Search

BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). INTERPRETATION: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. FUNDING: National Institutes of Health.

Background. Herein, we purposed to establish a nomogram model capable of assessing the probability of in-hospital survival in patients with multiple trauma. Methods. Our retrospective study is associated with 286 multiple trauma patients with 21 variables from 2017 to 2021 in The Second Affiliated Hospital, Hengyang Medical School, University of South China. We performed the univariate and multivariate logistic regression analyses for investigating the risk factors of multiple trauma. Further, we constructed a novel nomogram model, and this nomogram was evaluated by a calibration plot. Based on the multivariate analysis or the nomogram prediction model, we calculated the risk score of each patient for multiple trauma. Moreover, we compared the survival probability between the high-risk score and low-risk score groups. Finally, we assessed the discrimination of the risk score by using the C-index and the time-dependent receiver operating characteristics (ROC) curve. Results. Multivariate regression analysis revealed that the age and ISS scores were the independent risk factors, while the GCS score had protective effects on in-hospital survival. The high C-index and area under the curve (AUC) of the ROC curve confirmed reasonable discrimination for the multivariate analysis and the nomogram prediction model. Further, the calibration plot indicated reasonable accuracy of the nomogram predicting 30-day and 60-day survival probabilities. Conclusion. The nomogram model established here has good predictive efficacy for in-hospital survival of patients with multiple injuries.

101BHG-D01 nasal spray is the first novel long-acting cholinergic M receptor antagonist under development to treat rhinorrhea in rhinitis. This first-in-human study aimed to evaluate the safety, tolerability, and pharmacokinetics of 101BHG-D01 nasal spray following single intranasal doses in healthy Chinese subjects.A randomized, double-blind, placebo-controlled, single-dose escalation study was conducted in healthy Chinese volunteers after intranasal doses of 101BHG-D01 nasal spray or placebo ranging from 40 µg to 960 µg (total of six doses). Blood samples were collected at scheduled time points, and plasma concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUCFollowing single intranasal dosing, 101BHG-D01 was rapidly absorbed with a median T101BHG-D01 nasal spray was safe and well tolerated in healthy Chinese subjects when administered intranasally in single escalating doses. The mean C

Background Large-scale quarantine facilities staffed with non-healthcare workers (NHCW) were instrumental in preventing community spread of COVID-19 (coronavirus disease of 2019). The objective of this study was to determine the effectiveness of a newly developed procedural skills training framework in ensuring personal protective equipment (PPE) compliance of PPE-naïve NHCWs. Materials and methods We developed a PPE procedural skills training framework for NHCWs using the Learn, See, Practice, Prove, Do, and Maintain (LSPPDM) framework and international guidelines on PPE for healthcare workers. The NHCWs underwent PPE training using this framework, conducted by a team of Infection Prevention nurses, prior to being stationed within the CCF. Effectiveness of the LSPPDM PPE training framework was assessed using: 1) competency assessment scores for NHCWs, 2) PPE compliance rates from daily audit findings, and, 3) healthcare-associated COVID-19 infection rates of NHCWs. Results A total of 883 NHCWs had completed the PPE training and demonstrated competency in PPE compliance, fulfilling 100% of the checklist requirements. Mean PPE compliance of all NHCWs during the 11-week study period was noted to be >96%. The post-implementation improvement was statistically significant when the compliance was expressed in 3-days blocks) and in bed management staff (P = < 0.05). None of the 883 NHCWs who underwent PPE training via the LSPPDM framework were diagnosed with healthcare-associated COVID-19 infection. Conclusions An evidence-based skills training framework is effective in PPE training of large numbers of NHCWs, resulting in high compliance of appropriate PPE use and prevention of healthcare-associated COVID-19 infection.

Introduction: In Singapore, non-anaesthesiologists generally administer sedation during gastrointestinal endoscopy. The drugs used for sedation in hospital endoscopy centres now include propofol in addition to benzodiazepines and opiates. The requirements for peri-procedural monitoring and discharge protocols have also evolved. There is a need to develop an evidence-based clinical guideline on the safe and effective use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting. Methods: The Academy of Medicine, Singapore appointed an expert workgroup comprising 18 gastroenterologists, general surgeons and anaesthesiologists to develop guidelines on the use of sedation during gastrointestinal endoscopy. The workgroup formulated clinical questions related to different aspects of endoscopic sedation, conducted a relevant literature search, adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and developed recommendations by consensus using a modified Delphi process. Results: The workgroup made 16 recommendations encompassing 7 areas: (1) purpose of sedation, benefits and disadvantages of sedation during gastrointestinal endoscopy; (2) pre-procedural assessment, preparation and consent taking for sedation; (3) Efficacy and safety of drugs used in sedation; (4) the role of anaesthesiologist-administered sedation during gastrointestinal endoscopy; (5) performance of sedation; (6) post-sedation care and discharge after sedation; and (7) training in sedation for gastrointestinal endoscopy for non-anaesthesiologists. Conclusion: These recommendations serve to guide clinical practice during sedation for gastrointestinal endoscopy by non-anaesthesiologists in the hospital setting. Keywords: Benzodiazepines, gastrointestinal endoscopy opiates, propofol, sedation

