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BackgroundSocial prescribing (SP) enables healthcare professionals to link patients with non-medical interventions available in the community to address underlying socioeconomic and behavioural determinants. We synthesised the evidence to understand the effectiveness of SP for chronic disease prevention.MethodsA systematic literature search was conducted using five databases and two registries. Eligible studies included randomised controlled trials of SP among community-dwelling adults recruited from primary care or community setting, investigating any chronic disease risk factors defined by the WHO (behavioural factors: smoking, physical inactivity, unhealthy diet and excessive alcohol consumption; metabolic factors: raised blood pressure, overweight/obesity, hyperlipidaemia and hyperglycaemia). Random effect meta-analyses were performed at two time points: completion of intervention and follow-up after trial.ResultsWe identified nine reports from eight trials totalling 4621 participants. All studies evaluated SP exercise interventions which were highly heterogeneous regarding the content, duration, frequency and length of follow-up. Majority of studies had some concerns for risk of bias. Meta-analysis revealed that SP likely increased physical activity (completion: mean difference (MD) 21 min/week, 95% CI 3 to 39, I2=0%; follow-up ≤12 months: MD 19 min/week, 95% CI 8 to 29, I2=0%). However, SP may not improve markers of adiposity, blood pressure, glucose and serum lipid. There were no eligible studies that primarily target unhealthy diet, smoking and excessive alcohol drinking behaviours.ConclusionsSP exercise interventions probably increased physical activity slightly; however, no benefits were observed for metabolic factors. Determining whether SP is effective in modifying the determinants of chronic diseases and promotes sustainable healthy behaviours is limited by the current evidence of quantification and uncertainty, warranting further rigorous studies.PROSPERO registration numberCRD42022346687.

Objective:To characterize the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and carbapenemase-producing Enterobacterales (CPE) co-colonization and to compare risk factors between healthcare facility types.Design, setting, and participants:We conducted a 3-year cross-sectional study among patients admitted to an acute-care hospital (ACH) and its 6 closely affiliated intermediate- and long-term care facilities (ILTCFs) in Singapore in June and July of 2014–2016.Methods:Specimens were concurrently collected from nares, axillae, and groins for MRSA detection, and from rectum or stool for VRE and CPE detection. Co-colonization was defined as having >1 positive culture of MRSA/VRE/CPE. Multinomial logistic regression was performed to determine predictors of co-colonization.Results:Of 5,456 patients recruited, 176 (3.2%) were co-colonized, with higher prevalence among patients in ITCFs (53 of 1,255, 4.2%) and the ACH (120 of 3,044, 3.9%) than LTCFs (3 of 1,157, 0.3%). MRSA/VRE was the most common type of co-colonization (162 of 5,456, 3.0%). Independent risk factors for co-colonization included male sex (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.37–2.80), prior antibiotic therapy of 1–3 days (OR, 10.39; 95% CI, 2.08–51.96), 4–7 days (OR, 4.89; 95% CI, 1.01–23.68), >7 days (OR, 11.72; 95% CI, 2.81–48.85), and having an open wound (OR, 2.34; 95% CI, 1.66–3.29). Additionally, we detected the synergistic interaction of length of stay >14 days and prior multidrug-resistant organism (MDRO) carriage on co-colonization. Having an emergency surgery was a significant predictor of co-colonization in ACH patients, and we detected a dose–response association between duration of antibiotic therapy and co-colonization in ILTCF patients.Conclusions:We observed common and differential risk factors for MDRO co-colonization across healthcare settings. This study has identified at-risk groups that merit intensive interventions, particularly patients with prior MDRO carriage and longer length of stay.

