker associated with ventricular arrhythmia leading to appropriate ICD shock therapy in symptomatic BrS patients with ICD treatment. Because of the small sample size of study population and the appropriate ICD shock outcome, further large studies are needed to confirm the results of this study.

1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.