Background Without sufficient evidence in postoperative acute kidney injury (AKI) in critically ill patients undergoing emergency surgery, it is meaningful to explore the incidence, risk factors, and prognosis of postoperative AKI. Methods A prospective observational study was conducted in the general intensive care units (ICUs) from January 2014 to March 2018. Variables about preoperation, intraoperation and postoperation were collected. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. Results Among 383 critically ill patients undergoing emergency surgery, 151 (39.4%) patients developed postoperative AKI. Postoperative reoperation, postoperative Acute Physiology and Chronic Health Evaluation (APACHE II) score, and postoperative serum lactic acid (LAC) were independent risk factors for postoperative AKI, with the adjusted odds ratio (ORadj) of 1.854 (95% confidence interval [CI], 1.091–3.152), 1.059 (95%CI, 1.018–1.102), and 1.239 (95%CI, 1.047–1.467), respectively. Compared with the non-AKI group, duration of mechanical ventilation, renal replacement therapy, ICU and hospital mortality, ICU and hospital length of stay, total ICU and hospital costs were higher in the AKI group. Conclusions Postoperative reoperation, postoperative APACHE II score, and postoperative LAC were independent risk factors of postoperative AKI in critically ill patients undergoing emergency surgery.

Purpose Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. Methods The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. Results The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. Conclusion These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.

Aim We performed a systematic review and meta-analysis to examine the accuracy and safety of using the electrocardiogram (ECG) positioning technique to localize the peripherally inserted central catheter (PICC) tip position to provide objective evidence for its clinical application. Methods We searched the literature for randomized controlled trials evaluating the diagnostic analysis of using electrocardiograms to localize PICC tip positions in the MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO databases. We used a risk ratio with accompanying 95% confidence interval (CI) to express estimates. Reviewer Manager (RevMan) 5.1.0 was used to complete all statistical analyses. Results This systematic review identified 9 studies (N = 3,194 patients). Overall, the results of the meta-analysis revealed that, for patients in whom the ECG positioning method was used compared with patients in whom the landmark positioning method was used, the RR for accurate catheter tip positioning was RR = 1.17, and the difference was statistically significant. The RR for the incidence of complications was RR = 0.28, and the difference was statistically significant. Conclusions The application of ECGs in PICC tip positioning can improve the accuracy of catheter tip positioning and reduce the incidence of related complications.

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.

Purpose This study aims to compare the effects of ticagrelor and clopidogrel on platelet function, cardiovascular prognosis, and bleeding in patients with unstable angina pectoris. Methods Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) were enrolled (January 2018–December 2019). In total, 212 patients were treated with ticagrelor (90 mg twice daily) and 210 patients were treated with clopidogrel (75 mg once daily). Thromboelastography and light transmission aggregometry were used to measure the platelet aggregation rate (PAR). High-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), and heart-type fatty acid–binding protein (h-FABP) were measured to assess myocardial injury after PCI. Cardiovascular prognosis and bleeding events were evaluated in hospital and 12 months after discharge. Results The PAR was significantly slower with ticagrelor (P P P P P P Conclusion Ticagrelor was more effective in suppressing the PAR than clopidogrel and reduced PCI-induced myocardial injury in patients with unstable angina pectoris. However, it increased in-hospital and 12-month bleeding events and had no benefit on in-hospital and 12-month MACEs.

OBJECTIVE: To evaluate the compatibility of Tianma (Rhizoma Gastrodiae, TM), Yanlingcao (Trillium tschonoskii Maxim, YLC) and Bingpian (Borneolum Syntheticum, BP), and their efficacy in the treatment of cerebral ischemic stroke. METHODS: Network pharmacology was used to determine the compatibility of TM, YLC, and BP, and their potential mechanism. The middle cerebral artery occlusion (MCAO) rat model was used to evaluate the curative effect of the six combinations of TM, YLC, and BP (TZB1-TZB6) on cerebral ischemia, by using the weight matching method to form. The potential component changes of TM and YLC in the blood and brains of rats were analyzed using ultra performance liquid chromatography-mass spectrometry. Finally, molecular docking linked the results of animal experiments and network pharmacology, determining the potential component contributors of TM and YLC to treating ischemic stroke. RESULTS: TZB reduced the cerebral infarct volume and protected the nerve cells in MCAO rats. The components of TM and YLC were also identified in the blood and brain homogenate, and BP can facilitate the entry of the components of TM and YLC into the blood and brain. Diosgenin, pennogenin, and gastrodin induced effective binding activities with adenosine receptor a1. CONCLUSION: We investigate an approach that improves the means of folk prescription combined with multi technology that maybe promote the transformation of Chinese medicinal prescription into component-based Chinese medicine.

The level of circulating tumor cells (CTCs) in blood is a predictor of metastatic cancer progress, serving as an important biomarker for cancer diagnosis, prognosis, and therapy. Currently, there are mainly two conventional strategies to distinguish CTCs, including biological property-based affinity capture and physical property-based label-free isolation. Although great progress has been made in this field, the ability to distinguish CTCs still needs to be improved further due to the cell heterogeneity. Herein, a metabolism-based isolation approach was applied to identify tumor cells according to the "Warburg effect", and a bifunctional open-space platform with fluid walls was developed for real-time monitoring and in situ capture/analysis of tumor cells. A drop-on-demand inkjet printing technique was introduced to create a single cell-containing droplet array with high throughput and high encapsulation rate, and the homogeneous crystalline matrix spots ejected from the inkjet also provided high-quality and reproducible lipid profiling. This platform could combine both microscopic image and mass data, and it has been proven to be capable of isolating and identifying CTCs in complex blood samples, making it a promising tool for evaluating the efficacy of therapy and monitoring the disease progression.