Introduction: There are limited studies exploring functional improvement in relation to characteristics of patients who, following acute hospital care, receive inpatient rehabilitation in community hospitals. We evaluated the association of acute hospital admission-related factors with functional improvement on community hospital discharge. Methods: We conducted a retrospective cohort study among patients who were transferred to community hospitals within 14-day post-discharge from acute hospital between 2016 and 2018. Modified Barthel Index (MBI) on a 100-point ordinal scale was used to assess functional status on admission to and discharge from the community hospital. We categorised MBI into 6 bands: 0–24, 25–49, 50–74, 75–90, 91–99 and 100. Multivariable logistic regression models were constructed to determine factors associated with categorical improvement in functional status, defined as an increase in at least one MBI band between admission and discharge. Results: A total of 5,641 patients (median age 77 years, interquartile range 69–84; 44.2% men) were included for analysis. After adjusting for potential confounders, factors associated with functional improvement were younger age, a higher MBI on admission, and musculoskeletal diagnosis for the acute hospital admission episode. In contrast, a history of dementia or stroke; lower estimated glomerular filtration rate; abnormal serum albumin or anaemia measured during the acute hospital episode; and diagnoses of stroke, cardiac disease, malignancy, falls or pneumonia; and other chronic respiratory diseases were associated with lower odds of functional improvement. Conclusion: Clinicians may want to take into account the presence of these high-risk factors in their patients when planning rehabilitation programmes, in order to maximise the likelihood of functional improvement. Keywords: Barthel Index, community hospitals, functional status, inpatients, rehabilitation, risk factors

Background Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV-2) and first reported in Wuhan, China, in December 2019. Since the severe acute respiratory syndrome (SARS) outbreak in 2003, Tan Tock Seng Hospital (TTSH) in Singapore has routinely fit-tested staff for high-filtration N95 respirators and established Web-based staff surveillance systems. The routine systems were enhanced in response to Singapore’s first imported COVID-19 case on 23 January 2020. Methods We conducted a cross-sectional study from 23 January to 23 February 2020 among healthcare workers to evaluate the effectiveness of the staff protection and surveillance strategy in TTSH, a 1600-bed multidisciplinary acute-care hospital colocated with the 330-bed National Centre for Infectious Diseases (NCID). As of 23 February 2020, TTSH/NCID has managed 76% of confirmed COVID-19 cases in Singapore. The hospital adopted a multipronged approach to protect and monitor staff with potential COVID-19 exposures: (1) risk-based personal protective equipment, (2) staff fever and sickness surveillance, and (3) enhanced medical surveillance of unwell staff. Results A total of 10 583 staff were placed on hospitalwide fever and sickness surveillance, with 1524 frontline staff working in COVID-19 areas under close surveillance. Among frontline staff, a median of 8 staff illness episodes was seen per day; almost 10% (n = 29) resulted in hospitalization. None of the staff was found to be infected with COVID-19. Conclusions A robust staff protection and health surveillance system that is routinely implemented during non–outbreak periods and enhanced during the COVID-19 outbreak is effective in protecting frontline staff from the infection.

Current descriptive epidemiological information on classic myeloproliferative neoplasms (MPNs) is incomplete. Published data among Asian population are particularly sparse.We conducted a large population-based study to determine the incidence rates and survival patterns of MPN reported to the Singapore Cancer Registry during the period 1968-2017. Age-standardised incidence rates(ASR), overall survival, 5-/10-year relative survival ratio (RSR) were estimated. Joinpoint regression was used to evaluate quinquennial percent change (QPC) in incidence.We identified 2557 individuals diagnosed with MPN including 1031 chronic myeloid leukaemia (CML), 424 polycythaemia vera (PV), 389 essential thrombocythaemia (ET), 134 primary myelofibrosis (PMF) and 579 MPN unclassifiable (MPN-U). The overall respective ASRs per 100,000 for CML, PV, ET, PMF and MPN-U were 1.24, 1.15, 1.07, 0.43, and 0.80 in 2013-2017. Males had higher ASR than females in all MPNs. A gradual rise in incidence trends of CML was observed between 1968 and 2017 (QPC 2.1%, 95% CI -0.9, 5.3). The overall incidence trends of non-CML MPNs including PV (QPC 62.9%, 95% CI 19.3, 122.6), ET (QPC 54.2%, 95% CI 23.5, 92.3) and PMF (QPC 103.5%, 95% CI 19.1, 247.6) increased sharply during 1993-2017. Survival was lower in MPNs compared with expected survival in general population: 5-year RSRs were 0.82 (95% CI 0.78, 0.86), 0.96 (95% CI 0.91, 1.01), 0.96 (95% CI 0.92, 1.01), 0.53 (95% CI 0.43, 0.65), and 0.74 (95% CI 0.68, 0.80) for CML, PV, ET, PMF and MPN-U respectively.CML incidence has increased marginally, whereas non-CML MPNs incidences have sharply increased. MPN patients have a lower relative survival compared to the general population, and patients with PV and ET have the most favourable relative survival. Median survival for CML patients has increased dramatically over the last 50 years.

Funding: Bioinformatics and Computational Biology analyses were supported by the University of St Andrews Bioinformatics Unit that is funded by a Wellcome Trust ISSF award (grant 097831/Z/11/Z). M.T.G.H is supported by the Scottish Infection Research Network and Chief Scientist Office through the Scottish Healthcare Associated Infection Prevention Institute consortium funding (CSO Reference: SIRN10). Objectives Methicillin-resistant Staphylococcus aureus(MRSA) has spread across countries and healthcare settings, with different ecological niches for different clones. It is crucial to understand the comparative epidemiology of MRSA clones between healthcare settings, and independent factors associated with colonization of specific clones. Methods We conducted annual cross-sectional surveillance studies in a network comprising an acute-care hospital and six closely-affiliated intermediate- and long-term care facilities in Singapore, in June-July, 2014-2016. 5,394 patients contributed 16,045 nasal, axillary and groin samples for culture and MRSA isolates for whole genome sequencing. Multivariable multilevel multinomial regression models were constructed to assess for independent factors associated with MRSA colonization. Results MRSA clonal complex(CC) 22 was more prevalent in the acute-care hospital(n=256/493; 51.9%) and intermediate-care(n=348/634; 54.9%) than long-term care(n=88/351; 25.1%) facilities, with clones besides CC22 and CC45 being more prevalent in long-term care facilities(n=144/351; 41.0%) (P

Thrombocytopenia commonly occurs in dengue and may be complicated by bleeding. Dengue can occur in adults who may be on long term antiplatelet therapy for ischemic heart disease or stroke. In these cases, clinicians may temporarily discontinue antiplatelet therapy to minimize the risk of bleeding in the absence of clear guidelines. We conducted a retrospective cohort study of laboratory-confirmed adult dengue patients on antiplatelet therapy and evaluated participants whose antiplatelet therapy was continued versus discontinued. Primary outcome was a composite outcome of major adverse cardiac and cerebrovascular events (MACCE), and all-cause mortality in-hospital and for 1-year post discharge. Secondary outcomes were platelet and blood transfusion, and occurrence of dengue haemorrhagic fever (DHF), dengue shock syndrome, dengue with warning signs and severe dengue according to World Health Organization criteria. Discontinuation of antiplatelet therapy did not result in higher composite outcome (p=0.192). Continuation of antiplatelet therapy did not result in more platelet or blood transfusion (p=0.489 and p=0.567 respectively), DHF (p=0.923). Our results suggest that discontinuation or continuation of antiplatelet therapy based on clinical judgement in dengue with thrombocytopenia, is largely safe but further studies are needed.

Current knowledge of methicillin-resistant Staphylococcus aureus (MRSA) colonisation in relation to epidemiological characteristics is incomplete. We conducted a cross-sectional study at an acute-care tertiary infectious diseases hospital of MRSA isolates identified through routine surveillance from January 2009 to December 2011. We randomly selected 205 MRSA isolates (119 inpatients) from 798 isolates (427 inpatients) for molecular profiling using multilocus sequence typing. Multilevel multinomial logistic regression was used to estimate odds ratio (OR) assessing the predilection of MRSA strains for anatomic sites, and associations of strains with human immunodeficiency virus (HIV) infection. The most frequent sequence types (STs) were 239, 22 and 45. The proportion of ST22 increased over the sampling period, replacing ST239 as the dominant lineage. However, ST239 remained the most prevalent among HIV-seropositive individuals who were six times more likely to be colonised with this strain than non-HIV patients (adjusted OR (aOR) 6.44, 95% confidence interval (CI) 1.94–21.36). ST45 was >24 times more likely to be associated with perianal colonisation than in the nares, axillae and groin sites (aOR 24.20, 95% CI 1.45–403.26). This study underlines the clonal replacement of MRSA in Singapore as previously reported but revealed, in addition, key strain differences between HIV-infected and non-infected individuals hospitalised in the same environment. This research received no specific grant from any funding agency, commercial or not-for-profit sectors.