Highlights • The impact of a multimodal infection control strategy originally designed for containment of COVID-19 on the rates of other hospital-acquired-infections (HAIs) was evaluated over a 7-month period across the largest healthcare system in Singapore. • During the COVID-19 pandemic, methicillin-resistant Staphylococcus aureus acquisition rates declined significantly, together with central-line-associated-bloodstream infection rates; likely due to increased compliance with standard precautions. • Enhanced infection control measures resulted in the unintended positive consequences of containing health care-associated respiratory viral infections, with a significant and sustained decline for both enveloped and nonenveloped respiratory viruses. • The ongoing COVID-19 pandemic provided the impetus to demonstrate the potential benefit of heightened infection control measures in controlling HAIs and acquisition of multidrug-resistant-organisms., Background In the current COVID-19 pandemic, aggressive Infection Prevention and Control (IPC) measures have been adopted to prevent health care-associated transmission of COVID-19. We evaluated the impact of a multimodal IPC strategy originally designed for the containment of COVID-19 on the rates of other hospital-acquired-infections (HAIs). Methodology From February-August 2020, a multimodal IPC strategy was implemented across a large health care campus in Singapore, comprising improved segregation of patients with respiratory symptoms, universal masking and heightened adherence to Standard Precautions. The following rates of HAI were compared pre- and postpandemic: health care-associated respiratory-viral-infection (HA-RVI), methicillin-resistant Staphylococcus aureus, and CP-CRE acquisition rates, health care-facility-associated C difficile infections and device-associated HAIs. Results Enhanced IPC measures introduced to contain COVID-19 had the unintended positive consequence of containing HA-RVI. The cumulative incidence of HA-RVI decreased from 9.69 cases per 10,000 patient-days to 0.83 cases per 10,000 patient-days (incidence-rate-ratio = 0.08; 95% confidence interval [CI] = 0.05-0.13, P< .05). Hospital-wide MRSA acquisition rates declined significantly during the pandemic (incidence-rate-ratio = 0.54, 95% CI = 0.46-0.64, P< .05), together with central-line-associated-bloodstream infection rates (incidence-rate-ratio = 0.24, 95% CI = 0.07-0.57, P< .05); likely due to increased compliance with Standard Precautions. Despite the disruption caused by the pandemic, there was no increase in CP-CRE acquisition, and rates of other HAIs remained stable. Conclusions Multimodal IPC strategies can be implemented at scale to successfully mitigate health care-associated transmission of RVIs. Good adherence to personal-protective-equipment and hand hygiene kept other HAI rates stable even during an ongoing pandemic where respiratory infections were prioritized for interventions.

Context Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. Objective To observe the clinical safety and tolerability of CALAS. Materials and methods Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Results Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). Discussion and conclusions CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

Endothelial cell is one critical structure of blood vessels, and irregular migration and proliferation of endothelial cell might cause progression of several vascular diseases such as atherosclerosis and restenosis. We showed that TNF-α, PDGF-bb, and IL-1β promote RNCR3 expression in a dose-dependent manner inhuman endothelial cell. RNCR3 level is higher in serum of atherosclerosis patients compared with those in control volunteers. Overexpression of RNCR3 promotes cell proliferation and three inflammatory cytokine secretion including IL-6, IL-1β, and TNF-α in endothelial cell. We illustrated that overexpression of RNCR3 inhibits miR-185-5p expression in endothelial cell. Furthermore, we indicated that miR-185-5p level is lower in the serum of patients with atherosclerosis compared with those in control volunteers. There is a negative correlation between miR-185-5p and RNCR3 expression in serum of patients with atherosclerosis. Using Targetscan, it predicted that miR-185-5p may bind to cyclin D2 and miR-185-5p is one potential target of miR-185-5p. Luciferase reporter data indicated that miR-185-5p suppresses luciferase value of wild-type cyclin D2 while it has no influence of cyclin D2 mutant. Overexpression of RNCR3 enhances cyclin D2 expression in endothelial cell. Moreover, RNCR3 induces cell growth and enhances inflammatory cytokine secretion through modulating cyclin D2 expression in endothelial cell. These results suggested that RNCR3 may serve as one new target for the treatment of atherosclerosis.

Objectives To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers. Methods We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE. Results Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (n = 4), blaKPC-2 (n = 3), blaIMP (n = 2), and blaNDM-1 (n = 1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%–26%). Conclusions We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.

During the COVID-19 pandemic, distinguishing dengue from cases of COVID-19 in endemic areas can be difficult. In a tertiary hospital contending with COVID-19 during a dengue epidemic, a triage strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. All febrile patients with viral prodromes and no epidemiologic risk for COVID-19 were first admitted to a designated ward for COVID-19 testing, where enhanced personal protective equipment was used by healthcare workers until COVID-19 was ruled out. From January to May 2020, 11,086 admissions were screened for COVID-19; 868 cases of COVID-19 were diagnosed in our institution, along with 380 cases of dengue. Only 8.5% (943/11,086) of suspected COVID-19 cases were concurrently tested for dengue serology due to a compatible overlapping clinical syndrome, and dengue was established as an alternative diagnosis in 2% (207/10,218) of suspected COVID-19 cases that tested negative. There were eight COVID-19 cases with likely false-positive dengue serology and one probable COVID-19/dengue coinfection. From April to May 2020, 251 admissions presenting as viral prodromes with no respiratory symptoms were screened; of those, 15 cases had COVID-19, and 2/15 had false-positive dengue IgM. Epidemiology investigations showed no healthcare-associated transmission. In a dengue epidemic season coinciding with a COVID-19 pandemic, dengue was established as an alternative diagnosis in a minority of COVID-19 suspects, likely due to early availability of basic diagnostics. Routine screening of patients with viral prodromes during a dual outbreak of COVID-19 and dengue enabled containment of COVID-19 cases masquerading as dengue with false-positive IgM.

Background: In the ongoing coronavirus disease 2019 (COVID-19) pandemic, resuming provision of surgical services poses a challenge given that patients may have acute surgical pathologies with concu...

Although gait variability has been linked to cognitive decline among older adults, the lack of a comprehensive composite gait variability score has dampened the application of gait variability.Does the enhanced gait variability index (EGVI) - a composite score gait variability index - provide differential and useful information on cognitive decline in community-dwelling adults from that using gait speed?Healthy community-dwelling adults (n = 311) aged 21-90 were individually administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Habitual gait speed and spatiotemporal parameters were measured using a 6 m instrumented walkway system. The EGVI for each participant was calculated from five spatiotemporal parameters - step length(cm), step time(s), stance time(s), single support time(s) and stride velocity(cm/s). Linear regression models, controlling for age, gender, and education, were built to examine the independent effects of EGVI or gait speed on global cognition and individual domains.Multiple regression revealed that gait speed contributed significantly to the performance of the domain "Attention" (p = 0.04) whereas EGVI contributed significantly for the performance of the domain "Visuospatial" (p = 0.04) and "Delayed Memory" (p = 0.02).EGVI provides differential and useful information from using gait speed alone. The EGVI may offer a solution to measure or track GV changes in relation to cognitive changes.

To observe the effect of conventional ovulation induction protocol and acupuncture combined with conventional ovulation induction protocol on pregnancy outcomes of frozen embryo transfer (FET) in patients with anovulatory infertility.A total of 60 patients with anovulatory infertility were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional ovulation induction protocol was applied to prepare endometrium. On the basis of the control group, acupuncture was started on the 2nd day of menstrual cycle in the observation group，Baihui (GV 20), Mingmen (GV 4), Geshu (BL 17), Guanyuan (CV 4), Qihai (CV 6), etc. were selected, once every other day, until 1 day before transplantation. The clinical pregnancy rate, embryo implantation rate, endometrial morphology on HCG trigger day, ovulation rate and cycle cancellation rate were compared in the two groups. The endometrial thickness before treatment and on HCG trigger day, TCM symptom score before and after treatment were observed in the two groups.In the observation group, the embryo implantation rate and clinical pregnancy rate were higher than the control group (On the basis of the conventional ovulation induction protocol, acupuncture could enhance the embryo implantation rate and clinical pregnancy rate of FET, improve the endometrial receptivity of patients with anovulatory infertility.

During this coronavirus disease 2019 (COVID-19) pandemic, physicians have the important task of risk stratifying patients who present with acute respiratory illnesses. Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections. Thus, identifying clinical features that are strongly associated with COVID-19 in comparison to other respiratory viruses can aid risk stratification and testing prioritization especially in situations where resources for virological testing and resources for isolation facilities are limited. In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups. In comparing outcomes, patients with COVID-19 were more likely to need high dependency or intensive care unit care and had a longer median length of stay. With our findings, we emphasize that epidemiological risk factors and clinical symptoms are more useful than laboratory and radiological abnormalities in differentiating COVID-19 from other respiratory viral infections.

Highlights • Cases of COVID-19 may be housed outside isolation wards prior to detection. • A bundle of infrastructural enhancements, improved PPE and social distancing was implemented. • Of 253 staff close-contacts and 45 patient close-contacts of 28 index cases, one patient contact tested positive. • Environmental sampling was positive for SARS-CoV-2 in 5 out of 28 cases. • An infection control bundle mitigated COVID-19 transmission in a general ward setting., Background During an ongoing outbreak of COVID-19, unsuspected cases may be housed outside of dedicated isolation wards. Aim At a Singaporean tertiary hospital, individuals with clinical syndromes compatible with COVID-19 but no epidemiologic risk were placed in cohorted general wards for COVID-19 testing. To mitigate risk, an infection control bundle was implemented comprising infrastructural enhancements, improved personal-protective-equipment (PPE), and social distancing. We assessed the impact on environmental contamination and transmission. Method Upon detection of a case of COVID-19 in the dedicated general ward, patients and healthcare workers (HCWs) contacts were identified. All patient and staff-close contacts were placed on 14-day phone surveillance and followed-up for 28 days; symptomatic contacts were tested. Environmental samples were also obtained. Findings Over a 3-month period, 28 unsuspected cases of COVID-19 were contained in the dedicated general ward. In 5 of the 28 cases, sampling of the patient's environment yielded SARS-CoV-2; index cases who required supplemental oxygen had higher odds of environmental contamination (p=0.01). A total of 253 staff close-contacts and 45 patient close-contacts were identified; only 3 HCWs (1.2%, 3/253) required quarantine. On 28-day follow-up, no patient-to-HCW transmission was documented; only one symptomatic patient close-contact tested positive. Conclusion Our institution successfully implemented an intervention bundle to mitigate COVID-19 transmission in a multi-bedded cohorted general ward setting.