Background: The risk factors for methicillin-resistant Staphylococcus aureus (MRSA) colonization can differ between acute-care, subacute-care, and long-term care facilities, but comparative information is lacking. We compared risk factors for MRSA colonization contemporaneously between an acute-care hospital (ACH) and its affiliated intermediate- and long-term care facilities (ILTCFs). Methods: Serial cross-sectional studies were conducted in a 1,600-bed tertiary-care ACH and its 6 affiliated ILTCFs in Singapore, in June–July 2014–2016. Separate nasal, axillary, and groin swabs were taken and cultured for MRSA. MRSA isolates were subject to whole-genome sequencing. Clinical and epidemiological data were obtained from medical records. To account for clustering, multivariable 2-level multinomial logistic regression models were constructed to assess factors associated with colonization of specific MRSA clones, in the ACH and ILTCFs, respectively. Results: In total, 8,873 samples from 2,985 patients in the ACH and 7,172 samples from 2,409 patients and residents in ILTCFs were included in the study. Patients and residents in the ILTCFs (29.7%) were more likely to be colonized with MRSA than patients in the ACH (12.6%) (P < .0001). The predominant MRSA clones were clonal complexes (CC)22 (n = 692, 46.7%) and CC45 (n = 494, 33.4%), contributing to 80% of MRSA isolates. For ACH patients, after adjusting for age, gender, comorbidities, prior exposures to antibiotics and percutaneous devices, presence of wounds, and screening year, prior MRSA carriage in the preceding 12 months was the strongest predictor of colonization with all MRSA clones: CC22 (aOR, 14.71; 95% CI, 6.17–34.48); CC45 (aOR, 7.75; 95% CI, 2.70–22.22); and others (aOR, 22.22; 95% CI, 3.83–125.00). Hospital stay >14 days was also positively associated with colonization with MRSA CC22 (aOR, 2.67; 95% CI, 1.22–5.88), but not the other clones. For ILTCF patients and residents, after adjusting for age, comorbidities, prior exposure to antibiotics, presence of wounds, and screening year, prior MRSA carriage was a significant predictor of colonization with MRSA CC22 (aOR, 2.72; 95% CI, 1.35–5.46), and CC45 (aOR, 2.36; 95 % CI, 1.06–5.24), but not with other clones. Additionally, prior exposure to a percutaneous device and being male were respectively positively associated with colonization by MRSA CC22 (aOR, 2.70; 95% CI, 1.19–6.17) and CC45 (aOR, 2.17; 95% CI, 1.11–4.26). Conclusions: Prior MRSA carriage was a common risk factor for colonization with the predominant MRSA clones in both the ACH and ILTCFs. Hospital stay >14 days and exposure to percutaneous devices were additional risk factors for CC22 colonization in the ACH and ILTCFs, respectively. Pre-emptive contact precautions for prior MRSA-carriers on admission and active screening for long-stayers in the ACH could prevent intra- and interinstitutional MRSA transmission.Funding: NoneDisclosures: None