Background We evaluated tuberculosis (TB) acquisition rate and risk factors among health care workers (HCWs) exposed to index TB patients. Methods We performed a retrospective cohort study on exposed HCWs from August 2016 to January 2018 at a tertiary hospital in Singapore. Demographic factors and TB exposure episodes per HCW were obtained. A modified Poisson regression model was used to identify factors associated with TB infection. Results A total of 32 TB exposure events occurred during the study period. A total of 881 HCWs with 1,536 exposure episodes were screened with QuantiFERON-TB Gold In-tube assay (QFT-GIT) at baseline and 8 weeks. A total of 129 (14.6%) HCWs had positive QFT-TB at baseline, whereas 22 (2.5%) HCWs had QFT-GIT conversion, with a latent TB infection (LTBI) rate of 1.14 cases per 100 exposure episodes per year. Foreign nationality, non-Chinese ethnicity, and age above 40 years were independently associated with baseline LTBI, whereas having >2 TB exposure episodes and working in internal medicine, medical subspecialties, and psychiatry wards were associated with QFT-GIT conversion. Discussion The QFT-GIT conversion rate among screened HCWs is low. Foreign HCWs with LTBI likely came from countries with higher TB transmission. Targeted prevention of repeated TB exposures can reduce QFT-GIT conversion. Conclusions The study results will guide TB contact tracing protocols in health care institutions.

With astonishing speed, COVID-19 has become a global pandemic. As it is uncertain when the pandemic will be controlled, it is crucial for procedurists of all stripes to be familiar and confident in performing procedures for COVID-19 patients to prevent intra-hospital infection. In this article, we will detail our approach on how to perform interventional procedures for COVID-19 patients at the bedside in the isolation room and with the patient transferred to the interventional radiology centre. These workflows have been developed in conjunction with multiple other stakeholders within our hospital, drawing from valuable lessons we have learnt from the SARS outbreak of 2003.

To perform meta-analysis to investigate the efficacy and safety of traditional Chinese medicine (TCM) compound in the treatment of endometriosis (EMS)-induced infertility.The databases of PubMed, Embase, Cochrane Library, Chinese Journal Full-text Database (CNKI), VIP, Wanfang Science and Technology Journal Full-text Database, and Chinese Biomedical Literature (CBM) were used to search for articles on the treatment of EMS-induced infertility with TCM compound from database establishment to September 2021. Endnote X9 software was used to screen the articles. Stata 15.1 and RevMan 5.3 software were used to record the data, and a meta-analysis was performed on the effective rate, pregnancy rate, abortion rate, incidence of adverse reactions, luteinizing hormone (LH) level, and estradiol (E2) level of TCM compound in the treatment of EMS-induced infertility. Finally, the reliability of the results was assessed by sensitivity analysis. A funnel plot was used to evaluate the publication bias of the articles.A total of 11 articles were included. Meta-analysis showed that when TCM compound was used to treat EMS-induced infertility, the effective rate of the trial group was significantly higher than that in the control group [odds ratio (OR) =1.26; 95% confidence interval (CI): 1.00 to 1.60; P=0.049], and the difference was statistically significant; the pregnancy rate of the trial group was significantly higher than that in the control group (OR =1.94; 95% CI: 1.50 to 2.50; P0.05), and the difference was statistically significant; the abortion rate of the trial group was significantly lower than that in the control group (OR =0.16; 95% CI: 0.06 to 0.48; P=0.01), and the difference was statistically significant; and the incidence of adverse reactions in the trial group was not significantly different from the control group (OR =0.48; 95% CI: 0.17 to 1.34; P=0.162); the LH level of the trial and control group [standardized mean difference (SMD) =0.51; 95% CI: -1.73 to 2.75; P=0.658], and the E2 level (SMD =1.65; 95% CI: -0.77 to 4.07; P=0.182) had no statistical difference.Chinese herbal compound is effective in the treatment of endometriotic infertility and has a positive effect on improving the pregnancy rate.

Objectives Since December 2019, COVID-19 has caused a worldwide pandemic and Singapore has seen escalating cases with community spread. Aggressive contact tracing and identification of suspects has helped to identify local community clusters, surveillance being the key to early intervention. Healthcare workers have contracted COVID-19 infection both at the workplace and community. We aimed to create a prototype staff surveillance system for the detection of acute respiratory infection (ARI) clusters amongst our healthcare workers (HCWs) and describe its effectiveness. Methods/Results A prototypical surveillance system was built on existing electronic health record infrastructure. Over a 10-week period, we investigated 10 ARI clusters amongst 7 departments. One of the ARI clusters was later determined to be related to COVID-19 infection. We demonstrate the feasibility of syndromic surveillance to detect ARI clusters during the COVID-19 outbreak. Conclusion The use of syndromic surveillance to detect ARI clusters amongst HCWs in the COVID-19 pandemic may enable early case detection and prevent onward transmission. It could be an important tool in infection prevention within healthcare institutions.

ObjectiveTo investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.MethodsA prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN).ResultsThere were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; pH. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV.ConclusionsWe suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

Cell manipulation is the foundation of biochemical studies, which demands user-friendly, multifunctional and precise tools. Based on flow confinement principles, open microfluidics can control the movement of microscale liquid in open space. Every position of the circuit is accessible to external instruments, making it possible to perform precise treatment and analysis of cells at arbitrary target positions especially at the single-cell/sub-cell level. Benefiting from its unique superiority, various manipulations including patterned cell culture, 3D tissue modelling, localized chemical stimulation, online cellular factor analysis, single cell sampling, partial cell treatment, and subcellular free radical attack can be easily realized. In this tutorial review, we summarize two basic ideas to design open microfluidics: open microfluidic networks and probes. The principles of mainstream open microfluidic methods are explained, and their recent important applications are introduced. Challenges and developing trends of open microfluidics are also discussed.

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the highly selective autoimmune injury of small intrahepatic bile ducts. Studies reported that the cholangiocytes from PBC patients expressed significantly higher levels of both receptor activator of nuclear factor-kappa B (RANK) and its ligand RANKL. However, the accurate role of RANK/RANKL axis in PBC remains unclear. Forty patients with PBC were enrolled according to the inclusion criteria. The biochemical parameters (alkaline phosphatase, ALP; gamma-glutamyltransferase, GGT; alanine aminotransferase, ALT; aspartate transaminase, AST; total bilirubin, TB) were collected at baseline and followed-up after 6 months of treatment with ursodeoxycholic acid (UDCA, 15 mg/kg d). Stages of PBC were diagnosed based on liver biopsy histopathology according to Nakanuma’s criteria. RANK expression in hepatic tissues was detected by immunohistochemistry. The cellular immunofluorescence method was used to locate the distribution of RANK in the human intrahepatic biliary epithelial cells (HIBECs) cultured in vitro. HIBECs were treated with RANKL at a concentration of 100 ng/ml or transfected with RANK-overexpressing lentivirus (LV-RANK). CCK-8 assay and cell cycle assay were used to detect the cell proliferation. Real-time PCR was used to detect the expression of IL-6, E-cadherin, VCAM, ICAM-1, TNF-α, and CD80. RANK expression in liver biopsies from early PBC patients (stage I + stage II) was significantly lower than that from advanced PBC patients (stage III + stage IV) (1.7 ± 0.63 vs. 2.3 ± 0.45 scores, P

Professor介绍陈贵珍教授针灸治疗围绝经期惊恐障碍的经验。陈教授认为围绝经期惊恐障碍的病因病机乃先天肾精渐亏，后天脾胃受损，终致脑窍失养，神机失用。临床治疗应以“滋先天，补后天，通督益髓，调理冲任”为原则。临证选穴重视俞募相配；针法讲究飞针速刺，巧施穴位埋线；针药结合，相得益彰；以情胜情，身心同治。提倡“一针、二线、三药、四情”综合治疗围绝经期惊恐障碍。.

Introduction Surgical site infections (SSIs) are a significant source of morbidity and mortality in the Asia–Pacific region (APAC), adversely impacting patient quality of life, fiscal productivity and placing a major economic burden on the country’s healthcare system. This commentary reports the findings of a two-day meeting that was held in Singapore on July 30–31, 2019, where a series of consensus recommendations were developed by an expert panel composed of infection control, surgical and quality experts from APAC nations in an effort to develop an evidence-based pathway to improving surgical patient outcomes in APAC. Methods The expert panel conducted a literature review targeting four sentinel areas within the APAC region: national and societal guidelines, implementation strategies, postoperative surveillance and clinical outcomes. The panel formulated a series of key questions regarding APAC-specific challenges and opportunities for SSI prevention. Results The expert panel identified several challenges for mitigating SSIs in APAC; (a) constraints on human resources, (b) lack of adequate policies and procedures, (c) lack of a strong safety culture, (d) limitation in funding resources, (e) environmental and geographic challenges, (f) cultural diversity, (g) poor patient awareness and (h) limitation in self-responsibility. Corrective strategies for guideline implementation in APAC were proposed that included: (a) institutional ownership of infection prevention strategies, (b) perform baseline assessments, (c) review evidence-based practices within the local context, (d) develop a plan for guideline implementation, (e) assess outcome and stakeholder feedback, and (f) ensure long-term sustainability. Conclusions Reducing the risk of SSIs in APAC region will require: (a) ongoing consultation and collaboration among stakeholders with a high level of clinical staff engagement and (b) a strong institutional and national commitment to alleviate the burden of SSIs by embracing a safety culture and accountability.