Funding: This research was supported by the Small Innovative Grant (SIG/15033) and Communicable Diseases – Public Health Research Grant (CDPHRG/0008/2014) awarded by the National Healthcare Group and Ministry of Health Singapore respectively. Objectives With the widespread use of antiseptics in healthcare facilities for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) transmission, there are concerns for antiseptic tolerance and resistance. We sought to understand the use of chlorhexidine and octenidine, qac genes carriage and reduced antiseptic susceptibilities. Methods A serial cross-sectional study was conducted in an acute care hospital and three extended-care facilities of a healthcare network in June-July, 2014-2016. Two of the extended-care facilities were exposed to intranasal octenidine and universal daily chlorhexidine/octenidine bathing. The minimum inhibitory concentration (MIC) levels and qac genes were determined by broth microdilution tests and whole genome sequencing respectively. Multivariable logistic regression was used to assess for the independent associations between antiseptic exposures, qac genes and reduced antiseptic susceptibilities. Results A total of 878 MRSA isolates were obtained. There were associations between qacA/B carriage and chlorhexidine (adjusted odds ratio [aOR]: 7.80; 95% confidence interval [CI]: 3.25-18.71) and octenidine (aOR: 11.79; 95%CI: 5.14-27.04) exposures. Chlorhexidine exposure was associated with reduced chlorhexidine susceptibility (MIC≥4mg/L) (aOR: 3.15; 95%CI: 1.14-8.74). Carriage of qacA/B (aOR: 10.65: 95%CI: 4.14-27.40) or qacC (aOR: 2.55; 95%CI: 1.22-5.32) had an association with reduced chlorhexidine susceptibility; while MRSA sequence type modified the association. However, we found no direct association between (i) antiseptics use and qacC carriage, (ii) octenidine exposure and reduced susceptibility and (iii) reduced octenidine susceptibility and qacA/B or qacC carriage. Conclusions Antiseptic exposures were associated with qac genes carriage. Chlorhexidine exposure was associated with reduced chlorhexidine susceptibility, requiring continued surveillance for the emergence of resistance. Postprint

Multiple in vitro and mice model studies suggest statins may attenuate dengue severity. However, little is known about statin use and dengue severity in adult dengue patients with hyperlipidemia. We conducted a retrospective cohort study from 2004–2008 and 2012–2013 in Tan Tock Seng Hospital, Singapore on adult dengue patients with hyperlipidemia, comparing those with and without statin usage at hospitalization in terms of primary outcome of dengue hemorrhagic fever (DHF) or shock syndrome (DSS), and severe dengue (SD). Of 13,975 subjects screened, 257 dengue patients were included; 191 (74.3%) were statin users and 66 (25.7%) were non-users. Compared with non-users, statin use was not associated with decreased risk of DHF/DSS (adjusted risk ratio [aRR] = 0.66, 95%confidence interval [CI]: 0.41–1.08, P = 0.10) and SD (aRR = 1.43, 95%CI: 0.84–2.43, P = 0.19). Therefore, statin usage had minimal effect on dengue severity in our study population in Singapore.

Vancomycin-resistant enterococci (VRE) are an important cause of nosocomial infections in acute-care hospitals (ACHs), intermediate-care facilities (ITCFs), and long-term care facilities (LTCFs). This study contemporaneously compared the epidemiology and risk factors for VRE colonization in different care settings in a health care network. We conducted a serial cross-sectional study in a 1,700-bed ACH and its six closely affiliated ITCFs and LTCFs in June and July of 2014 to 2016. Rectal swab or stool specimens were cultured for VRE. Multivariable logistic regression was used to assess for independent risk factors associated with VRE colonization. Of 5,357 participants, 523 (9.8%) were VRE colonized. VRE prevalence was higher in ACHs (14.2%) than in ITCFs (7.6%) and LTCFs (0.8%). Common risk factors between ACHs and ITCFs included prior VRE carriage, a longer duration of antibiotic therapy, surgery in the preceding 90 days, and the presence of a skin ulcer. Independent risk factors specific to ACH-admitted patients were prior methicillin-resistant Staphylococcus aureus carriage, a higher number of beds per room, prior proton pump inhibitor use, and a length of stay of >14 days. For ITCFs, a length of stay of >14 days was inversely associated with VRE colonization. Similarities and differences in risk factors for VRE colonization were observed between health care settings. VRE prevention efforts should target the respective high-risk patients. MOH (Min. of Health, S’pore) Published version

Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO 2009 criteria. Multivariable Poisson regression with robust error variance was used to estimate risk ratio (RR). Compared with non-use, metformin use was associated with a decreased risk of developing severe dengue (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI]: 0.37–0.98, P = 0.04). Additionally, there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49–0.98, P = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of metformin, however, was not associated with dengue severity based on WHO 1997 criteria; and no dose-response relationship was noted. Our results suggest metformin use could attenuate disease severity in dengue-infected diabetes mellitus individuals.