Background Periprosthetic joint infection (PJI) is a catastrophic complication after total hip arthroplasty (THA). Our meta-analysis aimed to identify the individual-related risk factors that predispose patients to PJI following primary THA. Methods Comprehensive literature retrieval from Pubmed, Web of Science, and the Cochrane Library was performed from inception to Feb 20th, 2021. Patient-related risk factors were compared as per the modifiable factors (BMI, smoke and alcohol abuse), non-modifiable factors (gender, age), and medical history characteristics, such as diabetes mellitus (DM), avascular necrosis (AVN) of femoral head, femoral neck fracture, rheumatoid arthritis (RA), cardiovascular disease (CVD), and osteoarthritis (OA) etc. The meta-analysis was applied by using risk ratios with 95% corresponding intervals. Sensitivity analysis and publication bias were performed to further assess the credibility of the results. Results Overall, 40 studies with 3,561,446 hips were enrolled in our study. By implementing cumulative meta-analysis, higher BMI was found associated with markedly increased PJI risk after primary THA [2.40 (2.01–2.85)]. Meanwhile, medical characteristics including DM [1.64 (1.25–2.21)], AVN [1.65 (1.07–2.56)], femoral neck fracture [1.75 (1.39–2.20)], RA [1.37 (1.23–1.54)], CVD [1.34 (1.03–1.74)], chronic pulmonary disease (CPD) [1.22 (1.08–1.37)], neurological disease [1.19 (1.05–1.35)], opioid use [1.53 (1.35–1.73)] and iron-deficiency anemia (IDA) [1.15 (1.13–1.17)] were also significantly correlated with higher rate of PJI. Conversely, dysplasia or dislocation [0.65 (0.45–0.93)], and OA [0.70 (0.62–0.79)] were protective factors. Of Note, female gender was protective for PJI only after longer follow-up. Besides, age, smoking, alcohol abuse, previous joint surgery, renal disease, hypertension, cancer, steroid use and liver disease were not closely related with PJI risk. Conclusion Our finding suggested that the individual-related risk factors for PJI after primary THA included high BMI, DM, AVN, femoral neck fracture, RA, CVD, CPD, neurological disease, opioid use and IDA, while protective factors were female gender, dysplasia/ dislocation and OA.

Background Circular RNA PVT1 (circPVT1) is significantly upregulated in various human cancers and is related to poor clinical outcome of cancer patients. However, the prognostic and clinicopathological value of circPVT1 in diverse human cancers remains controversial and inconclusive. Aim The objective of our study is to evaluate the prognostic and clinicopathological role of circPVT1 for cancer patients. Methods and results PubMed, Embase, Web of Science, and Cochrane Library were searched for eligible studies by October 1, 2020. The correlation between circPVT1 expression, and overall survival (OS) and clinical parameters was assessed by pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses, heterogeneity, and publication bias were conducted to further enhance reliability. Twelve studies (1282 patients) were selected for this meta‐analysis, including 11 on prognosis and 10 on clinicopathological parameters. Elevated expression of circPVT1 was associated with a worse OS in cancer patients (HR, 2.009; 95% CI, 1.667‐2.408, 1.892; P

Background Surgical site infections (SSIs) represent a substantial clinical and economic burden on patients and the healthcare system. The prevention of SSIs entails surveillance activities which lead to effective mitigation strategies, which are lacking across Asia Pacific (APAC). This manuscript aims to document gaps and challenges across APAC that affect the undertaking of a successful SSI surveillance activities and to provide recommendations on overcoming such challenges. Methods A targeted literature review with relevance to APAC identified a series of salient points pertaining to SSI prevention guidelines, implementation, surveillance and outcomes, which was discussed in July 2019 at the APAC Surgical Site Infection Prevention Symposium. An expert panel, comprising eight multidisciplinary experts from APAC and the USA, subsequently amalgamated the key discussion points from the Symposium and their clinical experiences in developing this article. Results The barriers to implementing a successful and effective APAC SSI surveillance program were identified as: (a) lack of standardized definitions, reporting methodology and accountability, (b) lack of fiscal resources, (c) reporting variability and under-reporting, and (d) lack of safety culture. Implementing an effective surveillance program in APAC will require countries to develop a well-designed and robust surveillance plan and ensure adequate training for staffs involved. Conclusion To improve SSI prevention in the region, it is imperative to encourage implementation of national programs with standardized methodologies and accountabilities. An ongoing APAC information exchange, including data and methodologies, will enable continuous learning within the APAC region.

Female mosquitoes feed sequentially on carbohydrates (nectar) and proteins (blood) during each gonadotrophic cycle to become reproductively competent and effective disease vectors. Accordingly, metabolism is synchronized to support this reproductive cyclicity. However, regulatory pathways linking metabolism to reproductive cycles are not fully understood. Two key hormones, juvenile hormone (JH) and ecdysteroids (20-hydroxyecdysone, 20E, is the most active form) govern female mosquito reproduction. Aedes aegypti genome codes for eight insulin-like peptides (ILPs) that are critical for controlling metabolism. We examined the effects of the JH and 20E pathways on mosquito ILP expression to decipher regulation of metabolism in a reproducing female mosquito. Chromatin immunoprecipitation assays showed genomic interactions between ilp genes and the JH receptor, methoprene-tolerant, a transcription factor, Krüppel homolog 1 (Kr-h1), and two isoforms of the ecdysone response early gene, E74. The luciferase reporter assays showed that Kr-h1 activates ilps 2, 6, and 7, but represses ilps 4 and 5. The 20E pathway displayed the opposite effect in the regulation of ilps. E74B repressed ilps 2 and 6, while E74A activated ilps 4 and 5. Combining RNA interference, CRISPR gene tagging and enzyme-linked immunosorbent assay, we have shown that the JH and 20E regulate protein levels of all eight Ae. aegypti ILPs. Thus, we have established a regulatory axis between ILPs, JH, and 20E in coordination of metabolism during gonadotrophic cycles of Ae. aegypti.

Background. Long noncoding RNAs (lncRNAs) have critical regulatory functions in biological and pathological activities during osteosarcoma progression. It is important to elucidate the expression pattern and reveal the underlying mechanisms of the newly identified lncRNAs. Methods. Herein, we screened the differentially expressed lncRNAs in osteosarcoma tumors and cell lines using lncRNA microarray. The candidate lncRNA was further verified by qRT-PCR, and the association of gene expression with clinicopathological features was evaluated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The targeting miRNA was identified using starBase analysis, and the competing endogenous RNA (ceRNA) network was established by STRING. Overexpression and silence of RNA were detected by qRT-PCR. Osteosarcoma cell proliferation was measured with CCK-8 assay, and the migration and invasion were evaluated with Transwell assay. Colony formation assay was observed. Flow cytometry evaluated the cell cycle. Western blot was performed to detect the mitotic markers and apoptosis-related proteins. A nude mouse tumor formation experiment was used to evaluate osteosarcoma progression in vivo. Cooverexpressing miR-34b-3p with RAD51 reversed the miR-34b-3p-induced changes in proliferation, the cell cycle, the expression of H2A.X, and that of apoptosis-related proteins. Results. HCG9 was identified as osteosarcoma-associated lncRNA. Osteosarcoma tissues and cell lines expressed higher levels of HCG9 as compared to normal tissues and osteoblasts, and high expression of HCG9 was further proved to be related to metastasis and the grade of osteosarcoma in clinical cases. Knockdown of HCG9 inhibited the proliferation, migration, and invasion of osteosarcoma cells. miR-34b-3p was identified as the target of HCG9, and RAD51 acted as a potential target of miR-34b-3p. Cooverexpressing miR-34b-3p with HCG9 partially suppressed the HCG9-stimulated proliferation, migration, and invasion of osteosarcoma cells in vitro and delayed the tumor progression in vivo. Conclusion. We discovered that lncRNA HCG9 promoted the proliferation of osteosarcoma cells via suppressing miR-34b-3p. Our study provides novel biomarkers and potential therapeutic targets for osteosarcoma treatment.

Summary To determine the variation in practices on meticillin-resistant Staphylococcus aureus (MRSA) surveillance and management of MRSA-colonized patients amongst 17 acute healthcare facilities in Singapore, the Ministry of Health convened a sharing session with Infection Prevention and Control Leads. All hospitals practised close to universal MRSA entry swabbing in keeping with national policy. There were, however, major variations in the response to both positive and negative surveillance swabs across facilities including the role of routine antiseptic bathing and MRSA decolonization. Most undertaking decolonization considered its role to be in ‘bioburden reduction’ rather than longer-term clearance.

Background During the ongoing COVID-19 pandemic, healthcare-associated transmission of respiratory viral infections (RVI) is a concern. To reduce the impact of SARS-CoV-2 and other respiratory viruses on patients and healthcare workers (HCWs) we devised and evaluated a multi-tiered infection control strategy with the goal of preventing nosocomial transmission of SARS-CoV2 and other RVIs across a large healthcare campus. Methodology From January-June 2020, a multi-tiered infection control strategy was implemented across a healthcare campus in Singapore, comprising the largest acute tertiary hospital as well as four other subspecialty centres, with more than 10,000 HCWs. Drawing on our institution’s experience with an outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003, this strategy included improved patient segregation and distancing, and heightened infection prevention and control (IPC) measures including universal masking. All symptomatic patients were tested for COVID-19 and common RVIs. Results A total of 16,162 admissions campus-wide were screened; 7.% (1155/16162) tested positive for COVID-19. Less than 5% of COVID-19 cases (39/1155) were initially detected outside of isolation wards in multi-bedded cohorted wards. Improved distancing and enhanced IPC measures successfully mitigated onward spread even amongst COVID-19 cases detected outside of isolation. COVID-19 rates amongst HCWs were kept low (0.13%, 17/13066) and reflected community acquisition rather than nosocomial spread. Rates of healthcare-associated-RVI amongst inpatients fell to zero and this decrease was sustained even after the lifting of visitor restrictions. Conclusion This multi-tiered infection control strategies can be implemented at-scale to successfully mitigate healthcare-associated transmission of respiratory viral pathogens., Highlights • A multi-tiered infection control strategy successfully contained both COVID-19 and common respiratory viral infections throughout a large healthcare system over six months of surveillance. • Despite caring for >1500 COVID-19 cases, no patient-staff transmission occurred. • Rates of healthcare-associated respiratory viral infections fell to zero over a six-month period. • Key components of the strategy included improved patient segregation and distancing, and universal masking.